PBD4B
MCID: PRX058
MIFTS: 29

Peroxisome Biogenesis Disorder 4b (PBD4B)

Categories: Ear diseases, Eye diseases, Fetal diseases, Genetic diseases, Liver diseases, Mental diseases, Metabolic diseases, Nephrological diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Peroxisome Biogenesis Disorder 4b

MalaCards integrated aliases for Peroxisome Biogenesis Disorder 4b:

Name: Peroxisome Biogenesis Disorder 4b 57 72 29 13 6 70
Pbd4b 57 72
Peroxisome Biogenesis Disorder, Type 4b 39

Characteristics:

OMIM®:

57 (Updated 20-May-2021)
Inheritance:
autosomal recessive
autosomal dominant

Miscellaneous:
appropriate development until 6 months of age
progressive disease leading to death at age 4
autosomal dominant inheritance occurs with a heterozygous mutation in pex6 in conjunction with a 3-prime utr polymorphism in cis causing allelic expression imbalance (aei)


HPO:

31
peroxisome biogenesis disorder 4b:
Inheritance autosomal dominant inheritance autosomal recessive inheritance


Classifications:



Summaries for Peroxisome Biogenesis Disorder 4b

OMIM® : 57 Peroxisome biogenesis disorder-4B (PBD4B) includes the overlapping phenotypes of neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), which represent milder manifestations of the Zellweger syndrome spectrum (ZSS) of peroxisome biogenesis disorders (PBDs). The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy, and visual impairment. Children with the NALD presentation may reach their teens, and those with the IRD presentation may reach adulthood (summary by Waterham and Ebberink, 2012). For a complete phenotypic description and a discussion of genetic heterogeneity of PBD(NALD/IRD), see 601539. Individuals with mutations in the PEX6 gene have cells of complementation group 4 (CG4, equivalent to CG6 and CGC). For information on the history of PBD complementation groups, see 214100. (614863) (Updated 20-May-2021)

MalaCards based summary : Peroxisome Biogenesis Disorder 4b, is also known as pbd4b, and has symptoms including seizures, ataxia and recurrent fevers. An important gene associated with Peroxisome Biogenesis Disorder 4b is PEX6 (Peroxisomal Biogenesis Factor 6). Affiliated tissues include liver and eye, and related phenotypes are macrocephaly and intellectual disability

UniProtKB/Swiss-Prot : 72 Peroxisome biogenesis disorder 4B: A peroxisome biogenesis disorder that includes neonatal adrenoleukodystrophy (NALD) and infantile Refsum disease (IRD), two milder manifestations of the Zellweger disease spectrum. The clinical course of patients with the NALD and IRD presentation is variable and may include developmental delay, hypotonia, liver dysfunction, sensorineural hearing loss, retinal dystrophy and vision impairment. Children with the NALD presentation may reach their teens, while patients with the IRD presentation may reach adulthood. The clinical conditions are often slowly progressive in particular with respect to loss of hearing and vision. The biochemical abnormalities include accumulation of phytanic acid, very long chain fatty acids (VLCFA), di- and trihydroxycholestanoic acid and pipecolic acid.

Symptoms & Phenotypes for Peroxisome Biogenesis Disorder 4b

Human phenotypes related to Peroxisome Biogenesis Disorder 4b:

31 (show all 22)
# Description HPO Frequency HPO Source Accession
1 macrocephaly 31 HP:0000256
2 intellectual disability 31 HP:0001249
3 nystagmus 31 HP:0000639
4 ataxia 31 HP:0001251
5 gait disturbance 31 HP:0001288
6 global developmental delay 31 HP:0001263
7 hepatomegaly 31 HP:0002240
8 hypertelorism 31 HP:0000316
9 short nose 31 HP:0003196
10 sensorineural hearing impairment 31 HP:0000407
11 visual impairment 31 HP:0000505
12 optic atrophy 31 HP:0000648
13 neonatal hypotonia 31 HP:0001319
14 decreased nerve conduction velocity 31 HP:0000762
15 rod-cone dystrophy 31 HP:0000510
16 single transverse palmar crease 31 HP:0000954
17 generalized hypotonia 31 HP:0001290
18 recurrent fever 31 HP:0001954
19 adrenal insufficiency 31 HP:0000846
20 ureterocele 31 HP:0000070
21 decreased liver function 31 HP:0001410
22 seizure 31 HP:0001250

Symptoms via clinical synopsis from OMIM®:

57 (Updated 20-May-2021)
Neurologic Central Nervous System:
intellectual disability
seizures
ataxia
hypotonia
developmental delay
more
Metabolic Features:
recurrent fever

Head And Neck Nose:
small nose

Abdomen Liver:
liver dysfunction
hepatomegaly, mild

Laboratory Abnormalities:
low serum albumin
elevated spinal fluid protein
elevated very long chain fatty acids (vlcfas) in serum and fibroblasts
random serum acth of 100 units
catalase import deficiency

Genitourinary Ureters:
ureterocele, bilateral

Endocrine Features:
adrenal insufficiency (in 1 patient)

Head And Neck Eyes:
nystagmus
hypertelorism
retinitis pigmentosa
optic atrophy, bilateral

Head And Neck Ears:
hearing loss

Head And Neck Head:
large head
widely open fontanels

Growth Other:
growth retardation, postnatal

Genitourinary Kidneys:
oxalate stone, unilateral

Skin Nails Hair Skin:
single transverse palmar crease, bilateral

Clinical features from OMIM®:

614863 (Updated 20-May-2021)

UMLS symptoms related to Peroxisome Biogenesis Disorder 4b:


seizures; ataxia; recurrent fevers

Drugs & Therapeutics for Peroxisome Biogenesis Disorder 4b

Search Clinical Trials , NIH Clinical Center for Peroxisome Biogenesis Disorder 4b

Genetic Tests for Peroxisome Biogenesis Disorder 4b

Genetic tests related to Peroxisome Biogenesis Disorder 4b:

# Genetic test Affiliating Genes
1 Peroxisome Biogenesis Disorder 4b 29 PEX6

Anatomical Context for Peroxisome Biogenesis Disorder 4b

MalaCards organs/tissues related to Peroxisome Biogenesis Disorder 4b:

40
Liver, Eye

Publications for Peroxisome Biogenesis Disorder 4b

Articles related to Peroxisome Biogenesis Disorder 4b:

(show all 20)
# Title Authors PMID Year
1
Allelic Expression Imbalance Promoting a Mutant PEX6 Allele Causes Zellweger Spectrum Disorder. 57 6
29220678 2017
2
Deep sequencing reveals 50 novel genes for recessive cognitive disorders. 57 6
21937992 2011
3
The peroxin Pex6p gene is impaired in peroxisomal biogenesis disorders of complementation group 6. 6 57
11355018 2001
4
Neonatal adrenoleukodystrophy: new cases, biochemical studies, and differentiation from Zellweger and related peroxisomal polydystrophy syndromes. 6 57
3515938 1986
5
Absence of biochemical evidence at an early age delays diagnosis in a patient with a clinically severe peroxisomal biogenesis disorder. 6
26700162 2016
6
Heimler Syndrome Is Caused by Hypomorphic Mutations in the Peroxisome-Biogenesis Genes PEX1 and PEX6. 6
26387595 2015
7
Reproductive genetic counseling challenges associated with diagnostic exome sequencing in a large academic private reproductive genetic counseling practice. 6
26275793 2015
8
RNA splicing. The human splicing code reveals new insights into the genetic determinants of disease. 6
25525159 2015
9
Late-onset Zellweger spectrum disorder caused by PEX6 mutations mimicking X-linked adrenoleukodystrophy. 6
25079577 2014
10
Arginine improves peroxisome functioning in cells from patients with a mild peroxisome biogenesis disorder. 6
24016303 2013
11
Genetics and molecular basis of human peroxisome biogenesis disorders. 57
22871920 2012
12
A founder mutation in the PEX6 gene is responsible for increased incidence of Zellweger syndrome in a French Canadian population. 6
22894767 2012
13
Spectrum of PEX6 mutations in Zellweger syndrome spectrum patients. 6
19877282 2010
14
Rational diagnostic strategy for Zellweger syndrome spectrum patients. 6
19142205 2009
15
Identification of novel mutations and sequence variation in the Zellweger syndrome spectrum of peroxisome biogenesis disorders. 6
19105186 2009
16
Alternative splicing suggests extended function of PEX26 in peroxisome biogenesis. 6
15858711 2005
17
The PEX Gene Screen: molecular diagnosis of peroxisome biogenesis disorders in the Zellweger syndrome spectrum. 6
15542397 2004
18
Genomic structure and identification of 11 novel mutations of the PEX6 (peroxisome assembly factor-2) gene in patients with peroxisome biogenesis disorders. 6
10408779 1999
19
Human peroxisome assembly factor-2 (PAF-2): a gene responsible for group C peroxisome biogenesis disorder in humans. 6
8940266 1996
20
The peroxisome biogenesis disorder group 4 gene, PXAAA1, encodes a cytoplasmic ATPase required for stability of the PTS1 receptor. 6
8670792 1996

Variations for Peroxisome Biogenesis Disorder 4b

ClinVar genetic disease variations for Peroxisome Biogenesis Disorder 4b:

6 (show top 50) (show all 62)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 PEX6 NM_000287.4(PEX6):c.621_882+2del Deletion Pathogenic 8125 rs1554128347 GRCh37: 6:42946005-42946268
GRCh38: 6:42978267-42978530
2 PEX6 PEX6, 269-BP DEL/21-BP INS Indel Pathogenic 8126 GRCh37:
GRCh38:
3 PEX6 NM_000287.4(PEX6):c.1601T>C (p.Leu534Pro) SNV Pathogenic 30195 rs387906809 GRCh37: 6:42936115-42936115
GRCh38: 6:42968377-42968377
4 PEX6 NM_000287.4(PEX6):c.1314_1321del (p.Glu439fs) Deletion Pathogenic 224321 rs267608216 GRCh37: 6:42937452-42937459
GRCh38: 6:42969714-42969721
5 PEX6 NM_000287.4(PEX6):c.2578C>T (p.Arg860Trp) SNV Pathogenic 492968 rs61753230 GRCh37: 6:42933000-42933000
GRCh38: 6:42965262-42965262
6 PEX6 NM_000287.4(PEX6):c.1947del (p.Ile650fs) Deletion Pathogenic 495796 rs267608227 GRCh37: 6:42934534-42934534
GRCh38: 6:42966796-42966796
7 PEX6 NM_000287.4(PEX6):c.2440C>T (p.Arg814Ter) SNV Pathogenic 194165 rs267608241 GRCh37: 6:42933450-42933450
GRCh38: 6:42965712-42965712
8 PEX6 NM_000287.4(PEX6):c.1962-1G>A SNV Pathogenic 550358 rs267608229 GRCh37: 6:42934396-42934396
GRCh38: 6:42966658-42966658
9 PEX6 NM_000287.4(PEX6):c.802_815del (p.Asp268fs) Deletion Pathogenic 555443 rs63749004 GRCh37: 6:42946074-42946087
GRCh38: 6:42978336-42978349
10 PEX6 NM_000287.4(PEX6):c.517del (p.Ser173fs) Deletion Pathogenic 557701 rs61753212 GRCh37: 6:42946372-42946372
GRCh38: 6:42978634-42978634
11 PEX6 NM_000287.4(PEX6):c.2440C>T (p.Arg814Ter) SNV Pathogenic 194165 rs267608241 GRCh37: 6:42933450-42933450
GRCh38: 6:42965712-42965712
12 PEX6 NM_000287.4(PEX6):c.1802G>A (p.Arg601Gln) SNV Pathogenic 198709 rs34324426 GRCh37: 6:42935188-42935188
GRCh38: 6:42967450-42967450
13 PEX6 NM_000287.4(PEX6):c.611C>G (p.Ser204Ter) SNV Pathogenic 973460 GRCh37: 6:42946278-42946278
GRCh38: 6:42978540-42978540
14 PEX6 NM_000287.4(PEX6):c.1234-1G>T SNV Likely pathogenic 557825 rs1554127533 GRCh37: 6:42937540-42937540
GRCh38: 6:42969802-42969802
15 PEX6 NM_000287.4(PEX6):c.1479+2del Deletion Likely pathogenic 557926 rs1554127383 GRCh37: 6:42936610-42936610
GRCh38: 6:42968872-42968872
16 PEX6 NM_000287.4(PEX6):c.1841del (p.Leu614fs) Deletion Likely pathogenic 217426 rs863225083 GRCh37: 6:42935149-42935149
GRCh38: 6:42967411-42967411
17 PEX6 NM_000287.4(PEX6):c.821C>T (p.Pro274Leu) SNV Likely pathogenic 217424 rs61753219 GRCh37: 6:42946068-42946068
GRCh38: 6:42978330-42978330
18 PEX6 NM_000287.4(PEX6):c.273G>A (p.Trp91Ter) SNV Likely pathogenic 498713 rs1010184002 GRCh37: 6:42946616-42946616
GRCh38: 6:42978878-42978878
19 PEX6 NM_000287.4(PEX6):c.2806+1G>A SNV Likely pathogenic 556094 rs751900826 GRCh37: 6:42932527-42932527
GRCh38: 6:42964789-42964789
20 PEX6 NM_000287.4(PEX6):c.2362G>A (p.Val788Met) SNV Likely pathogenic 556244 rs267608240 GRCh37: 6:42933782-42933782
GRCh38: 6:42966044-42966044
21 PEX6 NM_000287.4(PEX6):c.42_43dup (p.Glu15fs) Duplication Likely pathogenic 556911 rs1554128586 GRCh37: 6:42946845-42946846
GRCh38: 6:42979107-42979108
22 PEX6 NM_000287.4(PEX6):c.406delinsAT (p.Pro136fs) Indel Likely pathogenic 557579 rs1554128488 GRCh37: 6:42946483-42946483
GRCh38: 6:42978745-42978745
23 PEX6 NM_000287.4(PEX6):c.383_384GA[1] (p.Glu129fs) Microsatellite Likely pathogenic 555544 rs1554128501 GRCh37: 6:42946501-42946504
GRCh38: 6:42978763-42978766
24 PEX6 NM_000287.4(PEX6):c.311del (p.Gly104fs) Deletion Likely pathogenic 499109 rs61753209 GRCh37: 6:42946578-42946578
GRCh38: 6:42978840-42978840
25 PEX6 NM_000287.4(PEX6):c.1046+1G>A SNV Likely pathogenic 553942 rs1554127968 GRCh37: 6:42942612-42942612
GRCh38: 6:42974874-42974874
26 PEX6 NM_000287.4(PEX6):c.133G>T (p.Glu45Ter) SNV Likely pathogenic 553970 rs1356280167 GRCh37: 6:42946756-42946756
GRCh38: 6:42979018-42979018
27 PEX6 NM_000287.4(PEX6):c.504_505AG[1] (p.Glu169fs) Microsatellite Likely pathogenic 554303 rs1554128461 GRCh37: 6:42946382-42946383
GRCh38: 6:42978644-42978645
28 PEX6 NM_000287.4(PEX6):c.2T>G (p.Met1Arg) SNV Likely pathogenic 555083 rs1554128597 GRCh37: 6:42946887-42946887
GRCh38: 6:42979149-42979149
29 PEX6 NM_000287.4(PEX6):c.2435G>A (p.Arg812Gln) SNV Likely pathogenic 555170 rs61753229 GRCh37: 6:42933455-42933455
GRCh38: 6:42965717-42965717
30 PEX6 NM_000287.4(PEX6):c.2082del (p.Gly695fs) Deletion Likely pathogenic 553235 rs766483138 GRCh37: 6:42934275-42934275
GRCh38: 6:42966537-42966537
31 PEX6 NM_000287.4(PEX6):c.2439dup (p.Arg814fs) Duplication Likely pathogenic 553359 rs1554126955 GRCh37: 6:42933450-42933451
GRCh38: 6:42965712-42965713
32 PEX6 NM_000287.4(PEX6):c.1368-2del Deletion Likely pathogenic 553545 rs1554127415 GRCh37: 6:42936725-42936725
GRCh38: 6:42968987-42968987
33 PEX6 NM_000287.4(PEX6):c.510dup (p.Gly171fs) Duplication Likely pathogenic 551023 rs1491384052 GRCh37: 6:42946378-42946379
GRCh38: 6:42978640-42978641
34 PEX6 NM_000287.4(PEX6):c.2362+1G>A SNV Likely pathogenic 551145 rs1443107232 GRCh37: 6:42933781-42933781
GRCh38: 6:42966043-42966043
35 PEX6 NM_000287.4(PEX6):c.2692del (p.Leu898fs) Deletion Likely pathogenic 551147 rs1554126798 GRCh37: 6:42932642-42932642
GRCh38: 6:42964904-42964904
36 PEX6 NM_000287.4(PEX6):c.1130+2T>C SNV Likely pathogenic 551451 rs1416001981 GRCh37: 6:42941739-42941739
GRCh38: 6:42974001-42974001
37 PEX6 NM_000287.4(PEX6):c.821C>T (p.Pro274Leu) SNV Likely pathogenic 217424 rs61753219 GRCh37: 6:42946068-42946068
GRCh38: 6:42978330-42978330
38 PEX6 NM_000287.4(PEX6):c.462del (p.Leu155fs) Deletion Likely pathogenic 551682 rs1554128476 GRCh37: 6:42946427-42946427
GRCh38: 6:42978689-42978689
39 PEX6 NM_000287.4(PEX6):c.2472-2A>G SNV Likely pathogenic 551909 rs267608242 GRCh37: 6:42933108-42933108
GRCh38: 6:42965370-42965370
40 PEX6 NM_000287.4(PEX6):c.541_543GTG[1] (p.Val182del) Microsatellite Uncertain significance 552092 rs1554128449 GRCh37: 6:42946343-42946345
GRCh38: 6:42978605-42978607
41 PEX6 NM_000287.4(PEX6):c.295C>T (p.Arg99Trp) SNV Uncertain significance 356806 rs772383329 GRCh37: 6:42946594-42946594
GRCh38: 6:42978856-42978856
42 PEX6 NM_000287.4(PEX6):c.2225T>C (p.Leu742Pro) SNV Uncertain significance 552309 rs267608235 GRCh37: 6:42934055-42934055
GRCh38: 6:42966317-42966317
43 PEX6 NM_000287.4(PEX6):c.275_280dup (p.Val92_Arg93dup) Duplication Uncertain significance 552327 rs61752142 GRCh37: 6:42946608-42946609
GRCh38: 6:42978870-42978871
44 PEX6 NM_000287.4(PEX6):c.2626C>T (p.Arg876Trp) SNV Uncertain significance 551183 rs267608246 GRCh37: 6:42932853-42932853
GRCh38: 6:42965115-42965115
45 PEX6 NM_000287.4(PEX6):c.488G>C (p.Arg163Pro) SNV Uncertain significance 550215 rs778791031 GRCh37: 6:42946401-42946401
GRCh38: 6:42978663-42978663
46 PEX6 NM_000287.4(PEX6):c.2356C>T (p.Arg786Trp) SNV Uncertain significance 553552 rs267608239 GRCh37: 6:42933788-42933788
GRCh38: 6:42966050-42966050
47 PEX6 NM_000287.4(PEX6):c.548_550CCT[1] (p.Ser184del) Microsatellite Uncertain significance 552800 rs1554128446 GRCh37: 6:42946336-42946338
GRCh38: 6:42978598-42978600
48 PEX6 NM_000287.4(PEX6):c.202_219del (p.Gly68_Gln73del) Deletion Uncertain significance 553026 rs1162020526 GRCh37: 6:42946670-42946687
GRCh38: 6:42978932-42978949
49 PEX6 NM_000287.4(PEX6):c.254_259dup (p.Ala85_Leu86dup) Duplication Uncertain significance 553033 rs1554128546 GRCh37: 6:42946629-42946630
GRCh38: 6:42978891-42978892
50 PEX6 NM_000287.4(PEX6):c.718G>A (p.Ala240Thr) SNV Uncertain significance 356803 rs886061412 GRCh37: 6:42946171-42946171
GRCh38: 6:42978433-42978433

Expression for Peroxisome Biogenesis Disorder 4b

Search GEO for disease gene expression data for Peroxisome Biogenesis Disorder 4b.

Pathways for Peroxisome Biogenesis Disorder 4b

GO Terms for Peroxisome Biogenesis Disorder 4b

Sources for Peroxisome Biogenesis Disorder 4b

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 20-May-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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