OBSOLETO. A adrenoleucodistrofia neonatal (NALD) é a variante de gravidade intermediária do espectro da síndrome PBD-Zellweger (PBD-ZSS), caracterizada por hipotonia, leucodistrofia e deficiências visuais e auditivas neurossensoriais. A sobreposição fenotípica é observada entre NALD e doença de Refsum infantil (IRD).
Introdução
O que você precisa saber de cara
A adrenoleucodistrofia neonatal é uma condição genética rara que se manifesta nas primeiras etapas da infância. A criança afetada costuma apresentar fraqueza muscular acentuada, atraso no desenvolvimento, convulsões e dificuldades na visão e na audição. O quadro tem herança autossômica recessiva e ocorre devido a mutações genéticas que afetam o funcionamento das células. A condição não consta na lista oficial de PCDTs de doenças raras do Ministério da Saúde nem possui medicamentos específicos dispensados pelo SUS. O acompanhamento é voltado ao controle dos sintomas e ao suporte das necessidades do paciente.
OBSOLETO. A adrenoleucodistrofia neonatal (NALD) é a variante de gravidade intermediária do espectro da síndrome PBD-Zellweger (PBD-ZSS), caracterizada por hipotonia, leucodistrofia e deficiências visuais e auditivas neurossensoriais. A sobreposição fenotípica é observada entre NALD e doença de Refsum infantil (IRD).
Escala de raridade
<1/50kMuito rara
1/20kRara
1/10kPouco freq.
1/5kIncomum
1/2k
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Entender a doença
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Preparando trilha educativa...
Sinais e sintomas
O que aparece no corpo e com que frequência cada sintoma acontece
Partes do corpo afetadas
+ 8 sintomas em outras categorias
Características mais comuns
Os sintomas variam de pessoa para pessoa. Abaixo estão as 29 características clínicas mais associadas, ordenadas por frequência.
Linha do tempo da pesquisa
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Genética e causas
O que está alterado no DNA e como passa nas famílias
Genes associados
13 genes identificados com associação a esta condição. Padrão de herança: Autosomal recessive.
Peroxisome biogenesis disorder complementation group K
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 7
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 4
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder 14B
An autosomal recessive peroxisome biogenesis disorder characterized clinically by mild intellectual disability, congenital cataracts, progressive hearing loss, and polyneuropathy. Additionally, recurrent migraine-like episodes following mental stress or physical exertion, not a common feature in peroxisome disorders, are observed.
Peroxisome biogenesis disorder complementation group 5
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 3
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 8
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 13
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 12
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 1
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 9
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder complementation group 14
A peroxisomal disorder arising from a failure of protein import into the peroxisomal membrane or matrix. The peroxisome biogenesis disorders (PBD group) are genetically heterogeneous with at least 14 distinct genetic groups as concluded from complementation studies. Include disorders are: Zellweger syndrome (ZWS), neonatal adrenoleukodystrophy (NALD), infantile Refsum disease (IRD), and classical rhizomelic chondrodysplasia punctata (RCDP). ZWS, NALD and IRD are distinct from RCDP and constitute a clinical continuum of overlapping phenotypes known as the Zellweger spectrum (PBD-ZSS).
Peroxisome biogenesis disorder 2A
A fatal peroxisome biogenesis disorder belonging to the Zellweger disease spectrum and characterized clinically by severe neurologic dysfunction with profound psychomotor retardation, severe hypotonia and neonatal seizures, craniofacial abnormalities, liver dysfunction, and biochemically by the absence of peroxisomes. Additional features include cardiovascular and skeletal defects, renal cysts, ocular abnormalities, and hearing impairment. Most severely affected individuals with the classic form of the disease (classic Zellweger syndrome) die within the first year of life.
Variantes genéticas (ClinVar)
266 variantes patogênicas registradas no ClinVar.
Vias biológicas (Reactome)
6 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 — Adrenoleucodistrofia neonatal
Selecione um estado ou use sua localização para ver resultados.
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
Pesquisa e ensaios clínicos
Nenhum ensaio clínico registrado para esta condição.
Publicações mais relevantes
Primary Adrenal Insufficiency in Pseudo-Neonatal Adrenoleukodystrophy Case Report.
Primary adrenal insufficiency (PAI) in childhood is a rare and potentially life-threatening condition that may arise from defects in adrenal steroidogenesis, adrenal dysgenesis, ACTH resistance, autoimmune mechanisms, or inherited metabolic disorders. Among the latter, peroxisomal dysfunctions represent a rare cause. Although X-linked adrenoleukodystrophy is a well-recognized etiology, adrenal involvement in other peroxisomal diseases, such as ACOX1 deficiency, remains poorly defined. We report a three-year-old girl with global developmental delay, epilepsy, bilateral sensorineural hearing loss, and progressive neurological regression. Biochemical analyses revealed abnormal plasma very-long-chain fatty acids profile, suggesting a peroxisomal disorder. Whole-exome sequencing identified a homozygous pathogenic variant (c.1478+2T>A) in ACOX1, confirming the diagnosis of pseudo-neonatal adrenoleukodystrophy. During hospitalization for a urinary tract infection, endocrine evaluation revealed markedly elevated plasma ACTH (529 pg/mL) and low serum cortisol (8.62 µg/dL), while Na, K, and PRA were within normal limits. Adrenal imaging was consistent with atrophy. Hydrocortisone replacement was initiated with good clinical response. Notably, the patient had no classical signs of adrenal failure such as hyperpigmentation or electrolyte imbalance. This case provides additional evidence that ACOX1-related Pseudo-neonatal adrenoleukodystrophy may be associated with variable adrenal involvement, expanding the phenotypic spectrum of the disorder. The absence of typical clinical manifestations highlights the importance of routine hormonal screening in children with peroxisomal diseases, even in the absence of overt adrenal symptoms. Early recognition of endocrine dysfunction can prevent life-threatening adrenal crises and offers valuable insight into the broader pathophysiology of peroxisomal β-oxidation disorders.
Detection of a Novel Homozygous PEX5 Stop-Loss Variant Associated with Zellweger Syndrome in a Highly Endogamic Family.
Zellweger syndrome (ZS) is a heterogeneous group of clinical conditions that commonly manifest with neurodevelopmental delay, multiple neurological abnormalities, visual and auditory impairments, and adrenocortical dysfunction. ZS is an autosomal recessive peroxisomal disorder resulting from mutations in one of over 13 identified genes. We report the case of a male child with episodic seizures starting at 18 days of life, followed by neurodevelopmental delay and neuroimaging findings of asymmetric polymicrogyria and cortical abnormalities. His healthy parents were consanguineous, and notably, a brother, who passed away at the age of 5 years-old, had epilepsy and adrenoleukodystrophy. Exome sequencing allowed the identification of a novel stop-loss homozygous variant in the PEX5 gene in the index case. The phenotype associated to this gene, Zellweger syndrome, as well as the inheritance mechanism, is consistent with that observed in both the patient and his brother.
Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.
Peroxisomal fatty acyl-CoA oxidase 1, encoded by ACOX1, initiates and limits the rate of beta-oxidation of very long-chain fatty acids (VLCFA). Biallelic ACOX1 mutations cause pseudo-neonatal adrenoleukodystrophy (PNALD). Primary adrenal insufficiency (PAI) has not been clearly characterized in the 34 PNALD patients reported to date. Characterizing PAI in a patient and her cousin with PNALD. Clinical data were recorded, and molecular etiologies were investigated using next-generation sequencing panels and 750K microarray. Plasma steroids and VLCFAs were measured via mass spectrometry. A 1.5-year-old female patient was evaluated for PAI due to hyperpigmentation, hypoglycemia, hyponatremia and hyperkalemia. She had a history of severe neonatal-onset hypotonia, seizures, psychomotor/developmental delay, and neurological regression. Molecular studies revealed a homozygous deletion encompassing exons 13 and 14 of the ACOX1 gene. Biochemical analysis revealed accumulation of saturated VLCFA. Cranial magnetic resonance imaging showed T2 high-intensity areas in bilateral centrum semiovale, basal ganglia, brainstem and cerebellar white matter. High plasma ACTH, low cortisol and steroid precursors along with high plasma renin activity were compatible with a PAI other than congenital adrenal hyperplasia (non-CAH). Abdominal computerized tomography demonstrated bilateral adrenal atrophy. The cousin of the patient with PNALD developed non-CAH PAI at 7 months of age. Adrenal insufficiency should be considered in the phenotypic spectrum of peroxisomal disorders. Fatty acyl-CoA oxidase 1 deficiency may emerge as a peroxisomal etiology of non-CAH PAI.
ACOX1 gain-of-function post-mortem neuropathology is distinct from ACOX1 loss-of-function: case report and literature review.
Biallelic Deletion of PEX26 Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease.
Peroxisome biogenesis disorders (PBDs) encompass a group of diseases marked by clinical and genetic heterogeneity. Phenotypes linked to PBDs include Zellweger syndrome, neonatal adrenoleukodystrophy, infantile Refsum disease (IRD), rhizomelic chondrodysplasia punctata type 1, and Heimler syndrome. PBD phenotypes manifest through hypotonia, developmental delay, facial dysmorphism, seizures, liver dysfunction, sensorineural hearing loss, and retinal dystrophy. The proband underwent comprehensive clinical evaluation, followed by whole-exome sequencing (WES) coupled with copy number analysis (CNV), aimed at identifying potential disease-causing variants aligning with the observed phenotype. Our findings detail an individual exhibiting developmental delay, hearing loss, visual impairment, hepatomegaly, and splenomegaly, attributed to a biallelic deletion of exon 4 in the PEX26 gene. The WES analysis of the index case did not uncover any pathogenic/likely pathogenic single-nucleotide variations that could account for the observed clinical findings. However, the CNV data derived from WES revealed a homozygous deletion in exon 4 of the PEX26 gene (NM_001127649.3), providing a plausible explanation for the patient's clinical features. The exon 4 region of PEX26 encodes the transmembrane domain of the protein. The transmembrane domain plays a crucial role in anchoring the protein within lipid bilayers, and its absence can disrupt proper localization and functioning. As a result, this structural alteration may impact the protein's ability to facilitate essential cellular processes related to peroxisome biogenesis and function. The index patient, which presented with hearing loss, retinal involvement and hepatic dysfunction in adolescence age, has atypical clinical course that can be considered unusual for Zellweger syndrome (ZS) and IRD phenotypes, and its rare genotypic data (in-frame single exon deletion) expands the PBD disease spectrum. This study revealed for the first time that PEX26 protein transmembrane domain loss exhibits an unusual course with clinical findings of IRD and ZS phenotypes. WES studies, incorporating CNV analyses, empower the identification of novel genetic alterations in genes seldom associated with gross deletion/duplication variations, such as those in the PEX26 gene. This not only enhances diagnostic rates in rare diseases but also contributes to broadening the spectrum of causal mutations.
Publicações recentes
Primary Adrenal Insufficiency in Pseudo-Neonatal Adrenoleukodystrophy Case Report.
ACOX1 gain-of-function post-mortem neuropathology is distinct from ACOX1 loss-of-function: case report and literature review.
Detection of a Novel Homozygous PEX5 Stop-Loss Variant Associated with Zellweger Syndrome in a Highly Endogamic Family.
Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.
Biallelic Deletion of PEX26 Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease.
📚 EuropePMC34 artigos no totalmostrando 13
Primary Adrenal Insufficiency in Pseudo-Neonatal Adrenoleukodystrophy Case Report.
Journal of clinical research in pediatric endocrinologyACOX1 gain-of-function post-mortem neuropathology is distinct from ACOX1 loss-of-function: case report and literature review.
Free neuropathologyDetection of a Novel Homozygous PEX5 Stop-Loss Variant Associated with Zellweger Syndrome in a Highly Endogamic Family.
The application of clinical geneticsPrimary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.
European journal of endocrinologyBiallelic Deletion of PEX26 Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease.
Molecular syndromologyThe subset of peroxisomal tail-anchored proteins do not reach peroxisomes via ER, instead mitochondria can be involved.
PloS oneDevelopment of a system adapted for the diagnosis and evaluation of peroxisomal disorders by measuring bile acid intermediates.
Brain & developmentPseudo-neonatal Adrenoleukodystrophy: A Rare Peroxisomal Disorder.
Annals of Indian Academy of NeurologyGenome sequencing identifies a rare case of moderate Zellweger spectrum disorder caused by a PEX3 defect: Case report and literature review.
Molecular genetics and metabolism reportsSelective receptor-mediated impairment of growth factor activity in neonatal- and X-linked adrenoleukodystrophy patients.
Journal of pediatric endocrinology & metabolism : JPEMLong-Term Cholic Acid Treatment in a Patient with Zellweger Spectrum Disorder.
Case reports in gastroenterologyHistologic and ultrastructural features in early and advanced phases of Zellweger spectrum disorder (infantile Refsum disease).
Ultrastructural pathologyAtaxic form of autosomal recessive PEX10-related peroxisome biogenesis disorders with a novel compound heterozygous gene mutation and characteristic clinical phenotype.
Journal of the neurological sciencesAssociações
Organizações que acompanham esta doença — pra ter apoio e orientação
Associação brasileira dedicada a Adrenoleucodistrofia.
Doença com base genética
Um médico geneticista pode ajudar no diagnóstico de Adrenoleucodistrofia neonatal e no aconselhamento genético da família.
Doenças relacionadas
Doenças com sintomas parecidos — ajudam quem ainda está buscando diagnóstico
Perguntas frequentes
O que as famílias mais perguntam sobre esta doença — cada resposta com a fonte de onde saiu
Sim, a adrenoleucodistrofia neonatal apresenta um padrão de herança autossômica recessiva. A criança herda variantes patogênicas em genes peroxissomais de ambos os genitores.
Referências
Fontes citadas no texto, publicações do grafo e bases de dados usadas neste verbete
5 publicações do grafo RarasNet (PubMed) · 5 bases de dados. Títulos, periódicos e PMIDs vêm direto da fonte, sem intermediação de IA.
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.
Citar este verbete
Raras. (s.d.). Adrenoleucodistrofia neonatal. Em Raras — Enciclopédia de Doenças Raras do Brasil. https://raras.org/doenca/adrenoleucodistrofia-neonatal
Formato APA. Conteúdo sob CC BY 4.0 — reuso livre com atribuição.
Conteúdo mantido por Agente Raras · Médicos e pesquisadores podem colaborar
Adrenoleucodistrofia neonatal
📋 Origem dos dados
Esta página agrega dados de fontes públicas e oficiais. Dados sobre cobertura no SUS (PCDT, CEAF) são verificados ativamente por agente proativo (ver badge no infobox). Demais dados têm atribuição de fonte + data da última sincronização — clique para abrir o original.
- Doença rara (ontologia)
- fonte: Orphanet
- Identificador unificado
- fonte: MONDO
- Codificação WHO/SUS
- fonte: WHO ICD-10 / DATASUS
- CID-11 (futuro)
- fonte: WHO ICD-11
- Dado público estruturado
- fonte: Wikidata
