Doença metabólica hereditária que afeta a absorção intestinal da cobalamina (vitamina B12), o transporte no sangue, a captação pelas células periféricas ou o metabolismo celular.
Introdução
O que você precisa saber de cara
Doença metabólica hereditária que afeta a absorção intestinal da cobalamina (vitamina B12), o transporte no sangue, a captação pelas células periféricas ou o metabolismo celular.
Encontrou um erro ou informação desatualizada? Sugira uma correção →
Entender a doença
Do básico ao detalhe, leia no seu ritmo
Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 109 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 262 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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
16 genes identificados com associação a esta condição.
Thiol-specific peroxidase that catalyzes the reduction of hydrogen peroxide and organic hydroperoxides to water and alcohols, respectively. Plays a role in cell protection against oxidative stress by detoxifying peroxides and as sensor of hydrogen peroxide-mediated signaling events. Might participate in the signaling cascades of growth factors and tumor necrosis factor-alpha by regulating the intracellular concentrations of H(2)O(2) (PubMed:9497357). Reduces an intramolecular disulfide bond in G
CytoplasmMelanosome
Primary vitamin B12-binding and transport protein. Delivers cobalamin to cells
Secreted
Transcobalamin II deficiency
An autosomal recessive disorder manifesting in early infancy and characterized by failure to thrive, megaloblastic anemia, pancytopenia, and agammaglobulinemia. Additional features include methylmalonic aciduria, recurrent infections, vomiting and diarrhea. TCN2D may be accompanied by neurological complications, including psychomotor and mental developmental delay, if untreated.
Receptor for transcobalamin saturated with cobalamin (TCbl) (PubMed:18779389). Plays an important role in cobalamin uptake (PubMed:18779389, PubMed:20524213). Plasma membrane protein that is expressed on follicular dendritic cells (FDC) and mediates interaction with germinal center B cells (PubMed:10727470). Functions as costimulator to promote B cell responses to antigenic stimuli; promotes B cell differentiation and proliferation (PubMed:10727470, PubMed:11418631). Germinal center-B (GC-B) cel
Cell membrane
Methylmalonic aciduria, transient, due to transcobalamin receptor defect
An autosomal recessive metabolic condition characterized by moderate methymalonicaciduria, and normal plasma vitamin B12 levels. Serum homocysteine may be increased in some affected individuals. Most cases are clinically asymptomatic.
Endocytic receptor which plays a role in lipoprotein, vitamin and iron metabolism by facilitating their uptake (PubMed:10371504, PubMed:11606717, PubMed:11717447, PubMed:14576052, PubMed:9572993). Acts together with LRP2 to mediate endocytosis of high-density lipoproteins, GC, hemoglobin, ALB, TF and SCGB1A1. Acts together with AMN to mediate endocytosis of the CBLIF-cobalamin complex (PubMed:14576052, PubMed:9572993). Binds to ALB, MB, Kappa and lambda-light chains, TF, hemoglobin, GC, SCGB1A1,
Apical cell membraneCell membraneMembrane, coated pitEndosomeLysosome membrane
Imerslund-Grasbeck syndrome 1
A form of Imerslund-Grasbeck syndrome, a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in infancy or early childhood. Clinical manifestations include failure to thrive, infections and neurological damage. Mild proteinuria, with no signs of kidney disease, is present in about half of the patients.
Transcription factor, which has both transcriptional activation and repression activities (PubMed:31905202). Also modulates chromatin accessibility (PubMed:38361031). In complex with HCFC1 and ZNF143, regulates the expression of several genes, including AP2S1, ESCO2, OPHN1, RBL1, UBXN8 and ZNF32 (PubMed:26416877). May regulate the expression of genes that encode both cytoplasmic and mitochondrial ribosomal proteins (By similarity). Required for normal mitochondrial development and function. Regu
NucleusCytoplasm
Methylmalonic aciduria and homocystinuria type cblL
An autosomal recessive disorder of cobalamin metabolism clinically characterized by early-onset seizures, and profound global developmental delay with severe intellectual disability. Metabolic features are mild methylmalonic aciduria, low-normal plasma methionine, and high-normal plasma homocysteine.
Promotes absorption of the essential vitamin cobalamin (Cbl) in the ileum. After interaction with CUBN, the CBLIF-cobalamin complex is internalized via receptor-mediated endocytosis
Secreted
Hereditary intrinsic factor deficiency
Autosomal recessive disorder characterized by megaloblastic anemia.
Membrane-bound component of the endocytic receptor formed by AMN and CUBN (PubMed:14576052, PubMed:29402915, PubMed:30523278). Required for normal CUBN glycosylation and trafficking to the cell surface (PubMed:14576052, PubMed:29402915). The complex formed by AMN and CUBN is required for efficient absorption of vitamin B12 (PubMed:12590260, PubMed:14576052, PubMed:26040326). Required for normal CUBN-mediated protein transport in the kidney (Probable)
Apical cell membraneCell membraneEndosome membraneMembrane, coated pitSecreted
Imerslund-Grasbeck syndrome 2
A form of Imerslund-Grasbeck syndrome, a rare autosomal recessive disorder characterized by vitamin B12 deficiency commonly resulting in megaloblastic anemia, which is responsive to parenteral vitamin B12 therapy and appears in infancy or early childhood. Clinical manifestations include failure to thrive, infections and neurological damage. Mild proteinuria, with no signs of kidney disease, is present in about half of the patients.
Converts cob(I)alamin to adenosylcobalamin (adenosylcob(III)alamin), a coenzyme for methylmalonyl-CoA mutase, therefore participates in the final step of the vitamin B12 conversion (PubMed:12514191). Generates adenosylcobalamin (AdoCbl) and directly delivers the cofactor to MUT in a transfer that is stimulated by ATP-binding to MMAB and gated by MMAA (Probable)
Mitochondrion
Methylmalonic aciduria, cblB type
An autosomal recessive disorder of methylmalonate and cobalamin metabolism due to defective synthesis of adenosylcobalamin.
Lysosomal membrane protein that transports cobalamin (Vitamin B12) from the lysosomal lumen to the cytosol in an ATP-dependent manner (PubMed:22922874, PubMed:28572511, PubMed:31467407, PubMed:33845046). Targeted by LMBRD1 lysosomal chaperone from the endoplasmic reticulum to the lysosomal membrane (PubMed:27456980). Then forms a complex with lysosomal chaperone LMBRD1 and cytosolic MMACHC to transport cobalamin across the lysosomal membrane (PubMed:25535791)
Endoplasmic reticulum membraneLysosome membrane
Methylmalonic aciduria and homocystinuria type cblJ
A disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include feeding difficulties, poor growth, hypotonia, lethargy, anemia, and developmental delay.
Key enzyme in methionine and folate homeostasis responsible for the reactivation of methionine synthase (MTR/MS) activity by catalyzing the reductive methylation of MTR-bound cob(II)alamin (PubMed:17892308). Cobalamin (vitamin B12) forms a complex with MTR to serve as an intermediary in methyl transfer reactions that cycles between MTR-bound methylcob(III)alamin and MTR bound-cob(I)alamin forms, and occasional oxidative escape of the cob(I)alamin intermediate during the catalytic cycle leads to
Cytoplasm
Homocystinuria-megaloblastic anemia, cblE type
An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia. Cells from patients with HMAE fail to incorporate methyltetrahydrofolate into methionine in whole cells, but cell extracts show normal methionine synthase activity in the presence of a reducing agent.
Involved in cobalamin metabolism and trafficking (PubMed:18385497, PubMed:23415655, PubMed:24722857, PubMed:26364851). Plays a role in regulating the biosynthesis and the proportion of two coenzymes, methylcob(III)alamin (MeCbl) and 5'-deoxyadenosylcobalamin (AdoCbl) (PubMed:18385497, PubMed:23415655, PubMed:24722857). Promotes oxidation of cob(II)alamin bound to MMACHC (PubMed:26364851). The processing of cobalamin in the cytosol occurs in a multiprotein complex composed of at least MMACHC, MMA
CytoplasmMitochondrion
Methylmalonic aciduria and homocystinuria, cblD type
An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Clinical features include developmental delay, hyotonia, intellectual disability, seizures, and megaloblastic anemia. Laboratory studies show methylmalonic aciduria and homocystinuria.
Catalyzes the transfer of a methyl group from methylcob(III)alamin (MeCbl) to homocysteine, yielding enzyme-bound cob(I)alamin and methionine in the cytosol (PubMed:16769880, PubMed:17288554, PubMed:27771510). MeCbl is an active form of cobalamin (vitamin B12) used as a cofactor for methionine biosynthesis. Cob(I)alamin form is regenerated to MeCbl by a transfer of a methyl group from 5-methyltetrahydrofolate (PubMed:16769880, PubMed:17288554, PubMed:27771510). The processing of cobalamin in the
Cytoplasm
Homocystinuria-megaloblastic anemia, cblG type
An autosomal recessive inborn error of metabolism resulting from defects in the cobalamin-dependent pathway that converts homocysteine to methionine. It causes delayed psychomotor development, megaloblastic anemia, homocystinuria, and hypomethioninemia.
Cobalamin (vitamin B12) cytosolic chaperone that catalyzes the reductive decyanation of cyanocob(III)alamin (cyanocobalamin, CNCbl) to yield cob(II)alamin and cyanide, using FAD or FMN as cofactors and NADPH as cosubstrate (PubMed:18779575, PubMed:19700356, PubMed:21697092, PubMed:25809485). Cyanocobalamin constitutes the inactive form of vitamin B12 introduced from the diet, and is converted into the active cofactors methylcobalamin (MeCbl) involved in methionine biosynthesis, and 5'-deoxyadeno
Cytoplasm, cytosol
Methylmalonic aciduria and homocystinuria, cblC type
An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). Affected individuals may have developmental, hematologic, neurologic, metabolic, ophthalmologic, and dermatologic clinical findings. Although considered a disease of infancy or childhood, some individuals develop symptoms in adulthood.
Membrane
Lysosomal membrane chaperone required to export cobalamin (vitamin B12) from the lysosome to the cytosol, allowing its conversion to cofactors (PubMed:19136951). Targets ABCD4 transporter from the endoplasmic reticulum to the lysosome (PubMed:27456980). Then forms a complex with lysosomal ABCD4 and cytoplasmic MMACHC to transport cobalamin across the lysosomal membrane (PubMed:25535791). Acts as an adapter protein which plays an important role in mediating and regulating the internalization of t
Endoplasmic reticulum membraneLysosome membraneCell membraneCytoplasmic vesicle, clathrin-coated vesicle
Methylmalonic aciduria and homocystinuria, cblF type
An autosomal recessive disorder of cobalamin metabolism characterized by decreased levels of the coenzymes adenosylcobalamin (AdoCbl) and methylcobalamin (MeCbl). It is due to accumulation of free cobalamin in lysosomes, thus hindering its conversion to cofactors. Clinical features include developmental delay, stomatitis, glossitis, seizures and methylmalonic aciduria responsive to vitamin B12.
Transcriptional coregulator (By similarity). Serves as a scaffold protein, bridging interactions between transcription factors, including THAP11 and ZNF143, and transcriptional coregulators (PubMed:26416877). Involved in control of the cell cycle (PubMed:10629049, PubMed:10779346, PubMed:15190068, PubMed:16624878, PubMed:23629655). Also antagonizes transactivation by ZBTB17 and GABP2; represses ZBTB17 activation of the p15(INK4b) promoter and inhibits its ability to recruit p300 (PubMed:10675337
CytoplasmNucleus
Methylmalonic aciduria and homocystinuria, cblX type
An X-linked recessive metabolic disorder characterized by severely delayed psychomotor development apparent in infancy, failure to thrive, impaired intellectual development, and intractable epilepsy. Additional features may include microcephaly and choreoathetosis.
Variantes genéticas (ClinVar)
125 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
29 vias biológicas associadas aos genes desta condição.
Diagnóstico
Os sinais que médicos procuram e os exames que confirmam
Tratamento e manejo
Remédios, cuidados de apoio e o que precisa acompanhar
Onde tratar no SUS
Hospitais de referência no Brasil e o protocolo oficial do SUS (PCDT)
🇧🇷 Atendimento SUS — Doença do metabolismo da cobalamina
Centros de Referência SUS
21 centros habilitados pelo SUS para Doença do metabolismo da cobalamina
Centros para Doença do metabolismo da cobalamina
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
Hospital de Apoio de Brasília (HAB)
AENW 3 Lote A Setor Noroeste - Plano Piloto, Brasília - DF, 70684-831 · CNES 0010456
Serviço de Referência
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
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
Hospital das Clínicas da UFMG
Av. Prof. Alfredo Balena, 110 - Santa Efigênia, Belo Horizonte - MG, 30130-100 · CNES 2280167
Serviço de Referência
NUPAD / Faculdade de Medicina UFMG
Av. Prof. Alfredo Balena, 189 - 5 andar - Centro, Belo Horizonte - MG, 30130-100 · CNES 2183226
Serviço de Referência
Hospital Universitário João de Barros Barreto
R. dos Mundurucus, 4487 - Guamá, Belém - PA, 66073-000 · CNES 2337878
Serviço de Referência
Hospital de Clínicas da Universidade Federal de Pernambuco
Av. Prof. Moraes Rego, 1235 - Cidade Universitária, Recife - PE, 50670-901 · CNES 2561492
Atenção Especializada
Instituto de Medicina Integral Prof. Fernando Figueira (IMIP)
R. dos Coelhos, 300 - Boa Vista, Recife - PE, 50070-902 · CNES 0000647
Serviço de Referência
Hospital de Clínicas da UFPR
R. Gen. Carneiro, 181 - Alto da Glória, Curitiba - PR, 80060-900 · CNES 2364980
Serviço de Referência
Hospital Universitário Pedro Ernesto (HUPE-UERJ)
Blvd. 28 de Setembro, 77 - Vila Isabel, Rio de Janeiro - RJ, 20551-030 · CNES 2280221
Serviço de Referência
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
Hospital Universitário Onofre Lopes (HUOL)
Av. Nilo Peçanha, 620 - Petrópolis, Natal - RN, 59012-300 · CNES 2408570
Atenção Especializada
Hospital São Lucas da PUCRS
Av. Ipiranga, 6690 - Jardim Botânico, Porto Alegre - RS, 90610-000 · CNES 2232928
Serviço de Referência
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
Hospital Universitário da UFSC (HU-UFSC)
R. Profa. Maria Flora Pausewang - Trindade, Florianópolis - SC, 88036-800 · CNES 2560356
Serviço de Referência
Hospital das Clínicas da FMUSP
R. Dr. Ovídio Pires de Campos, 225 - Cerqueira César, São Paulo - SP, 05403-010 · CNES 2077485
Serviço de Referência
Hospital de Clínicas da UNICAMP
R. Vital Brasil, 251 - Cidade Universitária, Campinas - SP, 13083-888 · CNES 2748223
Serviço de Referência
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
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
UNIFESP / Hospital São Paulo
R. Napoleão de Barros, 715 - Vila Clementino, São Paulo - SP, 04024-002 · CNES 2688689
Serviço de Referência
Dados de DATASUS/CNES, SBGM, ABNeuro e Ministério da Saúde. Sempre confirme a disponibilidade diretamente com o estabelecimento.
Pesquisa ativa
Ensaios clínicos abertos e novidades científicas recentes
Ensaios em destaque
🟢 Recrutando agora
2 pesquisas recrutando participantes. Converse com seu médico sobre a possibilidade de participar.
Outros ensaios clínicos
0 ensaios clínicos encontrados.
Publicações mais relevantes
Stepwise phage resistance and collateral phage susceptibility in Klebsiella pneumoniae.
Carbapenem-resistant Klebsiella pneumoniae (CRKP) is a difficult-to-treat pathogen. Phages recovered by a "stepwise" approach may constitute a cocktail able to prolong retardation of bacterial regrowth. We stepwise recovered three lytic phages (namely P04, P40, and P49) from different families against ST11-KL64 CRKP and created a cocktail that restrained CRKP growth for 15 h. Phage P04 recognized bacterial capsular polysaccharide (CPS). P04/P40-resistant mutants lost the large fragments containing CPS gene due to homologous recombination between two insertion sequences. Through gene cloning and complementation experiments, CPS and lipopolysaccharide (LPS) quantification, and untargeted lipid metabolism assays, deletion of the ugd/wbgU genes alters lipid A modification and outer membrane environment. This change affects the accessibility of an unidentified membrane protein or lipid A itself, which serves as the receptor for P40. P49 recognized bacterial transmembrane protein involved in vitamin B12 transportation. Synergistic antibacterial activity was observed because the three phages recognize different receptors. Notably, P49 also lysed Salmonella enterica, Escherichia coli, Enterobacter ludwigii, and Kluyvera tianfuensis, suggesting new receptors would be exposed when the synthesis of CPS was inhibited, thereby allowing efficient attack by phages originally targeting other species (the 'close-one-door-but-open-another' phenomenon). The conserved structure of BtuB provides a molecular basis for the rare cross-genus activity of P49. Insertion sequences provide a generalized anti-phage defense in encapsulated bacteria. Our findings provide critical insights into the versatile mechanisms underpinning bacteria-phages interactions. Specifically, the collateral susceptibility to phages targeting other bacterial species may provide a novel and highly promising approach for creating clinically viable phage cocktails.
Signal-Level Determinants of Cognitive Decline With PPIs versus H2RAs: Transportome (CBLIF/TCN2) and CHRNA7 Nodes.
Emerging evidence suggests that chronic use of gastric acid-suppressing medications may contribute to neurocognitive decline, yet the underlying mechanisms remain poorly defined. Proton pump inhibitors like omeprazole and histamine-2 receptor antagonists such as ranitidine are widely prescribed for gastrointestinal disorders, but their long-term impact on brain function. Forty-eight male Wistar rats were assigned to six groups receiving either control diet, B12 alone, omeprazole, ranitidine, or co-treatment with B12 for 90 days. Behavioral and cognitive assessments revealed early deficits in the drug-only-treated groups (omeprazole and ranitidine). Notably, B12 ameliorated omeprazole-induced impairments but failed to reverse ranitidine-associated deficits, suggesting divergent neurotoxic pathways. Biochemical profiling included serum B12, homocysteine, cortisol, glucose, insulin, liver enzymes, and neurotransmitter. To complement these in vivo findings, an in silico approach was employed to explore molecular interactions of omeprazole and ranitidine with proteins critical for vitamin B12 transport (CBLIF and TCN2) and cholinergic neurotransmission (CHRNA7). Together, these in vivo and in silico results suggest that omeprazole-induced cognitive decline may involve B12 depletion and other mechanisms, whereas ranitidine likely acts via alternative pathways. This study provides novel mechanistic insights into differential cognitive risks associated with chronic acid-suppressing therapy, with implications for long-term management in populations vulnerable to neurodegeneration.
Modelling CubAm function and regulation in proximal tubular cells using iPSC-derived kidney organoids.
Idiopathic nephrotic syndrome (INS) associated to focal segmental glomeruloesclerosis or minimal change disease is characterized by the presence of heavy levels of proteinuria. Filtrated proteins are normally actively reabsorbed in the proximal tubule by the megalin-cubilin-amnionless complex, located at the apical membrane of the proximal tubule epithelial cells. Megalin has a transmembrane domain but cubilin needs to interact with amnionless to reach the cell membrane in a complex known as CubAm. While megalin has a wide variety of ligands only a few proteins are exclusively transported by binding CubAm; one of those is Apolipoprotein A-I (ApoA-I). The reabsorption of Apolipoprotein A-I (ApoA-I) seems to be impaired in INS but this aspect of INS is difficult to study due to the low expression of CubAm in cultured proximal tubular cells as well as in other in vitro tubular modelling approaches. Here we show that RPTEC/TERT-1 cells cultured in monolayer barely express cubilin and amnionless proteins. In contrast, proximal tubular cells of induced Pluripotent Stem Cells (iPSCs)-derived kidney organoids showed robust expression of CubAm. In addition, protein overload induced an increase of the number of proximal tubular cells expressing cubilin that is reversed when the stimuli is removed. Finally, exogenously added ApoA-I targets cubilin suggesting that the CubAm complex is functional in our iPSCs-derived kidney organoids. Thus, kidney organoids provide a valuable system for modelling specific aspects of INS, including the impact of protein overload on tubular cells and the CubAm-mediated endocytosis of ApoA-I, which is thought to be impaired in these conditions.
Intramuscular Vitamin B12 Treatment in Transcobalamin II Deficiency: Case Series Clinical Outcomes.
Transcobalamin II (TC II) deficiency is a rare autosomal recessive disorder that typically manifests in early infancy. Symptoms include failure to thrive, vomiting, weakness, and pancytopenia. If left undiagnosed and untreated, it can be life-threatening. TC II is crucial for transporting cobalamin (vitamin B12), which plays a vital role in homocysteine and methylmalonic acid metabolism. It serves as a cofactor in neurotransmitter synthesis and protein methylation processes. In this study, we reviewed the clinical presentation, treatment approaches, and long-term outcomes of four patients with confirmed TC II deficiency. All subjects were born to consanguineous parents and exhibited symptoms between birth and four months of age. All patients presented with hematological abnormalities, elevated methylmalonic acid (MMA), and increased total homocysteine (tHcy) levels. Whole Exome Sequencing (WES) confirmed TC II deficiency in all cases, revealing diverse mutation spectra, primarily frameshift mutations (leu320Valfs*51, and IIe330Hisfs*9). No clear genotype-phenotype correlations were observed. The majority of patients were treated with intramuscular hydroxocobalamin (OH-Cbl), resulting in clinical and biochemical improvements. This study underscores the importance of early detection and appropriate management of TC II deficiency to prevent permanent morbidity and potentially fatal outcomes. Regular monitoring of clinical and neurological status, as well as MMA and tHcy levels, is essential to ensure adequate therapy. Intramuscular treatment is the preferred route to prevent neurological deficits and optimal markers normalization.
Analysis of the Association Between the SLC19A1 Genetic Variant (rs1051266) and Autism Spectrum Disorders, Cerebral Folate Deficiency, and Clinical and Laboratory Parameters.
Autism spectrum disorders (ASD) are characterized by clinical heterogeneity and may be associated with cerebral folate deficiency (CFD). Among the causes, folate receptor alpha autoantibodies (FRAA) and variants of the SLC19A1 gene are commonly highlighted. The aim of this study was to analyze the rs1051266 variant of the SLC19A1 gene in patients with ASD and CFD and to determine its relationship with clinical and laboratory parameters. The study included 227 children with ASD, 156 of whom had CFD. FRAA detection, genotyping of the rs1051266 variant, and folate metabolism marker measurement (homocysteine, vitamins B9, B12, B6) were performed. FRAA binding was detected in 39.2% of ASD patients, blocking FRAA in 3.5%, and a specific soluble folate receptor in 13.2%. The 80GA genotype was the most common (46.3%), and homocysteine levels tended to be moderately elevated (upper quartile - 7.0). Significant correlations were found between homocysteine levels and vitamins B9, B12, and B6 (p < 0.05) and between verbal impairments and vitamin B12 (p = 0.043). In ASD and CFD patients, the 80GG genotype was more frequent (p = 0.03) and vitamin B12 levels were elevated (p = 0.021). In the ASD group, correlations were found between the 80AA genotype and demyelination (p = 0.020) and between homocysteine levels and demyelination (p = 0.042). In conclusion, the rs1051266 variant of the SLC19A1 gene modifies the clinical course of ASD. Patients with ASD and CFD exhibited high variability in folate metabolism markers. These findings underline the need for further research on folate transport genetics for personalized prevention and treatment strategies for ASD and CFD.
Publicações recentes
Fatty acids and albumin are transported by distinct mechanisms in the proximal tubule.
Vitamin B(12) uptake across the mycobacterial outer membrane is influenced by membrane permeability in Mycobacterium marinum.
Transmembrane helix 6 of ABCD4 is indispensable for cobalamin transport.
Structural intermediates observed only in intact Escherichia coli indicate a mechanism for TonB-dependent transport.
📚 EuropePMCmostrando 134
Stepwise phage resistance and collateral phage susceptibility in Klebsiella pneumoniae.
Emerging microbes & infectionsSignal-Level Determinants of Cognitive Decline With PPIs versus H2RAs: Transportome (CBLIF/TCN2) and CHRNA7 Nodes.
Molecular nutrition & food researchAirway microbial and metabolic features associated with ICS therapy in COPD.
Frontiers in pharmacologyPatient-reported characteristics of pernicious anaemia: a first step to initiate James Lind Alliance Priority Setting Partnership driven research.
BMC primary careModelling CubAm function and regulation in proximal tubular cells using iPSC-derived kidney organoids.
Experimental cell researchExploring neuropsychiatric manifestations of vitamin B complex deficiencies.
Frontiers in psychiatryFatty acids and albumin are transported by distinct mechanisms in the proximal tubule.
American journal of physiology. Renal physiologyEngineering biology and chemical approaches to the construction of vitamin B12 analogues and antivitamins B12 as probes and therapeutic agents.
Advances in microbial physiologyDapagliflozin combined with methylcobalamin in the treatment of type 2 diabetes mellitus with peripheral neuropathy: a systematic review and meta-analysis.
Frontiers in endocrinologyIntramuscular Vitamin B12 Treatment in Transcobalamin II Deficiency: Case Series Clinical Outcomes.
The application of clinical geneticsCholine in Pediatric Nutrition: Assessing Formula, Fortifiers and Supplements Across Age Groups and Clinical Indications.
NutrientsLongitudinal host-microbiome dynamics of metatranscription identify hallmarks of progression in periodontitis.
MicrobiomeTubular proteinuria due to hereditary endocytic receptor disorder of the proximal tubule: Dent disease and chronic benign proteinuria.
Pediatric nephrology (Berlin, Germany)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 : MNDesigning biocompatible xanthan gum hydrogels for pH-responsive vitamin B12 delivery.
International journal of biological macromoleculesChronic Enteropathy and Vitamins in Dogs.
Animals : an open access journal from MDPIMethylcobalamin protects against liver failure via engaging gasdermin E.
Nature communicationsDissecting the role of vitamin B12 metabolism in craniofacial development through analysis of clinical phenotypes and model organism discoveries.
Differentiation; research in biological diversityVitamin B12 Metabolism: A Network of Multi-Protein Mediated Processes.
International journal of molecular sciencesVitamin B12 Status and Supplementation in Plant-Based Diets.
Food and nutrition bulletinTranscobalamin deficiency - a rare genetic defect in transportation of cobalamin; case report.
Annals of hematologyTranscobalamin receptor antibodies in autoimmune vitamin B12 central deficiency.
Science translational medicineVitamin B12 uptake across the mycobacterial outer membrane is influenced by membrane permeability in Mycobacterium marinum.
Microbiology spectrumSNP-based and haplotype-based genome-wide association on drug dependence in Han Chinese.
BMC genomicsExpression of the cobalamin transporters cubam and MRP1 in the canine ileum-Upregulation in chronic inflammatory enteropathy.
PloS oneTransmembrane helix 6 of ABCD4 is indispensable for cobalamin transport.
Journal of inherited metabolic diseaseMaternal 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 agricultureMetabolomic biomarkers of habitual B vitamin intakes unveil novel differentially methylated positions in the human epigenome.
Clinical epigeneticsBacteroides ovatus accelerates metformin-induced vitamin B12 deficiency in type 2 diabetes patients by accumulating cobalamin.
NPJ biofilms and microbiomesMechanisms Involved in the Neurotoxicity and Abuse Liability of Nitrous Oxide: A Narrative Review.
International journal of molecular sciencesVersatile enzymology and heterogeneous phenotypes in cobalamin complementation type C disease.
iScienceTransferrin-functionalized liposomes loaded with vitamin VB12 for Alzheimer's disease therapy.
International journal of pharmaceuticsSubstrate Specificity and the Direction of Transport in the ABC Transporters ABCD1-3 and ABCD4.
Chemical & pharmaceutical bulletinIschemic 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.
NutrientsClinical, phenotypic and genetic landscape of case reports with genetically proven inherited disorders of vitamin B12 metabolism: A meta-analysis.
Cell reports. MedicineA female case of 5,10-methenyltetrahydrofolate synthetase deficiency with novel neuro-imaging abnormalities.
Brain & developmentInvestigation on a MMACHC mutant from cblC disease: The c.394C>T variant.
Biochimica et biophysica acta. Proteins and proteomicsVitamin 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 SciencesCubilin, the intrinsic factor-vitamin B12 receptor.
Vitamins and hormonesVitamin B12 absorption and malabsorption.
Vitamins and hormonesRenal Expression of CLC-5 and Megalin/Cubilin in Dent-1 Disease With Nonsense Mutations of CLCN5 Gene.
Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology SocietyKnock-Out of Retrovirus Receptor Gene Tva in the Chicken Confers Resistance to Avian Leukosis Virus Subgroups A and K and Affects Cobalamin (Vitamin B12)-Dependent Level of Methylmalonic Acid.
VirusesCobalamin F deficiency in a girl with severe skin hyperpigmentation and a homozygous LMBRD1 variant.
Clinical and experimental dermatologyThe Cerebrospinal Fluid Concentration of Methyltetrahydrofolate and Serum Folate in Children with Developmental Delay, Regression, and/or Refractory Epilepsy.
Neurology IndiaCubilin-, megalin-, and Dab2-dependent transcription revealed by CRISPR/Cas9 knockout in kidney proximal tubule cells.
American journal of physiology. Renal physiologyAnalysis of Six tonB Gene Homologs in Bacteroides fragilis Revealed That tonB3 is Essential for Survival in Experimental Intestinal Colonization and Intra-Abdominal Infection.
Infection and immunityPrenatal diagnosis of combined methylmalonic acidemia and homocystinuria cobalamin C type using clinical exome sequencing and targeted gene analysis.
Molecular genetics & genomic medicineSubclinical maculopathy and retinopathy in transcobalamin deficiency: a 10-year follow-up.
Documenta ophthalmologica. Advances in ophthalmologyStructural intermediates observed only in intact Escherichia coli indicate a mechanism for TonB-dependent transport.
eLifeVitamin B12 status in health and disease: a critical review. Diagnosis of deficiency and insufficiency - clinical and laboratory pitfalls.
Critical reviews in clinical laboratory sciencesCobalamin J disease detected on newborn screening: Novel variant and normal neurodevelopmental course.
American journal of medical genetics. Part ALong-term outcome of a patient with Transcobalamin deficiency caused by the homozygous c.1115_1116delCA mutation in TCN2 gene: a case report.
Italian journal of pediatricsLimited effects of long-term daily cranberry consumption on the gut microbiome in a placebo-controlled study of women with recurrent urinary tract infections.
BMC microbiologyDe Novo Cobalamin Biosynthesis, Transport, and Assimilation and Cobalamin-Mediated Regulation of Methionine Biosynthesis in Mycobacterium smegmatis.
Journal of bacteriologyClinical and molecular findings in 37 Turkish patients with isolated methylmalonic acidemia.
Turkish journal of medical sciencesMechanism of how carbamylation reduces albumin binding to FcRn contributing to increased vascular clearance.
American journal of physiology. Renal physiology[Remethylation disorders: about two cases].
Annales de biologie cliniqueClinical Features and Molecular Genetics of Autosomal Recessive Ataxia in the Turkish Population.
Journal of pediatric neurosciencesNovel CUBN Mutation in a Young Child With Megaloblastic Anemia.
Journal of pediatric hematology/oncologyLessons Learned from Inherited Metabolic Disorders of Sulfur-Containing Amino Acids Metabolism.
The Journal of nutritionMetabolic Serendipities of Expanded Newborn Screening.
GenesDownregulation of megalin, cubilin, ClC-5 and podocin in Fabry nephropathy: potential implications in the decreased effectiveness of enzyme replacement therapy.
Journal of nephrologyCu-catalyzed click conjugation of cobalamin to a BODIPY-based fluorophore: A versatile tool to explore the cellular biology of vitamin B12.
Journal of inorganic biochemistryDelineating the clinical spectrum of isolated methylmalonic acidurias: cblA and mut.
Journal of inherited metabolic diseaseLong Term Culture of Human Kidney Proximal Tubule Epithelial Cells Maintains Lineage Functions and Serves as an Ex vivo Model for Coronavirus Associated Kidney Injury.
Virologica SinicaThe Genetic Epidemiology of Pediatric Pulmonary Arterial Hypertension.
The Journal of pediatrics3'-UTR Polymorphisms of Vitamin B-Related Genes Are Associated with Osteoporosis and Osteoporotic Vertebral Compression Fractures (OVCFs) in Postmenopausal Women.
GenesThe human B12 trafficking protein CblC processes nitrocobalamin.
The Journal of biological chemistryAn altered fecal microbial profiling in rosacea patients compared to matched controls.
Journal of the Formosan Medical Association = Taiwan yi zhiImmunodeficiency and inborn disorders of vitamin B12 and folate metabolism.
Current opinion in clinical nutrition and metabolic careEfficacy of Intravenous Hydroxocobalamin for Treatment of Sodium Methanethiolate Exposure in a Swine Model (Sus scrofa) of Severe Methanethiol Toxicity.
Journal of medical toxicology : official journal of the American College of Medical ToxicologyAn unusually high plasma concentration of homocysteine resulting from a combination of so-called "secondary" etiologies.
Clinical biochemistryDysregulated Gut Homeostasis Observed Prior to the Accumulation of the Brain Amyloid-β in Tg2576 Mice.
International journal of molecular sciencesAssessment of cellular cobalamin metabolism in Gaucher disease.
BMC medical geneticsVitamin B2 and Folate Concentrations are Associated with ARA, EPA and DHA Fatty Acids in Red Blood Cells of Brazilian Children and Adolescents.
NutrientsMucin adsorbed by E. coli can affect neutrophil activation in vitro.
FEBS open bioAssociation between CUBN gene variants, type 2 diabetes and vitamin D concentrations in an elderly Greek population.
The Journal of steroid biochemistry and molecular biologyFlexible Cobamide Metabolism in Clostridioides (Clostridium) difficile 630 Δerm.
Journal of bacteriologyTerminal complement complex C5b-9 reduced megalin and cubilin-mediated tubule proteins uptake in a mouse model of trichloroethylene hypersensitivity syndrome.
Toxicology lettersLysosome-Rich Enterocytes Mediate Protein Absorption in the Vertebrate Gut.
Developmental cellTreatable cause of hereditary spastic paraplegia: eight cases of combined homocysteinaemia with methylmalonic aciduria.
Journal of neurologyGenetic polymorphisms of the cobalamin transport system are associated with idiopathic recurrent implantation failure.
Journal of assisted reproduction and geneticsLoss of abcd4 in zebrafish leads to vitamin B12-deficiency anemia.
Biochemical and biophysical research communicationsAllosteric Regulation of Oligomerization by a B12 Trafficking G-Protein Is Corrupted in Methylmalonic Aciduria.
Cell chemical biologyDouble-sidedness of "laughing gas" on the N-methyl-d-aspartate receptor: A case report of acute psychosis associated with nitrous oxide-induced hyperhomocysteinemia.
Schizophrenia researchPatients with cobalamin G or J defect missed by the current newborn screening program: diagnosis and novel mutations.
Journal of human geneticsRole of pregnancy and obesity on vitamin D status, transport, and metabolism in baboons.
American journal of physiology. Endocrinology and metabolismRenal miR-148b is associated with megalin down-regulation in IgA nephropathy.
Bioscience reportsA Novel Two-Nucleotide Deletion of MMADHC Gene Causing cblD Disease in a Chinese Family.
Chinese medical journalOrchestrated regulation of iron trafficking proteins in the kidney during iron overload facilitates systemic iron retention.
PloS oneCubilin, the Intrinsic Factor-Vitamin B12 Receptor in Development and Disease.
Current medicinal chemistryIntestinal microbiota profiling and predicted metabolic dysregulation in psoriasis patients.
Experimental dermatologyHuman gut Bacteroides capture vitamin B12 via cell surface-exposed lipoproteins.
eLifeMice lacking the transcobalamin-vitamin B12 receptor, CD320, suffer from anemia and reproductive deficits when fed vitamin B12-deficient diet.
Human molecular geneticsImproving the diagnosis of cobalamin and related defects by genomic analysis, plus functional and structural assessment of novel variants.
Orphanet journal of rare diseasesInherited disorders of cobalamin metabolism disrupt nucleocytoplasmic transport of mRNA through impaired methylation/phosphorylation of ELAVL1/HuR.
Nucleic acids researchMild clinical features of isolated methylmalonic acidemia associated with a novel variant in the MMAA gene in two Chinese siblings.
BMC medical geneticsNeutropenia and Increased Mean Corpuscular Volume (MCV) With Abnormal Neurologic Findings: A Case of Cobalamin D Deficiency.
Journal of pediatric hematology/oncologyAmnionless-mediated glycosylation is crucial for cell surface targeting of cubilin in renal and intestinal cells.
Scientific reportsWilson disease and related copper disorders.
Handbook of clinical neurologyMeat Consumption During Pregnancy and Substance Misuse Among Adolescent Offspring: Stratification of TCN2 Genetic Variants.
Alcoholism, clinical and experimental researchBiochemical characteristics of newborns with carnitine transporter defect identified by newborn screening in California.
Molecular genetics and metabolismGenetic polymorphisms and folate status.
Congenital anomaliesClinical or ATPase domain mutations in ABCD4 disrupt the interaction between the vitamin B12-trafficking proteins ABCD4 and LMBD1.
The Journal of biological chemistrySingle allele Lmbrd1 knockout results in cardiac hypertrophy.
Journal of the Formosan Medical Association = Taiwan yi zhiBehavioral alterations are associated with vitamin B12 deficiency in the transcobalamin receptor/CD320 KO mouse.
PloS oneProtein destabilization and loss of protein-protein interaction are fundamental mechanisms in cblA-type methylmalonic aciduria.
Human mutationMaternofetal transport of vitamin B12: role of TCblR/CD320 and megalin.
FASEB journal : official publication of the Federation of American Societies for Experimental BiologyMegaloblastic Anemias: Nutritional and Other Causes.
The Medical clinics of North AmericaVitamin B12 among Vegetarians: Status, Assessment and Supplementation.
NutrientsMethionine synthase and methionine synthase reductase interact with MMACHC and with MMADHC.
Biochimica et biophysica acta. Molecular basis of diseaseABC Transporter Subfamily D: Distinct Differences in Behavior between ABCD1-3 and ABCD4 in Subcellular Localization, Function, and Human Disease.
BioMed research internationalHomocysteine, Infections, Polyamines, Oxidative Metabolism, and the Pathogenesis of Dementia and Atherosclerosis.
Journal of Alzheimer's disease : JADAssociation of KCTD10, MVK, and MMAB polymorphisms with dyslipidemia and coronary heart disease in Han Chinese population.
Lipids in health and diseaseGenetic animal models to decipher the pathogenic effects of vitamin B12 and folate deficiency.
BiochimieLessons in biology from patients with inherited disorders of vitamin B12 and folate metabolism.
BiochimieNeuregulin 1 Promotes Glutathione-Dependent Neuronal Cobalamin Metabolism by Stimulating Cysteine Uptake.
Oxidative medicine and cellular longevityEarly life stress is a risk factor for excessive alcohol drinking and impulsivity in adults and is mediated via a CRF/GABA(A) mechanism.
Stress (Amsterdam, Netherlands)Hydrogen Sulfide--Mechanisms of Toxicity and Development of an Antidote.
Scientific reportsImpact of age at onset and newborn screening on outcome in organic acidurias.
Journal of inherited metabolic diseaseStructural Insights into the MMACHC-MMADHC Protein Complex Involved in Vitamin B12 Trafficking.
The Journal of biological chemistryVitamin B₁₂ deficiency-induced increase of osteoclastic bone resorption caused by abnormal renal resorption of inorganic phosphorus via Napi2a.
Bioscience, biotechnology, and biochemistryStructure of Human B12 Trafficking Protein CblD Reveals Molecular Mimicry and Identifies a New Subfamily of Nitro-FMN Reductases.
The Journal of biological chemistryGenetic modifiers of folate, vitamin B-12, and homocysteine status in a cross-sectional study of the Canadian population.
The American journal of clinical nutritionFunctional signatures of oral dysbiosis during periodontitis progression revealed by microbial metatranscriptome analysis.
Genome medicineTranscobalamin II Deficiency in Four Cases with Novel Mutations.
Turkish journal of haematology : official journal of Turkish Society of HaematologyIn-depth phenotyping of a Donnai-Barrow patient helps clarify proximal tubule dysfunction.
Pediatric nephrology (Berlin, Germany)Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.
EpilepsiaHCFC1 loss-of-function mutations disrupt neuronal and neural progenitor cells of the developing brain.
Human molecular geneticsAssociation of reduced folate carrier-1 (RFC-1) polymorphisms with ischemic stroke and silent brain infarction.
PloS oneAssociation of Transcobalamin II (TCN2) and Transcobalamin II-Receptor (TCblR) Genetic Variations With Cobalamin Deficiency Parameters in Elderly Women.
Biological research for nursingHomocysteine and the pathogenesis of atherosclerosis.
Expert review of clinical pharmacologyImmunohistochemical quantification of the cobalamin transport protein, cell surface receptor and Ki-67 in naturally occurring canine and feline malignant tumors and in adjacent normal tissues.
OncotargetInteractions of vitamin D and the proximal tubule.
Pediatric nephrology (Berlin, Germany)Associações
Organizações que acompanham esta doença — pra ter apoio e orientação
Ainda não temos associações cadastradas para Doença do metabolismo da cobalamina.
É de uma associação que acompanha esta doença? Fale com a gente →
Comunidades
Grupos ativos de quem convive com esta doença aqui no Raras
Ainda não existe comunidade no Raras para Doença do metabolismo da cobalamina
Pacientes, familiares e cuidadores se organizam em comunidades pra compartilhar experiências, fazer perguntas e se apoiar. Você pode ser o primeiro.
Tire suas dúvidas
Perguntas, dicas e experiências compartilhadas aqui na página
Participe da discussão
Faça login para postar dúvidas, compartilhar experiências e interagir com especialistas.
Fazer loginDoenças relacionadas
Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico
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.
- Stepwise phage resistance and collateral phage susceptibility in Klebsiella pneumoniae.
- Signal-Level Determinants of Cognitive Decline With PPIs versus H2RAs: Transportome (CBLIF/TCN2) and CHRNA7 Nodes.
- Modelling CubAm function and regulation in proximal tubular cells using iPSC-derived kidney organoids.
- Intramuscular Vitamin B12 Treatment in Transcobalamin II Deficiency: Case Series Clinical Outcomes.
- Analysis of the Association Between the SLC19A1 Genetic Variant (rs1051266) and Autism Spectrum Disorders, Cerebral Folate Deficiency, and Clinical and Laboratory Parameters.
- Fatty acids and albumin are transported by distinct mechanisms in the proximal tubule.
- Vitamin B(12) uptake across the mycobacterial outer membrane is influenced by membrane permeability in Mycobacterium marinum.
- Transmembrane helix 6 of ABCD4 is indispensable for cobalamin transport.
- Vitamin B12 deficiency.
- Structural intermediates observed only in intact Escherichia coli indicate a mechanism for TonB-dependent transport.
Bases de dados e fontes oficiais
Identificadores e referências canônicas usadas para montar este verbete.
- ORPHA:79171(Orphanet)
- MONDO:0019220(MONDO)
- GARD:18951(GARD (NIH))
- Variantes catalogadas(ClinVar)
- Busca completa no PubMed(PubMed)
- Q55788542(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.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar