Raras
Buscar doenças, sintomas, genes...
Doença do metabolismo do folato
ORPHA:285657CID-11 · 5C63.1DOENÇA RARA

A riboflavina (lactoflavina ou vitamina B2; designada no passado também por vitamina G; nome sistemático 7,8 - dimetil-10-(D-1'-ribitil)-isoaloxazina) é um composto orgânico (flavina) da classe das vitaminas. No organismo humano, favorece o metabolismo das gorduras, açúcares e proteínas e é importante para a saúde dos olhos, pele, boca e cabelos.

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Introdução

O que você precisa saber de cara

📋

Doença rara que afeta o metabolismo e transporte do folato, causando retardo do crescimento, fraqueza muscular, imunodeficiência e glossite. Pode manifestar-se com hiperreflexia, infecções recorrentes e anormalidades motoras.

🏥
SUS: Cobertura mínimaScore: 20%
Centros em: PA, PR, SC, RS, ES +8
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Sinais e sintomas

O que aparece no corpo e com que frequência cada sintoma acontece

Partes do corpo afetadas

🧠
Neurológico
46 sintomas
🩸
Sangue
16 sintomas
🫃
Digestivo
7 sintomas
📏
Crescimento
6 sintomas
👁️
Olhos
5 sintomas
🦴
Ossos e articulações
4 sintomas

+ 63 sintomas em outras categorias

Características mais comuns

Retardo do crescimento pós-natal
Atrofia do músculo esquelético
Anormalidade do sistema imunológico
Hiperreflexia
Glossite
Infecções do trato urinário recorrentes
168sintomas
Sem dados (168)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 168 características clínicas mais associadas, ordenadas por frequência.

Retardo do crescimento pós-natalPostnatal growth retardation
Atrofia do músculo esqueléticoSkeletal muscle atrophy
Anormalidade do sistema imunológicoAbnormality of the immune system
HiperreflexiaHyperreflexia
GlossiteGlossitis

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa6
Últimos 10 anos200publicações
Pico202552 papers
Linha do tempo
20202020Hoje · 2026🧪 2022Primeiro ensaio clínico📈 2025Ano de pico
Publicações por ano (últimos 10 anos)

Encontrou um erro ou informação desatualizada? Sugira uma correção →

Genética e causas

O que está alterado no DNA e como passa nas famílias

Genes associados

7 genes identificados com associação a esta condição.

MTHFS5-formyltetrahydrofolate cyclo-ligaseDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Contributes to tetrahydrofolate metabolism. Helps regulate carbon flow through the folate-dependent one-carbon metabolic network that supplies carbon for the biosynthesis of purines, thymidine and amino acids. Catalyzes the irreversible conversion of 5-formyltetrahydrofolate (5-FTHF) to yield 5,10-methenyltetrahydrofolate

LOCALIZAÇÃO

Cytoplasm

VIAS BIOLÓGICAS (1)
Metabolism of folate and pterines
MECANISMO DE DOENÇA

Neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination

An autosomal recessive neurodevelopmental disorder with onset at birth or in early infancy, and characterized by microcephaly, short stature, severe global developmental delay, progressive spasticity, and epilepsy. Brain imaging shows delayed myelination, hypomyelination, enlarged ventricles, and cerebellar atrophy.

EXPRESSÃO TECIDUAL(Ubíquo)
Fígado
99.8 TPM
Sangue
36.5 TPM
Rim - Córtex
28.1 TPM
Pituitária
26.3 TPM
Tireoide
22.0 TPM
OUTRAS DOENÇAS (1)
neurodevelopmental disorder with microcephaly, epilepsy, and hypomyelination
HGNC:7437UniProt:P49914
FTCDFormimidoyltransferase-cyclodeaminaseDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Folate-dependent enzyme, that displays both transferase and deaminase activity. Serves to channel one-carbon units from formiminoglutamate to the folate pool Binds and promotes bundling of vimentin filaments originating from the Golgi

LOCALIZAÇÃO

Cytoplasm, cytosolGolgi apparatusCytoplasm, cytoskeleton, microtubule organizing center, centrosome, centriole

VIAS BIOLÓGICAS (1)
Histidine catabolism
MECANISMO DE DOENÇA

Glutamate formiminotransferase deficiency

Autosomal recessive disorder. Features of a severe phenotype, include elevated levels of formiminoglutamate (FIGLU) in the urine in response to histidine administration, megaloblastic anemia, and intellectual disability. Features of a mild phenotype include high urinary excretion of FIGLU in the absence of histidine administration, mild developmental delay, and no hematological abnormalities.

VIAS REACTOME (1)
EXPRESSÃO TECIDUAL(Ubíquo)
Fígado
281.4 TPM
Rim - Córtex
55.6 TPM
Testículo
31.5 TPM
Rim - Medula
19.8 TPM
Brain Caudate basal ganglia
7.0 TPM
OUTRAS DOENÇAS (1)
formiminoglutamic aciduria
HGNC:3974UniProt:O95954
DHFRDihydrofolate reductaseDisease-causing germline mutation(s) inModerado
FUNÇÃO

Catalyzes the reduction of 7,8-dihydrofolate (DHF) to 5,6,7,8-tetrahydrofolate in a NADPH-dependent manner (PubMed:12096917, PubMed:15039552, PubMed:17569517, PubMed:19196009, PubMed:19478082, PubMed:21876184, PubMed:9719595). Key enzyme in folate metabolism. Contributes to the nuclear and mitochondrial de novo thymidylate biosynthesis pathway (PubMed:21876188, PubMed:22235121). Catalyzes an essential reaction for de novo glycine and purine synthesis, and for DNA precursor synthesis. Binds its o

LOCALIZAÇÃO

MitochondrionCytoplasmNucleus

VIAS BIOLÓGICAS (3)
Tetrahydrobiopterin (BH4) synthesis, recycling, salvage and regulationMetabolism of folate and pterinesG1/S-Specific Transcription
MECANISMO DE DOENÇA

Megaloblastic anemia due to dihydrofolate reductase deficiency

An inborn error of metabolism, characterized by megaloblastic anemia and/or pancytopenia, severe cerebral folate deficiency, and cerebral tetrahydrobiopterin deficiency. Clinical features include variable neurologic symptoms, ranging from severe developmental delay and generalized seizures in infancy, to childhood absence epilepsy with learning difficulties, to lack of symptoms.

EXPRESSÃO TECIDUAL(Ubíquo)
Linfócitos
33.1 TPM
Fibroblastos
17.8 TPM
Brain Spinal cord cervical c-1
13.9 TPM
Testículo
11.5 TPM
Substância negra
7.5 TPM
OUTRAS DOENÇAS (1)
constitutional megaloblastic anemia with severe neurologic disease
HGNC:2861UniProt:P00374
FOLR1Folate receptor alphaDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Binds to folate and reduced folic acid derivatives and mediates delivery of 5-methyltetrahydrofolate and folate analogs into the interior of cells (PubMed:19074442, PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114, PubMed:8567728). Has high affinity for folate and folic acid analogs at neutral pH (PubMed:23851396, PubMed:23934049, PubMed:2527252, PubMed:8033114, PubMed:8567728). Exposure to slightly acidic pH after receptor endocytosis triggers a conformation change that strongly

LOCALIZAÇÃO

Cell membraneApical cell membraneBasolateral cell membraneSecretedCytoplasmic vesicleCytoplasmic vesicle, clathrin-coated vesicleEndosome

VIAS BIOLÓGICAS (1)
COPII-mediated vesicle transport
MECANISMO DE DOENÇA

Neurodegeneration due to cerebral folate transport deficiency

An autosomal recessive neurodegenerative disorder resulting from brain-specific folate deficiency early in life. Onset is apparent in late infancy with severe developmental regression, movement disturbances, epilepsy and leukodystrophy.

EXPRESSÃO TECIDUAL(Tecido-específico)
Pulmão
102.8 TPM
Glândula salivar
72.4 TPM
Rim - Córtex
49.4 TPM
Rim - Medula
47.7 TPM
Tireoide
32.7 TPM
OUTRAS DOENÇAS (1)
neurodegenerative syndrome due to cerebral folate transport deficiency
HGNC:3791UniProt:P15328
MTHFRMethylenetetrahydrofolate reductase (NADPH)Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine (PubMed:29891918). Represents a key regulatory connection between the folate and methionine cycles (Probable)

LOCALIZAÇÃO

VIAS BIOLÓGICAS (1)
Metabolism of folate and pterines
MECANISMO DE DOENÇA

Homocystinuria due to deficiency of N(5,10)-methylenetetrahydrofolate reductase activity

An autosomal recessive inborn error of folate metabolism. Clinical severity is variable, ranging from severe neurologic features to absence of symptoms. Clinical features include homocysteinuria, homocysteinemia, developmental delay, severe intellectual disability, perinatal death, psychiatric disturbances, and later-onset neurodegenerative disorders.

EXPRESSÃO TECIDUAL(Ubíquo)
Ovário
25.6 TPM
Nervo tibial
24.0 TPM
Pulmão
21.5 TPM
Baço
21.4 TPM
Tireoide
20.6 TPM
OUTRAS DOENÇAS (6)
homocystinuria due to methylene tetrahydrofolate reductase deficiencyisolated anencephalyisolated exencephalyneural tube defects, folate-sensitive
HGNC:7436UniProt:P42898
SLC46A1Proton-coupled folate transporterDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Proton-coupled folate symporter that mediates folate absorption using an H(+) gradient as a driving force (PubMed:17129779, PubMed:17446347, PubMed:17475902, PubMed:19389703, PubMed:19762432, PubMed:25504888, PubMed:29344585, PubMed:30858177, PubMed:31494288, PubMed:31792273, PubMed:32893190, PubMed:34619546). Involved in the intestinal absorption of folates at the brush-border membrane of the proximal jejunum, and the transport from blood to cerebrospinal fluid across the choroid plexus (PubMed

LOCALIZAÇÃO

Cell membraneApical cell membraneBasolateral cell membraneEndosome membraneCytoplasm

VIAS BIOLÓGICAS (3)
Metabolism of folate and pterinesHeme signalingIron uptake and transport
MECANISMO DE DOENÇA

Hereditary folate malabsorption

Rare autosomal recessive disorder characterized by impaired intestinal folate absorption with folate deficiency resulting in anemia, hypoimmunoglobulinemia with recurrent infections, and recurrent or chronic diarrhea. In many patients, neurological abnormalities such as seizures or intellectual disability become apparent during early childhood, attributed to impaired transport of folates into the central nervous system. When diagnosed early, the disorder can be treated by administration of folate. If untreated, it can be fatal and, if treatment is delayed, the neurological defects can become permanent.

EXPRESSÃO TECIDUAL(Ubíquo)
Glândula adrenal
18.7 TPM
Cerebelo
15.0 TPM
Pituitária
15.0 TPM
Cérebro - Hemisfério cerebelar
14.7 TPM
Fígado
12.1 TPM
OUTRAS DOENÇAS (1)
hereditary folate malabsorption
HGNC:30521UniProt:Q96NT5
SLC19A1Reduced folate transporterDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Antiporter that mediates the import of reduced folates or a subset of cyclic dinucleotides, driven by the export of organic anions (PubMed:10787414, PubMed:15337749, PubMed:16115875, PubMed:22554803, PubMed:31126740, PubMed:31511694, PubMed:32276275, PubMed:36071163, PubMed:36265513, PubMed:36575193, PubMed:7826387, PubMed:9041240). Acts as an importer of immunoreactive cyclic dinucleotides, such as cyclic GMP-AMP (2'-3'-cGAMP), an immune messenger produced in response to DNA virus in the cytoso

LOCALIZAÇÃO

Cell membraneApical cell membraneBasolateral cell membrane

VIAS BIOLÓGICAS (1)
Metabolism of folate and pterines
MECANISMO DE DOENÇA

Megaloblastic anemia, folate-responsive

An autosomal recessive metabolic disorder characterized by megaloblastic anemia resulting from decreased folate transport into erythrocytes. Disease manifestations include hemolytic anemia, hyperhomocysteinemia, and low vitamin B12. Serum folate levels are normal, but erythrocyte folate levels are decreased. Treatment with oral folate corrects the anemia and normalizes homocysteine.

EXPRESSÃO TECIDUAL(Ubíquo)
Sangue
19.6 TPM
Pulmão
13.1 TPM
Cervix Ectocervix
12.7 TPM
Ovário
12.3 TPM
Baço
12.0 TPM
OUTRAS DOENÇAS (2)
immunodeficiency 114, folate-responsivemegaloblastic anemia, folate-responsive
HGNC:HGNC:10937UniProt:P41440

Variantes genéticas (ClinVar)

289 variantes patogênicas registradas no ClinVar.

🧬 MTHFS: GRCh37/hg19 15q24.1-26.3(chr15:73506509-102429112)x3 ()
🧬 MTHFS: GRCh37/hg19 15q24.1-25.2(chr15:74979036-81960184)x1 ()
🧬 MTHFS: NM_006441.4(MTHFS):c.9_18dup (p.Ser7fs) ()
🧬 MTHFS: NM_006441.4(MTHFS):c.10_25dup (p.Ala9fs) ()
🧬 MTHFS: GRCh37/hg19 15q24.1-26.3(chr15:75165490-102520892)x3 ()
Ver todas no ClinVar

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Onde tratar no SUS

Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)

🇧🇷 Atendimento SUS — Doença do metabolismo do folato

Centros de Referência SUS

21 centros habilitados pelo SUS para Doença do metabolismo do folato

Centros para Doença do metabolismo do folato

Detalhes dos centros

Hospital Universitário Prof. Edgard Santos (HUPES)

R. Dr. Augusto Viana, s/n - Canela, Salvador - BA, 40110-060 · CNES 0003808

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do Metabolismo

Hospital de Apoio de Brasília (HAB)

AENW 3 Lote A Setor Noroeste - Plano Piloto, Brasília - DF, 70684-831 · CNES 0010456

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital Estadual Infantil e Maternidade Alzir Bernardino Alves (HIABA)

Av. Min. Salgado Filho, 918 - Soteco, Vila Velha - ES, 29106-010 · CNES 6631207

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital das Clínicas da UFG

Rua 235 QD. 68 Lote Área, Nº 285, s/nº - Setor Leste Universitário, Goiânia - GO, 74605-050 · CNES 2338424

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do Metabolismo

Hospital das Clínicas da UFMG

Av. Prof. Alfredo Balena, 110 - Santa Efigênia, Belo Horizonte - MG, 30130-100 · CNES 2280167

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

NUPAD / Faculdade de Medicina UFMG

Av. Prof. Alfredo Balena, 189 - 5 andar - Centro, Belo Horizonte - MG, 30130-100 · CNES 2183226

Serviço de Referência

Rota
Erros Inatos do Metabolismo

Hospital Universitário João de Barros Barreto

R. dos Mundurucus, 4487 - Guamá, Belém - PA, 66073-000 · CNES 2337878

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital de Clínicas da Universidade Federal de Pernambuco

Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife - PE, 50670-901 · CNES 2561492

Atenção Especializada

Rota
Erros Inatos do Metabolismo

Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)

R. dos Coelhos, 300 - Boa Vista, Recife - PE, 50070-902 · CNES 0000647

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital de Clínicas da UFPR

R. Gen. Carneiro, 181 - Alto da Glória, Curitiba - PR, 80060-900 · CNES 2364980

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital Universitário Pedro Ernesto (HUPE-UERJ)

Blvd. 28 de Setembro, 77 - Vila Isabel, Rio de Janeiro - RJ, 20551-030 · CNES 2280221

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do Metabolismo

Instituto Nacional de Saúde da Mulher, da Criança e do Adolescente Fernandes Figueira (IFF/Fiocruz)

Av. Rui Barbosa, 716 - Flamengo, Rio de Janeiro - RJ, 22250-020 · CNES 2269988

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital Universitário Onofre Lopes (HUOL)

Av. Nilo Peçanha, 620 - Petrópolis, Natal - RN, 59012-300 · CNES 2408570

Atenção Especializada

Rota
Erros Inatos do Metabolismo

Hospital São Lucas da PUCRS

Av. Ipiranga, 6690 - Jardim Botânico, Porto Alegre - RS, 90610-000 · CNES 2232928

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do Metabolismo

Hospital de Clínicas de Porto Alegre (HCPA)

Rua Ramiro Barcelos, 2350 Bloco A - Av. Protásio Alves, 211 - Bloco B e C - Santa Cecília, Porto Alegre - RS, 90035-903 · CNES 2237601

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital Universitário da UFSC (HU-UFSC)

R. Profa. Maria Flora Pausewang - Trindade, Florianópolis - SC, 88036-800 · CNES 2560356

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do Metabolismo

Hospital das Clínicas da FMUSP

R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo - SP, 05403-010 · CNES 2077485

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital de Clínicas da UNICAMP

R. Vital Brasil, 251 - Cidade Universitária, Campinas - SP, 13083-888 · CNES 2748223

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Hospital de Clínicas de Ribeirão Preto (HCRP-USP)

R. Ten. Catão Roxo, 3900 - Vila Monte Alegre, Ribeirão Preto - SP, 14015-010 · CNES 2082187

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do MetabolismoDeficiência Intelectual

Instituto da Criança e do Adolescente (ICr-HCFMUSP)

Av. Dr. Enéas Carvalho de Aguiar, 647 - Cerqueira César, São Paulo - SP, 05403-000 · CNES 2081695

Serviço de Referência

Rota
Erros Inatos do Metabolismo

UNIFESP / Hospital São Paulo

R. Napoleão de Barros, 715 - Vila Clementino, São Paulo - SP, 04024-002 · CNES 2688689

Serviço de Referência

Rota
Anomalias CongênitasErros Inatos do Metabolismo
Sobre os centros SUS: Estes centros são habilitados pelo Ministério da Saúde como Serviços de Referência em Doenças Raras ou Serviços de Atenção Especializada. O atendimento é pelo SUS, com encaminhamento da rede de atenção básica.

Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.

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Publicações mais relevantes

🥉Melhor nível de evidência: Relato de caso
Timeline de publicações
0 papers (10 anos)
#1

SLC46A1 deficiency-mediated folate restriction suppresses colorectal cancer progression through epigenetic-transcriptional reprogramming.

Cell death & disease2026 Jan 31

The association between folate metabolism abnormalities and the development of colorectal cancer (CRC) remains controversial. Here, we report that the folate exerts a tumor-suppressive role in CRC; however, the manifestation of this effect is restricted by the expression level of folate transporter SLC46A1 in CRC cells. Multi-cohort profiling revealed significant downregulation of SLC46A1 in CRC tissues compared to adjacent normal tissues, where low expression independently predicted poor overall survival. Functional studies demonstrated that SLC46A1-mediated folate uptake suppressed tumor proliferation, migration, and invasion both in vitro and in vivo. Mechanistically, SLC46A1 deficiency restricted intracellular folate availability and impaired cellular methylation potential, as evidenced by a reduced SAM/SAH ratio, leading to DNA hypomethylation at specific sites such as the FOS proto-oncogene promoter. This epigenetic reprogramming triggers transcriptional activation of key oncogenic effectors CCND1, BCL2, and PLAU involved in CRC progression. Clinically, we found a significant inverse correlation between SLC46A1 expression and folate levels in tumor interstitial fluids of CRC, suggesting impaired folate uptake in low SLC46A1 tumors. Multi-color immunofluorescence across two cohorts further demonstrated conserved inverse associations between SLC46A1 and FOS expression in primary tumors and metastatic lesions. This study elucidates the molecular mechanism by which folate inhibits CRC progression through the "SLC46A1-epigenetic-transcriptional regulation" axis, providing mechanistic insights into folate deficiency-driven CRC progression and biomarkers for precision CRC intervention. This study elucidates the tumor-suppressive role of the folate transporter SLC46A1 in CRC. In normal cells, SLC46A1 facilitates folate uptake, supporting one-carbon metabolism and maintaining genomic stability. In CRC, however, SLC46A1 downregulation induces intracellular folate deficiency, triggering locus-specific DNA hypomethylation at the FOS promoter, which activates oncogenic transcription of key downstream effectors (CCND1, BCL2, PLAU), driving tumor progression. The graphical abstract illustrates the differential impact of SLC46A1 on folate metabolism and gene expression in normal versus tumor cells, highlighting its potential as a therapeutic target in CRC.

#2

A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.

Journal of inherited metabolic disease2026 Jan

Nonketotic hyperglycinemia is a severe neonatal epileptic encephalopathy caused by deficient glycine cleavage enzyme activity, for which currently no effective treatment exists. Incomplete understanding of brain biochemistry represents a major knowledge gap to develop new treatments. We examined the biochemistry in blood, liver, cortex, hippocampus, and cerebellum of a mouse model homozygous for the Gldc variant p.Ala394Val. Glycine was increased in all compartments and caused increased brain neurotoxic metabolites guanidinoacetate and methylglyoxal, and also N-acetylglycine and cystathionine. The glycine extruding transporter Slc6a20 was increased. There was reduced one-carbon folate charging with secondarily reduced methionine in the cortex, and reduced alternative one-carbon donors L-serine and formate. Serine deficiency was associated with reduced amounts of sphingosine, sphingomyelin, and ceramide species important for myelination, but not phosphatidylserines. There was a region-specific deficiency of D-serine in the cortex and hippocampus. This difference, also present in humans, was strain- and age-related, most evident in young J129X1/SvJ mice, reflecting symptomatology. There was no evidence of oxidative stress or a bioenergetic defect. The biochemistry of the nonketotic hyperglycinemia mouse model can be traced to three components: increased glycine, reduced folate one-carbon charging, and decreased L- and D-serine. These changes will need to be addressed in new therapeutic approaches.

#3

Tubule-Derived IFN-α Promotes GSDMD-Mediated Macrophage Pyroptosis to Drive Renal Inflammation and Fibrosis Through JAK2/STAT2 Activation.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)2026 Feb

Macrophages exhibit high plasticity in response to tubular epithelial cell (TEC) injury. Gasdermin D (GSDMD)-mediated pyroptosis amplifies the inflammatory and fibrogenic cascade, yet its role in chronic kidney disease (CKD) remains elusive. Herein, GSDMD is upregulated in kidney macrophages following unilateral renal ischemia-reperfusion injury (UIRI) or folic acid-induced injury, paralleling elevated pyroptosis rates. Clinically, the active fragment GSDMD-N localizes primarily to CD68⁺ macrophages, and its renal level positively correlates with fibrosis severity across diverse CKD etiologies, reinforcing its pathogenic relevance. Macrophage-specific deletion of Gsdmd ameliorates pyroptosis, inflammation, and renal fibrosis in both murine models, without affecting acute tubular damage in bilateral IRI. Mechanistically, injured TECs initiate this cascade through secreted IFN-α, which activates the IFNAR1/JAK2/STAT2 axis in macrophages​. STAT2 then forms a complex with IRF9, directly binding to the Gsdmd promoter to transcriptionally upregulate GSDMD expression. Genetic ablation of Jak2, Stat2, or Ifnar1 reduces GSDMD and GSDMD-N levels and inhibits IL-1β/IL-18 secretion. Notably, administration of an IFN-α neutralizing antibody attenuates UIRI-induced pyroptotic macrophage, inflammation, and renal fibrosis. Collectively, the findings uncover a STAT2/IRF9-dependent paracrine IFN-α feedback loop that orchestrates GSDMD-mediated pyroptosis, linking injured TECs to macrophage-driven renal inflammation and fibrosis. Targeting this axis represents a promising strategy to halt CKD progression.

#4

BiTE-secreting T cells rationally combine with PD-1 blockade and vaccine boosting to reshape antitumor immunity in ovarian cancer.

Molecular therapy : the journal of the American Society of Gene Therapy2026 Jan 07

Despite some clinical success, ovarian cancer (OC) patients rarely achieve durable benefit from current immunotherapies, suggesting a need for strategies that improve OC immune recognition. We previously reported that engineered T cells secreting folate receptor alpha (FRα)-targeted bispecific T cell engagers (FR-B T cells) elicit robust antitumor responses in OC, in part by engaging endogenous T cells. Here, we use clinical OC specimens and preclinical OC to evaluate FR-B T cells combined with PD-1 blockade. Assessing the tumor microenvironment during acute and prolonged FR-B T cell + anti-PD-1 responses revealed broad immune cell engagement/reorganization. Early CD8+ T cell-driven responses and myeloid cell influx were followed by accumulation of CXCL13-producing macrophages, activated B cells, and effector memory CD4+ T cells with durable response, hallmarks that were diminished with progressive disease. Resistant OC (characterized by FRα loss and metabolic reprogramming) emerged at disease relapse, suggesting a need to target additional vulnerabilities to extend responses. As FR-B T cells promoted epitope spreading beyond FRα, we employed a booster vaccine to enhance antitumor immunity, improving OC control. Our findings point to rationally combining FR-B T cells with PD-1 blockade in OC and an opportunity to apply personalized cancer vaccines to limit OC relapse.

#5

Folate receptor 1 activation suppresses high glucose-induced amyloidogenesis in neurons via STAT3/Nrf2 pathway-dependent mitigation of mitochondrial oxidative stress.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie2026 Mar

Diabetes is a major risk factor for diabetic encephalopathy (DE), which is closely associated with sporadic Alzheimer's disease. Folic acid (FA) receptor signaling can suppress generation of neuropathogenic amyloid-beta (Aβ) induced by high extracellular glucose, suggesting that enhanced activation of this pathway could be a therapeutic strategy against DE-associated dementia, but the precise molecular signaling mechanisms are unclear. We report that high glucose levels increased the expression of amyloid precursor protein (APP) and β-secretase (BACE1) in cultured neurons and concomitantly induced amyloidogenesis, while FA treatment suppressed high glucose-stimulated expression of APP and BACE1, Aβ release, and accumulation of mitochondrial reactive oxygen species. Expression of nuclear factor erythroid 2-related factor 2 (Nrf2) was minimal under high glucose conditions, but was significantly upregulated together with downstream antioxidant enzymes following FA co-treatment. High glucose stimulation also increased folate receptor 1 (FOLR1) mRNA expression, suggesting a compensatory protective response. While treatment with 5-methyltetrahydrofolate (5-MTHF), the activated form of folate, did not significantly alter high glucose-induced upregulation of APP and BACE1, knockdown of FOLR1 mRNA reduced high glucose-stimulated Nrf2 expression and further augmented APP and BACE1 expression under high glucose conditions. Treatment with the STAT3 inhibitor 5'15-DPP also abolished high glucose-stimulated Nrf2 expression and increased APP and BACE1 expression levels. These findings indicate that FA/FOLR1 activation suppresses high glucose-induced amyloidogenesis by mitigating mitochondrial oxidative stress via STAT3/Nrf2 pathway signaling. In conclusion, present study suggests that the FA/FOLR1/STAT3/Nrf2 pathway is an effective therapeutic target for DE.

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📚 EuropePMCmostrando 199

2026

Folate receptor 1 activation suppresses high glucose-induced amyloidogenesis in neurons via STAT3/Nrf2 pathway-dependent mitigation of mitochondrial oxidative stress.

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
2026

SLC46A1 deficiency-mediated folate restriction suppresses colorectal cancer progression through epigenetic-transcriptional reprogramming.

Cell death & disease
2026

Serum and cerebral folate are normal in Down Syndrome Regression Disorder.

Molecular autism
2026

In vitro exposure to the SARS-CoV-2 Spike protein subunit S1 leads to changes in several functional characteristics of human trophoblast cells.

Placenta
2026

A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.

Journal of inherited metabolic disease
2026

Structural characterization and lipid-modulating effects of an inulin-type fructan from Bacillus amyloliquefaciens D189: Unraveling the microbiota-gut-liver axis.

Carbohydrate polymers
2025

[Exploring the potential causes of sarcopenia in sepsis patients based on proteome sequencing].

Zhonghua wei zhong bing ji jiu yi xue
2025

Vascular dementia increases levels of methylenetetrahydrofolate reductase and cystathionine β-synthase in female patients and changes gene expression of acetylcholine and glutamate clathrin-sculpted transport vesicles.

bioRxiv : the preprint server for biology
2026

Tubule-Derived IFN-α Promotes GSDMD-Mediated Macrophage Pyroptosis to Drive Renal Inflammation and Fibrosis Through JAK2/STAT2 Activation.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
2025

An Alternative Metabolic Pathway of Glucose Oxidation Induced by Mitochondrial Complex I Inhibition: Serinogenesis and Folate Cycling.

International journal of molecular sciences
2026

A dysregulated hepcidin-iron axis impairs antiviral immunity and induces lethal liver pathology in neonates.

Immunity
2026

Manganese activates the CBASS immunity to protect bacteria from phage infection.

mBio
2025

Real-world insights into the prevalence and prognostic significance of trophoblast cell-surface antigen 2 and folate receptor alpha in uterine carcinosarcoma.

BMC cancer
2025

Breast Cancer Progression and Its Theranostic Management via Folate-Directed Targeting of Glycoprotein Receptor.

Medical sciences (Basel, Switzerland)
2025

Comparative Analysis of Treatment With Folate Forms in Clinical Practice.

Nutrition reviews
2026

Exploring novel therapeutic targets in vulvar squamous cell carcinoma.

Gynecologic oncology
2025

Maternal Folate Receptor Alpha Autoantibodies and Increased Fetal Nuchal Translucency as Potential Early Markers of Autism Spectrum Disorder.

Brain and behavior
2026

Protective effects of pyrroloquinoline quinone in CNS disorders.

The Journal of nutritional biochemistry
2026

Heterogeneity and Scoring Reproducibility of Folate Receptor 1 Immunohistochemistry in High-grade Serous Carcinoma.

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
2026

Vitamin A acts as a potent suppressor of selenoprotein P with potential relevance for multivitamin supplementation.

The Journal of nutritional biochemistry
2026

BiTE-secreting T cells rationally combine with PD-1 blockade and vaccine boosting to reshape antitumor immunity in ovarian cancer.

Molecular therapy : the journal of the American Society of Gene Therapy
2025

Folate disorder in the atdfb mutant triggers a compensatory nitrogen starvation response by altering nitrate transport and assimilation.

Biochemical and biophysical research communications
2025

Transgenerational Effects and Heritability of Folate Receptor Alpha Autoantibodies in Autism Spectrum Disorder.

International journal of molecular sciences
2025

Preclinical Evaluation of Folate Receptor-α Chimeric Antigen Receptor T Cells Exhibits Highly Efficient Antitumor Activity against Osteosarcoma.

Cancer research communications
2025

A novel treatment for diabetic nephropathy: Folate receptor-targeted delivery of TLR4 siRNA via functionalized PLGA nanoparticles in streptozotocin-induced diabetic murine models.

Nanomedicine : nanotechnology, biology, and medicine
2025

Exploring neuropsychiatric manifestations of vitamin B complex deficiencies.

Frontiers in psychiatry
2025

Branched-chain amino acids contribute to diabetic kidney disease progression via PKM2-mediated podocyte metabolic reprogramming and apoptosis.

Nature communications
2025

Treatable and preventable causes of inborn errors of metabolism: Cohort of neurotransmitter disorders in children from India.

Brain & development
2025

Evaluation of thymidine kinase 1 and folate receptor alpha as potential biomarkers in prostate cancer.

Scientific reports
2025

Radiocleavable rare-earth nanoactivators targeting over-expressed folate receptors induce mitochondrial dysfunction and remodel immune suppressive microenvironment in pancreatic cancer.

Journal of nanobiotechnology
2025

ndufs2-/- zebrafish have impaired survival, neuromuscular activity, morphology, and one-carbon metabolism treatable with folic acid.

bioRxiv : the preprint server for biology
2025

Rationale Design of a Zn(II)-Coordinated, Cell Penetrating, and Functionalized Tetrapeptide Self-Assembly for Delivery of Chemotherapeutic Drugs to Folic Acid Receptor-Expressing Cancer Cells.

ACS applied bio materials
2025

Optimization and Validation of a Folate Ligand-Targeted qPCR Method for Detection of Folate Receptor-Positive Circulating Tumor Cells in Gastric Cancer.

Asian Pacific journal of cancer prevention : APJCP
2025

Neuroprotective role of pyrroloquinoline quinone in folate deficiency-induced blood-brain barrier disruption.

Fluids and barriers of the CNS
2026

Antibody-drug Conjugate Biomarker Expression in Gestational Trophoblastic Disease: Folate Receptor Alpha, Nectin-4, Trop-2, and Tissue Factor.

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
2025

A novel truncated mutation in folate receptor α (FRα) affecting its glycosylation and affinity for folate in a consanguineous family with progressive encephalopathy: follow up and treatment improvement.

Molecular biology reports
2025

Antitumor Effect of Farletuzumab Ecteribulin in Molecular Subtypes of Endometrial Cancer Patient-Derived Xenograft Models.

Molecular cancer therapeutics
2025

Mirvetuximab soravtansine for the treatment of epithelial ovarian, fallopian tube, or primary peritoneal cancer.

Future oncology (London, England)
2025

Folic acid supplementation on congenital heart disease and its dual character.

Current research in pharmacology and drug discovery
2025

Serum metabolomics reveals systemic metabolic alterations of Graves' disease before and after antithyroid drug treatment.

Endocrine connections
2025

Nhe1 is required for directional sensing in vegetative Dictyostelium cell migration.

Cell adhesion & migration
2025

Novel susceptibility gene SLC23A2 functions via PI3K-AKT-mTOR pathway in etiology of non-syndromic cleft palate.

Journal of human genetics
2025

Choline in Pediatric Nutrition: Assessing Formula, Fortifiers and Supplements Across Age Groups and Clinical Indications.

Nutrients
2025

The Role of Folate Receptor α Autoantibodies in Folate Deficiency, Disease Severity, and Treatment Response in Adolescents with Major Depressive Disorder.

The Journal of nutrition
2025

PCFT-Independent Cellular Uptake of Cyclic Cell-Penetrating Peptide-Conjugated Folic Acid.

Chembiochem : a European journal of chemical biology
2025

FRα expression in advanced endometrial carcinoma: Clinicopathological, molecular, and prognosis correlates.

Gynecologic oncology
2025

Silencing GGH induces autophagy by increasing folate stress and production of NADH.

Journal of molecular cell biology
2025

Genomic characterization of Leishmania (V.) braziliensis associated with antimony therapeutic failure and variable in vitro tolerance to amphotericin B.

Scientific reports
2025

A Clinical and Genetic Evaluation of Cases with Folate Receptor α Gene Mutation: A Case Series from Türkiye.

Diagnostics (Basel, Switzerland)
2025

Folic acid-conjugated amphiphilic copolymers for the enhanced delivery of donepezil: synthesis, characterization and blood-brain barrier permeability in a co-culture model.

Journal of biomaterials science. Polymer edition
2025

Patient-reported outcomes from the MIRASOL trial evaluating mirvetuximab soravtansine versus chemotherapy in patients with folate receptor α-positive, platinum-resistant ovarian cancer: a randomised, open-label, phase 3 trial.

The Lancet. Oncology
2025

Analysis of the Association Between the SLC19A1 Genetic Variant (rs1051266) and Autism Spectrum Disorders, Cerebral Folate Deficiency, and Clinical and Laboratory Parameters.

Journal of molecular neuroscience : MN
2025

Sex-specific modulation of FOLR1 and its cycle enzyme genes in Alzheimer's disease brain regions.

Metabolic brain disease
2025

FOLR1 as a therapeutic target in platinum-resistant ovarian carcinoma: unique expression patterns across ovarian carcinoma histotypes and molecular subtypes of low-grade serous carcinoma.

Journal of gynecologic oncology
2025

A review of mirvetuximab soravtansine-gynx in folate receptor alpha-expressing platinum-resistant ovarian cancer.

American journal of health-system pharmacy : AJHP : official journal of the American Society of Health-System Pharmacists
2025

Mirvetuximab soravtansine: current and future applications.

Journal of hematology & oncology
2025

SLC19A1 Gene Polymorphism; Risk Factor for Preeclampsia.

Journal of the College of Physicians and Surgeons--Pakistan : JCPSP
2025

Mirvetuximab Soravtansine Induces Potent Cytotoxicity and Bystander Effect in Cisplatin-Resistant Germ Cell Tumor Cells.

Cells
2025

Mechanistic insights into mutation in the proton-coupled folate transporter (SLC46A1) causing hereditary folate malabsorption.

The Journal of biological chemistry
2026

FOLR1 Regulates the Malignant Progression of Glioblastoma through the SRC/ERK1/2 Axis.

Combinatorial chemistry & high throughput screening
2025

Association of Reduced Folate Carrier G80A Polymorphism With Lung Cancer Susceptibility in a Hypertensive Population: A Nested Case-Control Study.

The Journal of nutrition
2024

Epigenetics of Homocystinuria, Hydrogen Sulfide, and Circadian Clock Ablation in Cardiovascular-Renal Disease.

Current issues in molecular biology
2025

Intraoperative Molecular Imaging With Pafolacianine: Histologic Characteristics of Identified Nodules.

Clinical lung cancer
2025

Hierarchical Targeting Nanodrug with Holistic DNA Protection for Effective Treatment of Acute Kidney Injury.

Advanced science (Weinheim, Baden-Wurttemberg, Germany)
2025

Analysis of real world FRα testing in ovarian, fallopian tube, and primary peritoneal cancers.

Gynecologic oncology
2025

The efficacy and safety of mirvetuximab soravtansine in FRα-positive, third-line and later, recurrent platinum-sensitive ovarian cancer: the single-arm phase II PICCOLO trial.

Annals of oncology : official journal of the European Society for Medical Oncology
2024

Folate Receptor Alpha-A Secret Weapon in Ovarian Cancer Treatment?

International journal of molecular sciences
2024

Effect of Genotype on the Response to Diet in Cardiovascular Disease-A Scoping Review.

Healthcare (Basel, Switzerland)
2024

Enhancing mitochondrial one-carbon metabolism is neuroprotective in Alzheimer's disease models.

Cell death & disease
2025

Thiamine-Responsive Megaloblastic Anemia Syndrome Mimicking Myelodysplastic Neoplasm.

Acta haematologica
2024

Lactobacillus Eats Amyloid Plaque and Post-Biotically Attenuates Senescence Due to Repeat Expansion Disorder and Alzheimer's Disease.

Antioxidants (Basel, Switzerland)
2024

Development of folate receptor targeting chimeras for cancer selective degradation of extracellular proteins.

Nature communications
2024

Characterizing the genomic landscape through the lens of FOLR1 status in low and high grade serous ovarian carcinoma.

Gynecologic oncology
2024

Panax notoginseng saponins and acetylsalicylic acid co-delivered liposomes for targeted treatment of ischemic stroke.

International journal of pharmaceutics
2025

Exposure-response relationships of mirvetuximab soravtansine in patients with folate receptor-α-positive ovarian cancer: Justification of therapeutic dose regimen.

British journal of clinical pharmacology
2024

Calorie restriction exacerbates folic acid-induced kidney fibrosis by altering mitochondria metabolism.

The Journal of nutritional biochemistry
2024

A Homozygous Variant in NAA60 Is Associated with Primary Familial Brain Calcification.

Movement disorders : official journal of the Movement Disorder Society
2024

Short-term feed restriction induces inflammation and an antioxidant response via cystathionine-β-synthase and glutathione peroxidases in ruminal epithelium from Angus steers.

Journal of animal science
2024

PARP-1, EpCAM, and FRα as potential targets for intraoperative detection and delineation of endometriosis: a quantitative tissue expression analysis.

Reproductive biology and endocrinology : RB&E
2024

Folic Acid-Functionalized β-Cyclodextrin for Delivery of Organelle-Targeted Peptide Chemotherapeutics in Cancer.

Molecular pharmaceutics
2024

Role of gut/liver metabolites and gut microbiota in liver fibrosis caused by cholestasis.

International immunopharmacology
2024

Congenital Heart Disease and Genetic Changes in Folate/Methionine Cycles.

Genes
2024

SGLT2 inhibition leads to a restoration of hepatic and circulating metabolites involved in the folate cycle and pyrimidine biosynthesis.

American journal of physiology. Gastrointestinal and liver physiology
2025

Folate Receptor Immunohistochemical Staining and Gynecologic Tumors: Initial Experience With 216 Cases.

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
2024

Dolutegravir- Versus Efavirenz-Based Treatment in Pregnancy: Impact on Red Blood Cell Folate Concentrations in Pregnant Women and Their Infants.

The Journal of infectious diseases
2024

Mirvetuximab soravtansine in folate receptor alpha (FRα)-high platinum-resistant ovarian cancer: final overall survival and post hoc sequence of therapy subgroup results from the SORAYA trial.

International journal of gynecological cancer : official journal of the International Gynecological Cancer Society
2024

Combined ROS Sensitive Folate Receptor Targeted Micellar Formulations of Curcumin Effective Against Rheumatoid Arthritis in Rat Model.

International journal of nanomedicine
2024

Effect of probiotic administration during pregnancy on the functional diversity of the gut microbiota in healthy pregnant women.

Microbiology spectrum
2024

Folic Acid-Conjugated Brush Polymers Show Enhanced Blood-Brain Barrier Crossing in Static and Dynamic In Vitro Models Toward Brain Cancer Targeting Therapy.

ACS biomaterials science & engineering
2024

CD163-Mediated Small-Vessel Injury in Alzheimer's Disease: An Exploration from Neuroimaging to Transcriptomics.

International journal of molecular sciences
2024

Relationship between Changes of Serum Vascular Endothelial Growth Factor and Folate Receptor-α Levels and Clinical Efficacy of Toripalimab in Patients with Bladder Cancer.

Archivos espanoles de urologia
2024

Remimazolam attenuates inflammation and kidney fibrosis following folic acid injury.

European journal of pharmacology
2024

WNT-dependent interaction between inflammatory fibroblasts and FOLR2+ macrophages promotes fibrosis in chronic kidney disease.

Nature communications
2024

GSDMD and GSDME synergy in the transition of acute kidney injury to chronic kidney disease.

Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
2024

Expression of the cobalamin transporters cubam and MRP1 in the canine ileum-Upregulation in chronic inflammatory enteropathy.

PloS one
2023

Insight into the mechanism of gallstone disease by proteomic and metaproteomic characterization of human bile.

Frontiers in microbiology
2024

Maternal folic acid and vitamin B12 supplementation during medium to late gestation promotes fetal development via improving placental antioxidant capacity, angiogenesis and amino acid transport.

Journal of the science of food and agriculture
2024

Sensitivity and specificity of folate receptor α-positive circulating tumour cells in gastric cancer.

Postgraduate medical journal
2023

Lineage specific extracellular vesicle-associated protein biomarkers for the early detection of high grade serous ovarian cancer.

Scientific reports
2023

Mutational analysis of FOLR1 and FOLR2 genes in children with Myelomeningocele.

Acta biochimica Polonica
2023

Metabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome.

Clinical epigenetics
2023

A sub-10-nm, folic acid-conjugated gold nanoparticle as self-therapeutic treatment of tubulointerstitial fibrosis.

Proceedings of the National Academy of Sciences of the United States of America
2023

Alginate biopolymeric structures: Versatile carriers for bioactive compounds in functional foods and nutraceutical formulations: A review.

International journal of biological macromolecules
2024

Effects of folate deficiency and sex on carcinogenesis in a mouse model of oral cancer.

Oral diseases
2023

Anemia, Iron Deficiency, and Iron Regulators in Pancreatic Ductal Adenocarcinoma Patients: A Comprehensive Analysis.

Current oncology (Toronto, Ont.)
2023

FRET-based probe for ratiometric detection and imaging of folic acid in real-time.

Analytical biochemistry
2023

Lysinuric protein intolerance presenting as pancytopenia and splenomegaly mimicking acute leukaemia: a case report.

BMC pediatrics
2023

TJ-17 (Goreisan) mitigates renal fibrosis in a mouse model of folic acid-induced chronic kidney disease.

Journal of pharmacological sciences
2023

Maternal metabolism influences neural tube closure.

Trends in endocrinology and metabolism: TEM
2023

Hypomyelination caused by a novel homozygous pathogenic variant in FOLR1: complete clinical and radiological recovery with oral folinic acid therapy and review of the literature.

Orphanet journal of rare diseases
2023

Folate receptor targeted NIR cleavable liposomal delivery system augment penetration and therapeutic efficacy in breast cancer.

Biochimica et biophysica acta. General subjects
2023

Serine metabolism during differentiation of human iPSC-derived astrocytes.

The FEBS journal
2023

The Influence of Alcohol Consumption on Intestinal Nutrient Absorption: A Comprehensive Review.

Nutrients
2023

Enhancer of zeste homolog 2 promotes renal fibrosis after acute kidney injury by inducing epithelial-mesenchymal transition and activation of M2 macrophage polarization.

Cell death & disease
2023

Dietary Folate Deficiency Promotes Lactate Metabolic Disorders to Sensitize Lung Cancer Metastasis through MTOR-Signaling-Mediated Druggable Oncotargets.

Nutrients
2023

Brain Uptake of Folate Forms in the Presence of Folate Receptor Alpha Antibodies in Young Rats: Folate and Antibody Distribution.

Nutrients
2023

Reanalysis of exome sequencing data reveals a treatable neurometabolic origin in two previously undiagnosed siblings with neurodevelopmental disorder.

Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology
2023

Impaired Function of Solute Carrier Family 19 Leads to Low Folate Levels and Lipid Droplet Accumulation in Hepatocytes.

Biomedicines
2023

Newcastle Disease Virus Manipulates Mitochondrial MTHFD2-Mediated Nucleotide Metabolism for Virus Replication.

Journal of virology
2023

The role of maternal choline, folate and one-carbon metabolism in mediating the impact of prenatal alcohol exposure on placental and fetal development.

The Journal of physiology
2022

Transcriptomic profiling of hepatic tissues for drug metabolism genes in nonalcoholic fatty liver disease: A study of human and animals.

Frontiers in endocrinology
2023

A Paternal Methylation Error in the Congenital Hydrocephalic Texas (H-Tx) Rat Is Partially Rescued with Natural Folate Supplements.

International journal of molecular sciences
2022

Cerebral Folate Metabolism in Post-Mortem Alzheimer's Disease Tissues: A Small Cohort Study.

International journal of molecular sciences
2023

Formononetin ameliorates ferroptosis-associated fibrosis in renal tubular epithelial cells and in mice with chronic kidney disease by suppressing the Smad3/ATF3/SLC7A11 signaling.

Life sciences
2022

High Expression of Folate Receptor Alpha (FOLR1) is Associated With Aggressive Tumor Behavior, Poor Response to Chemoradiotherapy, and Worse Survival in Rectal Cancer.

Technology in cancer research & treatment
2022

Novel localization of folate transport systems in the murine central nervous system.

Fluids and barriers of the CNS
2023

Decline of stress resilience in aging rats: Focus on choroid plexus-cerebrospinal fluid-hippocampus.

The world journal of biological psychiatry : the official journal of the World Federation of Societies of Biological Psychiatry
2023

Folate receptor alpha in ovarian cancer tissue and patient serum is associated with disease burden and treatment outcomes.

British journal of cancer
2023

Elevated expression of receptors for EGF, PDGF, transferrin and folate within murine and human lupus nephritis kidneys.

Clinical immunology (Orlando, Fla.)
2022

Shotgun Metagenomics Study Suggests Alteration in Sulfur Metabolism and Oxidative Stress in Children with Autism and Improvement after Microbiota Transfer Therapy.

International journal of molecular sciences
2022

Genetic Aspects of Micronutrients Important for Inflammatory Bowel Disease.

Life (Basel, Switzerland)
2022

Recognition of cyclic dinucleotides and folates by human SLC19A1.

Nature
2022

Ultrasmall Folate Receptor Alpha Targeted Enzymatically Cleavable Silica Nanoparticle Drug Conjugates Augment Penetration and Therapeutic Efficacy in Models of Cancer.

ACS nano
2022

CBFA2T3-GLIS2 model of pediatric acute megakaryoblastic leukemia identifies FOLR1 as a CAR T cell target.

The Journal of clinical investigation
2022

Targeted Mitochondrial Epigenetics: A New Direction in Alzheimer's Disease Treatment.

International journal of molecular sciences
2022

Evaluation of the antimicrobial function of Ginkgo biloba exocarp extract against clinical bacteria and its effect on Staphylococcus haemolyticus by disrupting biofilms.

Journal of ethnopharmacology
2023

ZOOMICS : comparative metabolomics of red blood cells from dogs, cows, horses and donkeys during refrigerated storage for up to 42 days.

Blood transfusion = Trasfusione del sangue
2022

Cerebral Folate Deficiency Syndrome: Early Diagnosis, Intervention and Treatment Strategies.

Nutrients
2022

Gain-of-function, focal segmental glomerulosclerosis Trpc6 mutation minimally affects susceptibility to renal injury in several mouse models.

PloS one
2022

Boron Nitride Nanoparticles Loaded with a Boron-Based Hybrid as a Promising Drug Carrier System for Alzheimer's Disease Treatment.

International journal of molecular sciences
2022

Ischemic Stroke and Dietary Vitamin B12 Deficiency in Old-Aged Females: Impaired Motor Function, Increased Ischemic Damage Size, and Changed Metabolite Profiles in Brain and Cecum Tissue.

Nutrients
2022

Integrated proteomics and metabolomics analysis reveals hubs protein and network alterations in myasthenia gravis.

Aging
2022

Absorption and Tissue Distribution of Folate Forms in Rats: Indications for Specific Folate Form Supplementation during Pregnancy.

Nutrients
2022

Mitochondrial FAD shortage in SLC25A32 deficiency affects folate-mediated one-carbon metabolism.

Cellular and molecular life sciences : CMLS
2023

Pralatrexate for Peripheral T-Cell Lymphoma (PTCL): Chance Only Supports The Prepared Mind.

Anti-cancer agents in medicinal chemistry
2022

A female case of 5,10-methenyltetrahydrofolate synthetase deficiency with novel neuro-imaging abnormalities.

Brain & development
2022

Global DNA hypomethylation of colorectal tumours detected in tissue and liquid biopsies may be related to decreased methyl-donor content.

BMC cancer
2022

Vitamin B12 as a cholinergic system modulator and blood brain barrier integrity restorer in Alzheimer's disease.

European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences
2022

Folate Receptor Expression by Human Monocyte-Derived Macrophage Subtypes and Effects of Corticosteroids.

Cartilage
2022

Mechanosensitive Piezo1 channels mediate renal fibrosis.

JCI insight
2022

Folic Acid-Adorned Curcumin-Loaded Iron Oxide Nanoparticles for Cervical Cancer.

ACS applied bio materials
2022

Folate Receptor Beta for Macrophage Imaging in Rheumatoid Arthritis.

Frontiers in immunology
2022

Genetic inactivation of Semaphorin 3C protects mice from acute kidney injury.

Kidney international
2022

A novel role of BK potassium channel activity in preventing the development of kidney fibrosis.

Kidney international
2022

Detection of folate receptor-positive circulating tumor cells as a biomarker for diagnosis, prognostication, and therapeutic monitoring in breast cancer.

Journal of clinical laboratory analysis
2021

Designing of a pH-activatable carbon dots as a luminescent nanoprobe for recognizing folate receptor-positive cancer cells.

Nanotechnology
2021

The Cerebrospinal Fluid Concentration of Methyltetrahydrofolate and Serum Folate in Children with Developmental Delay, Regression, and/or Refractory Epilepsy.

Neurology India
2021

Effectiveness of Some Vitamins in the Prevention of Cardiovascular Disease: A Narrative Review.

Frontiers in physiology
2021

Molecular Insight into the Effect of a Single-Nucleotide Polymorphic Variation on the Structure and Dynamics of Methionine Synthase Reductase and Its Association with Neural Tube Defects.

ACS omega
2021

A Novel Treatment for Glomerular Disease: Targeting the Activated Macrophage Folate Receptor with a Trojan Horse Therapy in Rats.

Cells
2021

Folic Acid and Autism: A Systematic Review of the Current State of Knowledge.

Cells
2021

A single genetic locus controls both expression of DPEP1/CHMP1A and kidney disease development via ferroptosis.

Nature communications
2022

The Plasmodium falciparum ABC transporter ABCI3 confers parasite strain-dependent pleiotropic antimalarial drug resistance.

Cell chemical biology
2021

The Concept of Folic Acid in Health and Disease.

Molecules (Basel, Switzerland)
2021

Arabidopsis non-host resistance PSS30 gene enhances broad-spectrum disease resistance in the soybean cultivar Williams 82.

The Plant journal : for cell and molecular biology
2021

Ischemia-Reperfusion Injury Reduces Kidney Folate Transporter Expression and Plasma Folate Levels.

Frontiers in immunology
2021

Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention.

Frontiers in neuroscience
2021

Immunotherapy using IgE or CAR T cells for cancers expressing the tumor antigen SLC3A2.

Journal for immunotherapy of cancer
2021

A Role for Folate in Microbiome-Linked Control of Autoimmunity.

Journal of immunology research
2021

Oral Administration of Ginger-Derived Lipid Nanoparticles and Dmt1 siRNA Potentiates the Effect of Dietary Iron Restriction and Mitigates Pre-Existing Iron Overload in Hamp KO Mice.

Nutrients
2021

Folic acid alleviates the blood brain barrier permeability and oxidative stress and prevents cognitive decline in sepsis-surviving rats.

Microvascular research
2021

The feasibility of folate receptor alpha- and HER2-targeted intraoperative fluorescence-guided cytoreductive surgery in women with epithelial ovarian cancer: A systematic review.

Gynecologic oncology
2021

Structural basis of antifolate recognition and transport by PCFT.

Nature
2021

Cerebral folate transporter deficiency syndrome in three siblings: Why genetic testing for developmental and epileptic encephalopathies should be performed early and include the FOLR1 gene.

American journal of medical genetics. Part A
2023

Cerebral folate transporter deficiency: a potentially treatable neurometabolic disorder.

Acta neurologica Belgica
2021

Preparation of FA-targeted magnetic nanocomposites co-loading TFPI-2 plasmid and cis-platinum and its targeted therapy effects on nasopharyngeal carcinoma.

International journal of medical sciences
2021

Folate-targeted verrucarin A reduces the number of activated macrophages in a mouse model of acute peritonitis.

Bioorganic & medicinal chemistry letters
2021

Association of maternal folate use and reduced folate carrier gene polymorphisms with the risk of congenital heart disease in offspring.

European journal of pediatrics
2021

Genetic polymorphism in ATIC is associated with effectiveness and toxicity of pemetrexed in non-small-cell lung cancer.

Thorax
2021

Identification of fibroblast activation-related genes in two acute kidney injury models.

PeerJ
2021

In Vitro and In Vivo Efficacy of a Novel Glucose-Methotrexate Conjugate in Targeted Cancer Treatment.

International journal of molecular sciences
2020

Immune Privilege: The Microbiome and Uveitis.

Frontiers in immunology
2021

Efficacy and tolerability of folate-aminopterin therapy in a rat focal model of multiple sclerosis.

Journal of neuroinflammation
2021

Fourth-generation chimeric antigen receptor T cells targeting folate receptor alpha antigen expressed on breast cancer cells for adoptive T cell therapy.

Breast cancer research and treatment
2021

Co-expression patterns of chimeric antigen receptor (CAR)-T cell target antigens in primary and recurrent ovarian cancer.

Gynecologic oncology
2021

Folate Receptor Alpha Is Preferentially Expressed in the Carcinoma Component of Endometrial Carcinosarcomas: A Potential Target for Adjuvant Therapy.

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
2020

Altered metabolism of mothers of young children with Autism Spectrum Disorder: a case control study.

BMC pediatrics
2021

Perspectives of Methotrexate-Based Radioagents for Application in Nuclear Medicine.

Molecular pharmaceutics
2020

First case report of cerebral folate deficiency caused by a novel mutation of FOLR1 gene in a Chinese patient.

BMC medical genetics
2020

[Remethylation disorders: about two cases].

Annales de biologie clinique
2021

Development of technetium-99m labeled ultrafine gold nanobioconjugates for targeted imaging of folate receptor positive cancers.

Nuclear medicine and biology
2021

PNN and KCNQ1OT1 Can Predict the Efficacy of Adjuvant Fluoropyrimidine-Based Chemotherapy in Colorectal Cancer Patients.

Oncology research
2021

Androgenetic/Biparental Mosaic/Chimeric Conceptions With a Molar Component: A Diagnostic and Clinical Challenge.

International journal of gynecological pathology : official journal of the International Society of Gynecological Pathologists
2020

Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients.

Nature communications
2021

Intraoperative Molecular Imaging Utilizing a Folate Receptor-Targeted Near-Infrared Probe Can Identify Macroscopic Gastric Adenocarcinomas.

Molecular imaging and biology
2020

In Vitro and In Vivo Evaluation of Novel DTX-Loaded Multifunctional Heparin-Based Polymeric Micelles Targeting Folate Receptors and Endosomes.

Recent patents on anti-cancer drug discovery
2020

Lessons Learned from Inherited Metabolic Disorders of Sulfur-Containing Amino Acids Metabolism.

The Journal of nutrition
2021

A phase II study of Mirvetuximab Soravtansine in triple-negative breast cancer.

Investigational new drugs
2020

Onco-fetal Reprogramming of Endothelial Cells Drives Immunosuppressive Macrophages in Hepatocellular Carcinoma.

Cell

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Doenças relacionadas

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Referências e fontes

Bases de dados externas citadas neste artigo

Publicações científicas

Artigos indexados no PubMed ligados a esta doença no grafo RarasNet — título, periódico e PMID direto da fonte, sem intermediação de IA.

  1. SLC46A1 deficiency-mediated folate restriction suppresses colorectal cancer progression through epigenetic-transcriptional reprogramming.
    Cell death & disease· 2026· PMID 41620398mais citado
  2. A Nonketotic Hyperglycinemia Mouse Shows Wide-Ranging Biochemical Consequences of Elevated Glycine, Reduced Folate One-Carbon Charging, and Serine Deficiency.
    Journal of inherited metabolic disease· 2026· PMID 41603187mais citado
  3. Tubule-Derived IFN-α Promotes GSDMD-Mediated Macrophage Pyroptosis to Drive Renal Inflammation and Fibrosis Through JAK2/STAT2 Activation.
    Advanced science (Weinheim, Baden-Wurttemberg, Germany)· 2026· PMID 41387110mais citado
  4. BiTE-secreting T cells rationally combine with PD-1 blockade and vaccine boosting to reshape antitumor immunity in ovarian cancer.
    Molecular therapy : the journal of the American Society of Gene Therapy· 2026· PMID 41029902mais citado
  5. Folate receptor 1 activation suppresses high glucose-induced amyloidogenesis in neurons via STAT3/Nrf2 pathway-dependent mitigation of mitochondrial oxidative stress.
    Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie· 2026· PMID 41633894mais citado
  6. Mast cell mediators in hereditary angioedema.
    Orphanet J Rare Dis· 2026· PMID 41832580recente
  7. Prenatal Molecular Diagnosis of COL2A1-Associated Stickler Syndrome: Genotype-Phenotype Correlation in a Resource-Limited Healthcare Setting.
    Int J Mol Sci· 2026· PMID 41828453recente
  8. Platelet gene signatures detecting pulmonary artery stenosis in patients with pulmonary hypertension.
    Orphanet J Rare Dis· 2026· PMID 41827036recente
  9. The global impact of imiglucerase therapy in children with Gaucher disease types 1 and 3: a real-world analysis from the International Collaborative Gaucher Group Gaucher Registry.
    Orphanet J Rare Dis· 2026· PMID 41821052recente
  10. Monogenic lupus with SLC7A7 mutations: a retrospective study from a Chinese center.
    Orphanet J Rare Dis· 2026· PMID 41821046recente

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:285657(Orphanet)
  2. MONDO:0017313(MONDO)
  3. GARD:21131(GARD (NIH))
  4. Variantes catalogadas(ClinVar)
  5. Busca completa no PubMed(PubMed)
  6. Q55786977(Wikidata)

Dados compilados pelo RarasNet a partir de fontes abertas (Orphanet, OMIM, MONDO, PubMed/EuropePMC, ClinicalTrials.gov, DATASUS, PCDT/MS). Este conteúdo é informativo e não substitui avaliação médica.

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Doença do metabolismo do folato
Compêndio · Raras BR

Doença do metabolismo do folato

ORPHA:285657 · MONDO:0017313
CID-11
MedGen
UMLS
C5681010
Wikidata
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