Raras
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Adrenoleucodistrofia neonatal
ORPHA:44CID-10 · E71.3CID-11 · 5A74.YDOENÇA RARA

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).

Mantido por Agente Raras·Colaborar como especialista →

Introdução

O que você precisa saber de cara

📋

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).

Pesquisas ativas
2 ensaios
3 total registrados no ClinicalTrials.gov
Publicações científicas
211 artigos
Último publicado: 2026 Mar 9

Escala de raridade

CLASSIFICAÇÃO ORPHANET · BRASIL 2024
Unknown
Ultra-rara
<1/50k
Muito rara
1/20k
Rara
1/10k
Pouco freq.
1/5k
Incomum
1/2k
Prevalência
0.0
Worldwide
Início
Childhood
+ infancy, neonatal
🏥
SUS: Cobertura mínimaScore: 15%
1 medicamentos CEAFCID-10: E71.3
🇧🇷Dados SUS / DATASUS
PROCEDIMENTOS SIGTAP (7)
0202010279
Dosagem de aminoácidos (erros inatos)metabolic_test
0202010295
Dosagem de ácidos orgânicos na urinagenetic_test
0202010490
Teste de triagem para erros inatos do metabolismonewborn_screening
0202010694
Sequenciamento completo do exoma (WES)rehabilitation
0202080013
Teste do pezinho (triagem neonatal)nutritional
0301070040
Atendimento em reabilitação — doenças raras
+1 outros procedimentos
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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

👁️
Olhos
7 sintomas
🧠
Neurológico
6 sintomas
😀
Face
3 sintomas
👂
Ouvidos
2 sintomas
🦴
Ossos e articulações
1 sintomas
🫘
Rins
1 sintomas

+ 8 sintomas em outras categorias

Características mais comuns

90%prev.
Regressão do desenvolvimento
Muito frequente (99-80%)
90%prev.
Estrabismo
Muito frequente (99-80%)
90%prev.
Atrofia óptica
Muito frequente (99-80%)
90%prev.
Convulsão
Muito frequente (99-80%)
90%prev.
Baixa estatura
Muito frequente (99-80%)
90%prev.
Insuficiência adrenal primária
Muito frequente (99-80%)
29sintomas
Muito frequente (21)
Frequente (8)

Os sintomas variam de pessoa para pessoa. Abaixo estão as 29 características clínicas mais associadas, ordenadas por frequência.

Regressão do desenvolvimentoDevelopmental regression
Muito frequente (99-80%)90%
EstrabismoStrabismus
Muito frequente (99-80%)90%
Atrofia ópticaOptic atrophy
Muito frequente (99-80%)90%
ConvulsãoSeizure
Muito frequente (99-80%)90%
Baixa estaturaShort stature
Muito frequente (99-80%)90%

Linha do tempo da pesquisa

Publicações por ano — veja quando o interesse científico cresceu
Anos de pesquisa1desde 2026
Total histórico211PubMed
Últimos 10 anos13publicações
Pico20253 papers
Linha do tempo
2026Hoje · 2026🧪 1992Primeiro 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

13 genes identificados com associação a esta condição. Padrão de herança: Autosomal recessive.

PEX14Peroxisomal membrane protein PEX14Disease-causing germline mutation(s) inAltamente restrito
FUNÇÃO

Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor (PubMed:24235149, PubMed:28765278, PubMed:9653144). The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm (By similarity). Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (3)
Peroxisomal protein importE3 ubiquitin ligases ubiquitinate target proteinsClass I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Bladder
54.7 TPM
Próstata
39.8 TPM
Útero
31.9 TPM
Brain Frontal Cortex BA9
30.1 TPM
Testículo
29.2 TPM
OUTRAS DOENÇAS (3)
peroxisome biogenesis disorder 13A (Zellweger)Zellweger spectrum disordersobsolete neonatal adrenoleukodystrophy
HGNC:8856UniProt:O75381
PEX10Peroxisome biogenesis factor 10Disease-causing germline mutation(s) inTolerante
FUNÇÃO

E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling (PubMed:24662292). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX10 also regula

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (2)
Peroxisomal protein importE3 ubiquitin ligases ubiquitinate target proteins
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Testículo
33.5 TPM
Glândula adrenal
23.3 TPM
Brain Spinal cord cervical c-1
22.1 TPM
Nervo tibial
20.8 TPM
Fibroblastos
20.1 TPM
OUTRAS DOENÇAS (5)
peroxisome biogenesis disorder 6Bperoxisome biogenesis disorder 6A (Zellweger)autosomal recessive ataxia due to PEX10 deficiencyZellweger spectrum disorders
HGNC:8851UniProt:O60683
PEX6Peroxisomal ATPase PEX6Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling (PubMed:16314507, PubMed:16854980, PubMed:21362118, PubMed:29884772). Specifically recognizes PEX5 monoubiquitinated at 'Cys-11', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel (PubMed:29884772). Extraction by the PEX1-PEX6 AAA ATPase complex is

LOCALIZAÇÃO

Cytoplasm, cytosolPeroxisome membraneCell projection, cilium, photoreceptor outer segment

VIAS BIOLÓGICAS (1)
Peroxisomal protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Fallopian Tube
66.8 TPM
Ovário
64.6 TPM
Cerebelo
61.1 TPM
Cérebro - Hemisfério cerebelar
58.5 TPM
Pituitária
55.1 TPM
OUTRAS DOENÇAS (6)
peroxisome biogenesis disorder 4Bperoxisome biogenesis disorder 4A (Zellweger)peroxisome biogenesis disorder due to PEX6 defectobsolete Heimler syndrome
HGNC:8859UniProt:Q13608
PEX11BPeroxisomal membrane protein 11BDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Involved in peroxisomal proliferation (PubMed:9792670). May regulate peroxisome division by recruiting the dynamin-related GTPase DNM1L to the peroxisomal membrane (PubMed:12618434). Promotes membrane protrusion and elongation on the peroxisomal surface (PubMed:20826455)

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (1)
Class I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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.

EXPRESSÃO TECIDUAL(Ubíquo)
Brain Frontal Cortex BA9
64.0 TPM
Cérebro - Hemisfério cerebelar
63.3 TPM
Linfócitos
57.4 TPM
Testículo
54.2 TPM
Cerebelo
51.1 TPM
OUTRAS DOENÇAS (3)
peroxisome biogenesis disorder 14Bobsolete neonatal adrenoleukodystrophyZellweger spectrum disorders
HGNC:8853UniProt:O96011
PEX2Peroxisome biogenesis factor 2Disease-causing germline mutation(s) inTolerante
FUNÇÃO

E3 ubiquitin-protein ligase component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling (PubMed:24662292). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX2 also regulat

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (3)
Peroxisomal protein importE3 ubiquitin ligases ubiquitinate target proteinsClass I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Linfócitos
32.1 TPM
Cervix Ectocervix
23.1 TPM
Útero
22.3 TPM
Nervo tibial
21.1 TPM
Tireoide
20.4 TPM
OUTRAS DOENÇAS (5)
peroxisome biogenesis disorder 5A (Zellweger)peroxisome biogenesis disorder 5BZellweger spectrum disordersobsolete neonatal adrenoleukodystrophy
HGNC:9717UniProt:P28328
PEX12Peroxisome assembly protein 12Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Component of a retrotranslocation channel required for peroxisome organization by mediating export of the PEX5 receptor from peroxisomes to the cytosol, thereby promoting PEX5 recycling (PubMed:24662292, PubMed:9354782, PubMed:9632816). The retrotranslocation channel is composed of PEX2, PEX10 and PEX12; each subunit contributing transmembrane segments that coassemble into an open channel that specifically allows the passage of PEX5 through the peroxisomal membrane (By similarity). PEX12 also re

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (3)
Peroxisomal protein importE3 ubiquitin ligases ubiquitinate target proteinsClass I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Testículo
12.5 TPM
Fibroblastos
11.2 TPM
Pituitária
10.1 TPM
Glândula adrenal
9.2 TPM
Nervo tibial
9.2 TPM
OUTRAS DOENÇAS (4)
peroxisome biogenesis disorder type 3Bperoxisome biogenesis disorder 3A (Zellweger)Zellweger spectrum disordersobsolete neonatal adrenoleukodystrophy
HGNC:8854UniProt:O00623
PEX26Peroxisome assembly protein 26Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Peroxisomal docking factor that anchors PEX1 and PEX6 to peroxisome membranes (PubMed:12717447, PubMed:12851857, PubMed:16257970, PubMed:16763195, PubMed:16854980, PubMed:21362118). PEX26 is therefore required for the formation of the PEX1-PEX6 AAA ATPase complex, a complex that mediates the extraction of the PEX5 receptor from peroxisomal membrane (PubMed:12717447, PubMed:12851857, PubMed:16257970, PubMed:16763195, PubMed:16854980, PubMed:21362118)

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (2)
Peroxisomal protein importClass I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Linfócitos
12.4 TPM
Intestino delgado
9.0 TPM
Brain Frontal Cortex BA9
9.0 TPM
Cérebro - Hemisfério cerebelar
8.8 TPM
Fibroblastos
8.2 TPM
OUTRAS DOENÇAS (4)
peroxisome biogenesis disorder 7A (Zellweger)peroxisome biogenesis disorder 7BZellweger spectrum disordersobsolete neonatal adrenoleukodystrophy
HGNC:22965UniProt:Q7Z412
PEX13Peroxisomal membrane protein PEX13Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Component of the PEX13-PEX14 docking complex, a translocon channel that specifically mediates the import of peroxisomal cargo proteins bound to PEX5 receptor (PubMed:28765278, PubMed:8858165, PubMed:9653144). The PEX13-PEX14 docking complex forms a large import pore which can be opened to a diameter of about 9 nm (By similarity). Mechanistically, PEX5 receptor along with cargo proteins associates with the PEX14 subunit of the PEX13-PEX14 docking complex in the cytosol, leading to the insertion o

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (3)
Peroxisomal protein importE3 ubiquitin ligases ubiquitinate target proteinsClass I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Tireoide
13.9 TPM
Testículo
13.9 TPM
Fibroblastos
12.2 TPM
Vagina
11.9 TPM
Esôfago - Mucosa
11.2 TPM
OUTRAS DOENÇAS (4)
peroxisome biogenesis disorder 11A (Zellweger)peroxisome biogenesis disorder 11BZellweger spectrum disordersobsolete neonatal adrenoleukodystrophy
HGNC:8855UniProt:Q92968
PEX3Peroxisomal biogenesis factor 3Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Involved in peroxisome biosynthesis and integrity. Assembles membrane vesicles before the matrix proteins are translocated. As a docking factor for PEX19, is necessary for the import of peroxisomal membrane proteins in the peroxisomes

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (2)
ABC transporters in lipid homeostasisClass I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Glândula adrenal
48.7 TPM
Linfócitos
27.7 TPM
Fibroblastos
22.6 TPM
Esôfago - Mucosa
22.3 TPM
Testículo
22.1 TPM
OUTRAS DOENÇAS (4)
peroxisome biogenesis disorder 10Bperoxisome biogenesis disorder 10A (Zellweger)obsolete neonatal adrenoleukodystrophyZellweger spectrum disorders
HGNC:8858UniProt:P56589
PEX1Peroxisomal ATPase PEX1Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Component of the PEX1-PEX6 AAA ATPase complex, a protein dislocase complex that mediates the ATP-dependent extraction of the PEX5 receptor from peroxisomal membranes, an essential step for PEX5 recycling (PubMed:11439091, PubMed:16314507, PubMed:16854980, PubMed:21362118, PubMed:29884772). Specifically recognizes PEX5 monoubiquitinated at 'Cys-11', and pulls it out of the peroxisome lumen through the PEX2-PEX10-PEX12 retrotranslocation channel (PubMed:29884772). Extraction by the PEX1-PEX6 AAA A

LOCALIZAÇÃO

Cytoplasm, cytosolPeroxisome membrane

VIAS BIOLÓGICAS (1)
Peroxisomal protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Ovário
23.8 TPM
Nervo tibial
23.3 TPM
Cervix Endocervix
23.1 TPM
Tireoide
21.9 TPM
Cerebelo
21.8 TPM
OUTRAS DOENÇAS (6)
peroxisome biogenesis disorder 1Bperoxisome biogenesis disorder 1A (Zellweger)peroxisome biogenesis disorder due to PEX1 defectZellweger spectrum disorders
HGNC:8850UniProt:O43933
PEX16Peroxisomal membrane protein PEX16Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Required for peroxisome membrane biogenesis. May play a role in early stages of peroxisome assembly. Can recruit other peroxisomal proteins, such as PEX3 and PMP34, to de novo peroxisomes derived from the endoplasmic reticulum (ER). May function as receptor for PEX3

LOCALIZAÇÃO

Peroxisome membrane

VIAS BIOLÓGICAS (1)
Class I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Pituitária
31.4 TPM
Testículo
30.9 TPM
Tireoide
24.5 TPM
Nervo tibial
23.1 TPM
Brain Spinal cord cervical c-1
22.4 TPM
OUTRAS DOENÇAS (5)
peroxisome biogenesis disorder 8A (Zellweger)peroxisome biogenesis disorder 8BZellweger spectrum disordersobsolete neonatal adrenoleukodystrophy
HGNC:8857UniProt:Q9Y5Y5
PEX19Peroxisomal biogenesis factor 19Disease-causing germline mutation(s) inTolerante
FUNÇÃO

Necessary for early peroxisomal biogenesis. Acts both as a cytosolic chaperone and as an import receptor for peroxisomal membrane proteins (PMPs). Binds and stabilizes newly synthesized PMPs in the cytoplasm by interacting with their hydrophobic membrane-spanning domains, and targets them to the peroxisome membrane by binding to the integral membrane protein PEX3. Excludes CDKN2A from the nucleus and prevents its interaction with MDM2, which results in active degradation of TP53

LOCALIZAÇÃO

CytoplasmPeroxisome membrane

VIAS BIOLÓGICAS (3)
ABC transporters in lipid homeostasisDengue Virus-Host InteractionsClass I peroxisomal membrane protein import
MECANISMO DE DOENÇA

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).

EXPRESSÃO TECIDUAL(Ubíquo)
Tecido adiposo
67.4 TPM
Adipose Visceral Omentum
60.0 TPM
Mama
57.5 TPM
Ovário
56.4 TPM
Artéria tibial
55.3 TPM
OUTRAS DOENÇAS (3)
peroxisome biogenesis disorder 12A (Zellweger)Zellweger spectrum disordersobsolete neonatal adrenoleukodystrophy
HGNC:9713UniProt:P40855
PEX5Peroxisomal targeting signal 1 receptorDisease-causing germline mutation(s) inTolerante
FUNÇÃO

Receptor that mediates peroxisomal import of proteins containing a C-terminal PTS1-type tripeptide peroxisomal targeting signal (SKL-type) (PubMed:11101887, PubMed:11336669, PubMed:12456682, PubMed:16314507, PubMed:17157249, PubMed:17428317, PubMed:21976670, PubMed:26344566, PubMed:7706321, PubMed:7719337, PubMed:7790377). Binds to cargo proteins containing a PTS1 peroxisomal targeting signal in the cytosol, and translocates them into the peroxisome matrix by passing through the PEX13-PEX14 dock

LOCALIZAÇÃO

Cytoplasm, cytosolPeroxisome matrix

VIAS BIOLÓGICAS (1)
Pexophagy
MECANISMO DE DOENÇA

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.

EXPRESSÃO TECIDUAL(Ubíquo)
Testículo
77.7 TPM
Cerebelo
49.0 TPM
Cérebro - Hemisfério cerebelar
48.3 TPM
Pituitária
46.8 TPM
Nervo tibial
44.2 TPM
OUTRAS DOENÇAS (5)
peroxisome biogenesis disorder 2Brhizomelic chondrodysplasia punctata type 5peroxisome biogenesis disorder 2A (Zellweger)Zellweger spectrum disorders
HGNC:9719UniProt:P50542

Variantes genéticas (ClinVar)

266 variantes patogênicas registradas no ClinVar.

🧬 PEX5: NM_001351132.2(PEX5):c.1399_1400del (p.Leu467fs) ()
🧬 PEX5: GRCh38/hg38 12p13.33-11.1(chr12:64621-34650483)x3 ()
🧬 PEX5: NM_001351132.2(PEX5):c.1521_1528delinsA (p.Val508fs) ()
🧬 PEX5: GRCh38/hg38 12p13.33-q13.12(chr12:82453-49847230)x3 ()
🧬 PEX5: NM_001351132.2(PEX5):c.661C>T (p.Gln221Ter) ()
Ver todas no ClinVar

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Publicações mais relevantes

Timeline de publicações
15 papers (10 anos)
#1

Primary Adrenal Insufficiency in Pseudo-Neonatal Adrenoleukodystrophy Case Report.

Journal of clinical research in pediatric endocrinology2026 Mar 09

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.

#2

Detection of a Novel Homozygous PEX5 Stop-Loss Variant Associated with Zellweger Syndrome in a Highly Endogamic Family.

The application of clinical genetics2025

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.

#3

Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.

European journal of endocrinology2025 Apr 30

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.

#4

ACOX1 gain-of-function post-mortem neuropathology is distinct from ACOX1 loss-of-function: case report and literature review.

Free neuropathology2025
#5

Biallelic Deletion of PEX26 Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease.

Molecular syndromology2024 Oct

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

Ver todas no PubMed

📚 EuropePMC34 artigos no totalmostrando 13

2026

Primary Adrenal Insufficiency in Pseudo-Neonatal Adrenoleukodystrophy Case Report.

Journal of clinical research in pediatric endocrinology
2025

ACOX1 gain-of-function post-mortem neuropathology is distinct from ACOX1 loss-of-function: case report and literature review.

Free neuropathology
2025

Detection of a Novel Homozygous PEX5 Stop-Loss Variant Associated with Zellweger Syndrome in a Highly Endogamic Family.

The application of clinical genetics
2025

Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.

European journal of endocrinology
2024

Biallelic Deletion of PEX26 Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease.

Molecular syndromology
2023

The subset of peroxisomal tail-anchored proteins do not reach peroxisomes via ER, instead mitochondria can be involved.

PloS one
2023

Development of a system adapted for the diagnosis and evaluation of peroxisomal disorders by measuring bile acid intermediates.

Brain &amp; development
2022

Pseudo-neonatal Adrenoleukodystrophy: A Rare Peroxisomal Disorder.

Annals of Indian Academy of Neurology
2020

Genome sequencing identifies a rare case of moderate Zellweger spectrum disorder caused by a PEX3 defect: Case report and literature review.

Molecular genetics and metabolism reports
2019

Selective receptor-mediated impairment of growth factor activity in neonatal- and X-linked adrenoleukodystrophy patients.

Journal of pediatric endocrinology &amp; metabolism : JPEM
2018

Long-Term Cholic Acid Treatment in a Patient with Zellweger Spectrum Disorder.

Case reports in gastroenterology
2018

Histologic and ultrastructural features in early and advanced phases of Zellweger spectrum disorder (infantile Refsum disease).

Ultrastructural pathology
2017

Ataxic form of autosomal recessive PEX10-related peroxisome biogenesis disorders with a novel compound heterozygous gene mutation and characteristic clinical phenotype.

Journal of the neurological sciences
Ver todos os 34 no EuropePMC

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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. Primary Adrenal Insufficiency in Pseudo-Neonatal Adrenoleukodystrophy Case Report.
    Journal of clinical research in pediatric endocrinology· 2026· PMID 41797577mais citado
  2. Detection of a Novel Homozygous PEX5 Stop-Loss Variant Associated with Zellweger Syndrome in a Highly Endogamic Family.
    The application of clinical genetics· 2025· PMID 40934063mais citado
  3. Primary adrenal insufficiency caused by pseudo-neonatal adrenoleukodystrophy associated with biallelic ACOX1 mutations.
    European journal of endocrinology· 2025· PMID 40326779mais citado
  4. ACOX1 gain-of-function post-mortem neuropathology is distinct from ACOX1 loss-of-function: case report and literature review.
    Free neuropathology· 2025· PMID 41098161mais citado
  5. Biallelic Deletion of PEX26 Exon 4 in a Boy with Phenotypic Features of both Zellweger Syndrome and Infantile Refsum Disease.
    Molecular syndromology· 2024· PMID 39359950mais citado

Bases de dados e fontes oficiais

Identificadores e referências canônicas usadas para montar este verbete.

  1. ORPHA:44(Orphanet)
  2. MONDO:0018598(MONDO)
  3. Variantes catalogadas(ClinVar)
  4. Busca completa no PubMed(PubMed)
  5. Q16965307(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

Adrenoleucodistrofia neonatal
Compêndio · Raras BR

Adrenoleucodistrofia neonatal

ORPHA:44 · MONDO:0018598
🇧🇷 Brasil SUS
CEAF
1AElivaldogene autotemcel
Geral
Prevalência
Unknown
Herança
Autosomal recessive
CID-10
E71.3 · Distúrbios do metabolismo de ácidos graxos
CID-11
Ensaios
2 ativos
Início
Childhood, Infancy, Neonatal
Prevalência
0.0 (Worldwide)
MedGen
UMLS
C0282525
EuropePMC
Wikidata
Papers 10a
DiscussaoAtiva

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