DBPD
MCID: DBF001
MIFTS: 60

D-Bifunctional Protein Deficiency (DBPD)

Categories: Genetic diseases, Metabolic diseases, Rare diseases
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Aliases & Classifications for D-Bifunctional Protein Deficiency

MalaCards integrated aliases for D-Bifunctional Protein Deficiency:

Name: D-Bifunctional Protein Deficiency 57 11 19 42 73 12 53 14 75
Bifunctional Peroxisomal Enzyme Deficiency 42 28 5 71
17-Beta-Hydroxysteroid Dehydrogenase Iv Deficiency 57 19 42
Peroxisomal Bifunctional Enzyme Deficiency 57 19 42
Pbfe Deficiency 57 19 42
Dbp Deficiency 57 19 42
Bifunctional Enzyme Deficiency 19 58
Pseudo-Zellweger Syndrome 42 71
Protein Deficiency, D-Bifunctional 38
Zellweger-Like Syndrome 42
Dbpd 73

Characteristics:


Inheritance:

Autosomal recessive 57

Age Of Onset:

Bifunctional Enzyme Deficiency: Infancy 58

Age Of Death:

Bifunctional Enzyme Deficiency: early childhood,infantile 58

OMIM®:

57 (Updated 24-Oct-2022)
Miscellaneous:
onset in infancy
prevalence of 1 in 100,000
early death, usually before age 2 years


Classifications:

Orphanet: 58  
Inborn errors of metabolism


Summaries for D-Bifunctional Protein Deficiency

MedlinePlus Genetics: 42 D-bifunctional protein deficiency is a disorder that causes deterioration of nervous system functions (neurodegeneration) beginning in infancy. Newborns with D-bifunctional protein deficiency have weak muscle tone (hypotonia) and seizures. Most babies with this condition never acquire any developmental skills. Some may reach very early developmental milestones such as the ability to follow movement with their eyes or control their head movement, but they experience a gradual loss of these skills (developmental regression) within a few months. As the condition gets worse, affected children develop exaggerated reflexes (hyperreflexia), increased muscle tone (hypertonia), more severe and recurrent seizures (epilepsy), and loss of vision and hearing. Most children with D-bifunctional protein deficiency do not survive past the age of 2. A small number of individuals with this disorder are somewhat less severely affected. They may acquire additional basic skills, such as voluntary hand movements or unsupported sitting, before experiencing developmental regression, and they may survive longer into childhood than more severely affected individuals.Individuals with D-bifunctional protein deficiency may have unusual facial features, including a high forehead, widely spaced eyes (hypertelorism), a lengthened area between the nose and mouth (philtrum), and a high arch of the hard palate at the roof of the mouth. Affected infants may also have an unusually large space between the bones of the skull (fontanelle). An enlarged liver (hepatomegaly) occurs in about half of affected individuals. Because these features are similar to those of another disorder called Zellweger syndrome (part of a group of disorders called the Zellweger spectrum), D-bifunctional protein deficiency is sometimes called pseudo-Zellweger syndrome.

MalaCards based summary: D-Bifunctional Protein Deficiency, also known as bifunctional peroxisomal enzyme deficiency, is related to peroxisomal acyl-coa oxidase deficiency and zellweger spectrum disorder. An important gene associated with D-Bifunctional Protein Deficiency is HSD17B4 (Hydroxysteroid 17-Beta Dehydrogenase 4), and among its related pathways/superpathways are Metabolism and Fatty acid metabolism. The drugs Rituximab and Fludarabine have been mentioned in the context of this disorder. Affiliated tissues include liver, kidney and adrenal cortex, and related phenotypes are macrocephaly and failure to thrive

OMIM®: 57 D-bifunctional protein deficiency is a disorder of peroxisomal fatty acid beta-oxidation. See also peroxisomal acyl-CoA oxidase deficiency (264470), caused by mutation in the ACOX1 gene (609751) on chromosome 17q25. The clinical manifestations of these 2 deficiencies are similar to those of disorders of peroxisomal assembly, including X-linked adrenoleukodystrophy (ALD; 300100), Zellweger cerebrohepatorenal syndrome (see 214100) and neonatal adrenoleukodystrophy (NALD; see 601539) (Watkins et al., 1995). DBP deficiency has been classified into 3 subtypes depending upon the deficient enzyme activity. Type I is a deficiency of both 2-enoyl-CoA hydratase and 3-hydroxyacyl-CoA dehydrogenase; type II is a deficiency of hydratase activity alone; and type III is a deficiency of dehydrogenase activity alone. Virtually all patients with types I, II, and III have a severe phenotype characterized by infantile-onset of hypotonia, seizures, and abnormal facial features, and most die before age 2 years. McMillan et al. (2012) proposed a type IV deficiency on the basis of less severe features; these patients have a phenotype reminiscent of Perrault syndrome (PRLTS1; 233400). Pierce et al. (2010) noted that Perrault syndrome and DBP deficiency overlap clinically and suggested that DBP deficiency may be underdiagnosed. (261515) (Updated 24-Oct-2022)

Orphanet: 58 A rare peroxisomal beta-oxidation disorder characterized by deficiency of peroxisomal D-bifunctional protein, type 1 being caused by deficiency of both dehydrogenase and hydratase activities of the enzyme, and types 2 and 3 by hydratase or dehydrogenase deficiency alone, while type 4 is due to compound heterozygous mutations affecting both units and represents a clinically milder phenotype. Types 1-3 are typically fatal in infancy. Patients present with early onset of generalized hypotonia, seizures, severe global developmental delay, craniofacial dysmorphism (large fontanel, high forehead, hypertelorism, epicanthal folds) and elevated plasma very long chain fatty acids. Variable features include hepatomegaly, polymicrogyria, and cerebral white matter abnormalities, among others.

GARD: 19 D-bifunctional protein deficiency (DBP deficiency) is a genetic disorder that affects the ability of the body to effectively break down fat from our diet. It is typically characterized by hypotonia (low muscle tone) and seizures in the newborn period. Other symptoms include unusual facial features and an enlarged liver (hepatomegaly). DBP deficiency is caused by genetic changes in the HSD17B4 gene and is inherited in an autosomal recessive manner.

Disease Ontology: 11 A peroxisomal disease characterized by, in severe cases, infantile-onset of hypotonia, seizures, and abnormal facial features with most dieing before age 2 years that has material basis in homozygous or compound heterozygous mutation in the HSD17B4 gene on chromosome 5q2.

UniProtKB/Swiss-Prot: 73 Disorder of peroxisomal fatty acid beta-oxidation.

Wikipedia: 75 D-Bifunctional protein deficiency is an autosomal recessive peroxisomal fatty acid oxidation disorder.... more...

Related Diseases for D-Bifunctional Protein Deficiency

Diseases related to D-Bifunctional Protein Deficiency via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 70)
# Related Disease Score Top Affiliating Genes
1 peroxisomal acyl-coa oxidase deficiency 31.2 HSD17B4 ELOVL1 ACOX3 ACOX2 ACOX1 ABCD3
2 zellweger spectrum disorder 30.6 PEX6 PEX1
3 peroxisome biogenesis disorder 1a 30.5 PEX6 PEX1
4 perrault syndrome 30.3 SCP2 PPP4R4 LARS2 HSD17B4 DHRS11
5 leukodystrophy 30.1 PEX6 ACOX1 ABCD3 ABCD1
6 neonatal adrenoleukodystrophy 30.1 SCP2 PEX6 PEX1 EHHADH ACOX1
7 peroxisomal disease 29.9 SCP2 PEX6 PEX1 HSD17B4 HADHB ACOX1
8 sensorineural hearing loss 29.8 PEX6 PEX1 LARS2 HSD17B4 ACOX1
9 46 xx gonadal dysgenesis 29.5 LARS2 HSD17B4
10 peroxisome biogenesis disorder 1b 29.4 SCP2 PEX6 PEX1 HSD17B4 ACOX1 ABCD3
11 adrenoleukodystrophy 29.0 PEX6 PEX1 HSD17B4 HADHB ELOVL1 EHHADH
12 peroxisomal biogenesis disorder 28.5 SCP2 PEX6 PEX1 HSD17B4 ELOVL1 EHHADH
13 zellweger syndrome 28.2 SUOX SCP2 PEX6 PEX1 HSD17B4 HADHB
14 alpha-methylacetoacetic aciduria 11.5
15 zellweger-like syndrome without peroxisomal anomalies 11.5
16 hypotonia 10.5
17 perrault syndrome 1 10.4
18 neuropathy 10.3
19 long-chain 3-hydroxyacyl-coa dehydrogenase deficiency 10.2 HADHB HADH
20 aceruloplasminemia 10.2
21 polymicrogyria 10.2
22 visual epilepsy 10.2
23 optic nerve disease 10.2
24 hypogonadism 10.2
25 peripheral nervous system disease 10.2
26 pathologic nystagmus 10.2
27 rare genetic deafness 10.2
28 syndromic x-linked intellectual disability type 10 10.2 HADH DHRS11
29 heimler syndrome 1 10.1 PEX6 PEX1
30 nijmegen breakage syndrome 10.1
31 spastic paraplegia 46, autosomal recessive 10.1 SCP2 PEX6
32 mitochondrial trifunctional protein deficiency 10.1 HADHB HADH EHHADH
33 carnitine palmitoyltransferase i deficiency 10.1 HADHB HADH
34 retinal dystrophy with leukodystrophy 10.1 ACOX1 ABCD1
35 carnitine deficiency, systemic primary 10.1 HADHB HADH
36 ascites, chylous 10.0
37 3-methylglutaconic aciduria, type iii 10.0
38 retinitis pigmentosa 10.0
39 schizencephaly 10.0
40 congenital hemidysplasia with ichthyosiform erythroderma and limb defects 10.0
41 premature ovarian failure 7 10.0
42 developmental and epileptic encephalopathy 7 10.0
43 acatalasemia 10.0
44 west syndrome 10.0
45 lissencephaly 10.0
46 early infantile epileptic encephalopathy 10.0
47 rickets 10.0
48 premature menopause 10.0
49 respiratory failure 10.0
50 clubfoot 10.0

Graphical network of the top 20 diseases related to D-Bifunctional Protein Deficiency:



Diseases related to D-Bifunctional Protein Deficiency

Symptoms & Phenotypes for D-Bifunctional Protein Deficiency

Human phenotypes related to D-Bifunctional Protein Deficiency:

30 (show top 50) (show all 58)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 macrocephaly 30 Very rare (1%) HP:0000256
2 failure to thrive 30 Very rare (1%) HP:0001508
3 frontal bossing 30 Very rare (1%) HP:0002007
4 nystagmus 30 Very rare (1%) HP:0000639
5 high palate 30 Very rare (1%) HP:0000218
6 hearing impairment 30 Very rare (1%) HP:0000365
7 global developmental delay 30 Very rare (1%) HP:0001263
8 splenomegaly 30 Very rare (1%) HP:0001744
9 hepatomegaly 30 Very rare (1%) HP:0002240
10 depressed nasal bridge 30 Very rare (1%) HP:0005280
11 hypertelorism 30 Very rare (1%) HP:0000316
12 neonatal hypotonia 30 Very rare (1%) HP:0001319
13 decreased nerve conduction velocity 30 Very rare (1%) HP:0000762
14 strabismus 30 Very rare (1%) HP:0000486
15 retrognathia 30 Very rare (1%) HP:0000278
16 micrognathia 30 Very rare (1%) HP:0000347
17 low-set ears 30 Very rare (1%) HP:0000369
18 hepatic steatosis 30 Very rare (1%) HP:0001397
19 elevated hepatic transaminase 30 Very rare (1%) HP:0002910
20 epicanthus 30 Very rare (1%) HP:0000286
21 pectus excavatum 30 Very rare (1%) HP:0000767
22 talipes equinovarus 30 Very rare (1%) HP:0001762
23 upslanted palpebral fissure 30 Very rare (1%) HP:0000582
24 long philtrum 30 Very rare (1%) HP:0000343
25 ventriculomegaly 30 Very rare (1%) HP:0002119
26 high forehead 30 Very rare (1%) HP:0000348
27 polymicrogyria 30 Very rare (1%) HP:0002126
28 very long chain fatty acid accumulation 30 Very rare (1%) HP:0008167
29 primary adrenal insufficiency 30 Very rare (1%) HP:0008207
30 delayed cranial suture closure 30 Very rare (1%) HP:0000270
31 cholestasis 30 Very rare (1%) HP:0001396
32 cerebellar atrophy 30 Very rare (1%) HP:0001272
33 renal cyst 30 Very rare (1%) HP:0000107
34 visual loss 30 Very rare (1%) HP:0000572
35 hypoplasia of the corpus callosum 30 Very rare (1%) HP:0002079
36 cerebral dysmyelination 30 Very rare (1%) HP:0007266
37 cerebral hypoplasia 30 Very rare (1%) HP:0006872
38 scaphocephaly 30 Very rare (1%) HP:0030799
39 bile duct proliferation 30 Very rare (1%) HP:0001408
40 motor regression 30 Very rare (1%) HP:0033044
41 bilateral tonic-clonic seizure 30 Very rare (1%) HP:0002069
42 calcific stippling 30 Very rare (1%) HP:0002832
43 undetectable electroretinogram 30 Very rare (1%) HP:0000550
44 increased circulating very long-chain fatty acid concentration 30 Very rare (1%) HP:0033643
45 osteopenia 30 HP:0000938
46 delayed skeletal maturation 30 HP:0002750
47 feeding difficulties in infancy 30 HP:0008872
48 decreased muscle mass 30 HP:0003199
49 dolichocephaly 30 HP:0000268
50 polyhydramnios 30 HP:0001561

Symptoms via clinical synopsis from OMIM®:

57 (Updated 24-Oct-2022)
Head And Neck Head:
macrocephaly
large fontanelles
scaphocephaly
delayed closure of the fontanelles

Head And Neck Eyes:
nystagmus
hypertelorism
strabismus
epicanthal folds
upslanting palpebral fissures
more
Muscle Soft Tissue:
decreased muscle mass

Skeletal Feet:
talipes equinovarus
hammertoes

Skeletal:
calcific stippling
delayed bone maturation
generalized osteopenia

Abdomen Gastrointestinal:
poor feeding

Chest External Features:
funnel chest
long, small thorax

Abdomen Liver:
abnormal liver function (26%)
hepatomegaly (43%)
histology shows normal numbers of peroxisomes (84%)
abnormal peroxisomes (53%)
absence of peroxisomes (16%)
more
Neurologic Central Nervous System:
hypotonia, neonatal (> 90%)
seizures (> 90%)
delayed psychomotor development, severe (> 90%)
polymicrogyria (64%)
ventricular dilatation (29%)
more
Endocrine Features:
adrenocortical insufficiency (uncommon)

Head And Neck Face:
frontal bossing
retrognathia
micrognathia
long philtrum
high forehead
more
Head And Neck Nose:
depressed nasal bridge

Head And Neck Ears:
low-set ears
loss of hearing (45%)

Prenatal Manifestations Amniotic Fluid:
polyhydramnios
fetal ascites

Head And Neck Mouth:
high-arched palate

Skeletal Hands:
claw hands

Growth Other:
failure to thrive (44% of patients)

Genitourinary Kidneys:
renal cysts (33%)
adrenal cortex atrophy (42%)

Neurologic Peripheral Nervous System:
delayed peripheral nerve motor conduction velocities (67%)

Laboratory Abnormalities:
increased plasma levels of very long-chain fatty acids (vlcfa)
increased plasma levels of bile acid intermediates
decreased peroxisomal fatty acid beta-oxidation
decreased or absent d-bifunctional protein activity and protein
normal serum plasmalogen

Clinical features from OMIM®:

261515 (Updated 24-Oct-2022)

GenomeRNAi Phenotypes related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

25 (show all 34)
# Description GenomeRNAi Source Accession Score Top Affiliating Genes
1 Increased shRNA abundance (Z-score > 2) GR00366-A-100 10.19 PEX1
2 Increased shRNA abundance (Z-score > 2) GR00366-A-101 10.19 SUOX
3 Increased shRNA abundance (Z-score > 2) GR00366-A-105 10.19 SUOX
4 Increased shRNA abundance (Z-score > 2) GR00366-A-107 10.19 PEX1
5 Increased shRNA abundance (Z-score > 2) GR00366-A-11 10.19 ACOX3
6 Increased shRNA abundance (Z-score > 2) GR00366-A-125 10.19 SUOX
7 Increased shRNA abundance (Z-score > 2) GR00366-A-129 10.19 PEX1
8 Increased shRNA abundance (Z-score > 2) GR00366-A-13 10.19 SUOX
9 Increased shRNA abundance (Z-score > 2) GR00366-A-145 10.19 SUOX
10 Increased shRNA abundance (Z-score > 2) GR00366-A-147 10.19 SUOX
11 Increased shRNA abundance (Z-score > 2) GR00366-A-169 10.19 PEX1 SUOX
12 Increased shRNA abundance (Z-score > 2) GR00366-A-171 10.19 SUOX
13 Increased shRNA abundance (Z-score > 2) GR00366-A-177 10.19 ACOX3
14 Increased shRNA abundance (Z-score > 2) GR00366-A-181 10.19 ACOX3 HADHB PEX1
15 Increased shRNA abundance (Z-score > 2) GR00366-A-2 10.19 SUOX
16 Increased shRNA abundance (Z-score > 2) GR00366-A-204 10.19 SUOX
17 Increased shRNA abundance (Z-score > 2) GR00366-A-205 10.19 SUOX
18 Increased shRNA abundance (Z-score > 2) GR00366-A-207 10.19 PEX1
19 Increased shRNA abundance (Z-score > 2) GR00366-A-209 10.19 SUOX
20 Increased shRNA abundance (Z-score > 2) GR00366-A-21 10.19 SUOX
21 Increased shRNA abundance (Z-score > 2) GR00366-A-26 10.19 HADHB
22 Increased shRNA abundance (Z-score > 2) GR00366-A-30 10.19 ACOX3
23 Increased shRNA abundance (Z-score > 2) GR00366-A-43 10.19 PEX1
24 Increased shRNA abundance (Z-score > 2) GR00366-A-50 10.19 PEX1
25 Increased shRNA abundance (Z-score > 2) GR00366-A-56 10.19 HADHB
26 Increased shRNA abundance (Z-score > 2) GR00366-A-57 10.19 ACOX3
27 Increased shRNA abundance (Z-score > 2) GR00366-A-66 10.19 HADHB
28 Increased shRNA abundance (Z-score > 2) GR00366-A-67 10.19 HADHB
29 Increased shRNA abundance (Z-score > 2) GR00366-A-76 10.19 HADHB
30 Increased shRNA abundance (Z-score > 2) GR00366-A-77 10.19 PEX1
31 Increased shRNA abundance (Z-score > 2) GR00366-A-80 10.19 SUOX
32 no effect GR00402-S-1 10.17 ABCD1 ABCD3 ACOX1 ACOX2 ACOX3 C16orf82
33 no effect GR00402-S-2 10.17 ACOX1 ACOX2 ACOX3 C16orf82 DHRS11 EHHADH
34 Decreased shRNA abundance GR00297-A 9.46 ABCD1 DHRS11 HSD17B4 SUOX

MGI Mouse Phenotypes related to D-Bifunctional Protein Deficiency:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 liver/biliary system MP:0005370 9.23 ABCD3 ACOX1 ACOX2 EHHADH HADHB HSD17B4

Drugs & Therapeutics for D-Bifunctional Protein Deficiency

Drugs for D-Bifunctional Protein Deficiency (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 24)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Rituximab Approved Phase 2 174722-31-7
2
Fludarabine Approved Phase 2 75607-67-9, 21679-14-1 30751 657237
3
Acetylcysteine Approved, Investigational Phase 2 616-91-1 581 12035
4
Celecoxib Approved, Investigational Phase 2 169590-42-5 2662
5
Busulfan Approved, Investigational Phase 2 55-98-1 2478
6
Tocopherol Approved, Investigational Phase 2 1406-66-2
7
Thiotepa Approved, Investigational Phase 2 52-24-4 5453
8
Alemtuzumab Approved, Investigational Phase 2 216503-57-0
9
DL-alpha-Tocopherol Approved, Experimental, Investigational, Nutraceutical, Vet_approved Phase 2 59-02-9, 10191-41-0 2116 14985
10
Lipoic acid Approved, Investigational, Nutraceutical Phase 2 1077-27-6, 1200-22-2 864 445125 6112
11
Tocotrienol Investigational Phase 2 6829-55-6 9929901
12 N-monoacetylcystine Phase 2
13 Vitamins Phase 2
14 Tocotrienols Phase 2
15 Tocopherols Phase 2
16 Antilymphocyte Serum Phase 2
17 Alpha-lipoic Acid Phase 2
18
Ursodeoxycholic acid Approved, Investigational 128-13-2 31401
19
Chenodeoxycholic acid Approved 474-25-9 10133
20 Gastrointestinal Agents
21 Cathartics
22 Bile Acids and Salts
23 Laxatives
24 Cholic Acids

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 MT2013-31: Allogeneic Hematopoietic Cell Transplantation for Inherited Metabolic Disorders and Severe Osteopetrosis Following Conditioning With Busulfan (Therapeutic Drug Monitoring), Fludarabine +/- ATG Recruiting NCT02171104 Phase 2 IMD Preparative Regimen;Osteopetrosis Only Preparative Regimen;Osteopetrosis Haploidentical Only Preparative Regimen;cALD SR-A (Standard-Risk, Regimen A);cALD SR-B (Standard-Risk, Regimen B);cALD HR-D (High-Risk, Regimen C);cALD HR-D (High-Risk, Regimen D)
2 Longitudinal Natural History Study of Patients With Peroxisome Biogenesis Disorders (PBD) Recruiting NCT01668186
3 Study of Bile Acids in Patients With Peroxisomal Disorders Terminated NCT00004442 chenodeoxycholic acid;cholic acid;ursodiol

Search NIH Clinical Center for D-Bifunctional Protein Deficiency

Genetic Tests for D-Bifunctional Protein Deficiency

Genetic tests related to D-Bifunctional Protein Deficiency:

# Genetic test Affiliating Genes
1 Bifunctional Peroxisomal Enzyme Deficiency 28 HSD17B4

Anatomical Context for D-Bifunctional Protein Deficiency

Organs/tissues related to D-Bifunctional Protein Deficiency:

MalaCards : Liver, Kidney, Adrenal Cortex, Cortex, Bone, Retina, Brain
ODiseA: Kidney

Publications for D-Bifunctional Protein Deficiency

Articles related to D-Bifunctional Protein Deficiency:

(show top 50) (show all 131)
# Title Authors PMID Year
1
Mutational spectrum of D-bifunctional protein deficiency and structure-based genotype-phenotype analysis. 53 62 57 5
16385454 2006
2
Specific combination of compound heterozygous mutations in 17β-hydroxysteroid dehydrogenase type 4 (HSD17B4) defines a new subtype of D-bifunctional protein deficiency. 62 57 5
23181892 2012
3
Mutations in the DBP-deficiency protein HSD17B4 cause ovarian dysgenesis, hearing loss, and ataxia of Perrault Syndrome. 62 57 5
20673864 2010
4
D-bifunctional protein deficiency with fetal ascites, polyhydramnios, and contractures of hands and toes. 62 57 5
11743515 2001
5
Peroxisomal D-hydroxyacyl-CoA dehydrogenase deficiency: resolution of the enzyme defect and its molecular basis in bifunctional protein deficiency. 62 57 5
9482850 1998
6
D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency: a newly identified peroxisomal disorder. 62 57 5
9345094 1997
7
Novel subtype of peroxisomal acyl-CoA oxidase deficiency and bifunctional enzyme deficiency with detectable enzyme protein: identification by means of complementation analysis. 62 57 5
8279468 1994
8
Peroxisomal bifunctional enzyme deficiency. 62 57 5
2921319 1989
9
Pseudo-Zellweger syndrome: deficiencies in several peroxisomal oxidative activities. 62 57 5
2868085 1986
10
A novel HPLC-based method to diagnose peroxisomal D-bifunctional protein enoyl-CoA hydratase deficiency. 57 5
12562856 2003
11
Reinvestigation of peroxisomal 3-ketoacyl-CoA thiolase deficiency: identification of the true defect at the level of d-bifunctional protein. 57 5
11992265 2002
12
Peroxisomal bifunctional protein deficiency revisited: resolution of its true enzymatic and molecular basis. 57 5
9915948 1999
13
Human peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. 57 5
2882519 1987
14
Enoyl-CoA hydratase deficiency: identification of a new type of D-bifunctional protein deficiency. 53 62 5
10400999 1999
15
Novel HSD17B4 Variants Cause Progressive Leukodystrophy in Childhood: Case Report and Literature Review. 62 5
34660840 2021
16
Biallelic mutation of HSD17B4 induces middle age-onset spinocerebellar ataxia. 62 5
32042923 2020
17
Unusual Clinical Course and Imaging of D-Bifunctional Protein Deficiency, a Rare Leukodystrophy. 62 5
30396834 2019
18
A homozygous missense variant in HSD17B4 identified in a consanguineous Chinese Han family with type II Perrault syndrome. 62 5
28830375 2017
19
Slowly progressive d-bifunctional protein deficiency with survival to adulthood diagnosed by whole-exome sequencing. 62 5
28017249 2017
20
Heterozygous mutations in HSD17B4 cause juvenile peroxisomal D-bifunctional protein deficiency. 62 5
27790638 2016
21
Peroxisomal D-bifunctional protein deficiency: First case reports from Slovakia. 62 5
25967389 2015
22
D-bifunctional protein deficiency: a cause of neonatal onset seizures and hypotonia. 62 5
25882080 2015
23
Next generation sequencing with copy number variant detection expands the phenotypic spectrum of HSD17B4-deficiency. 62 5
24602372 2014
24
Peroxisomal D-bifunctional protein deficiency: three adults diagnosed by whole-exome sequencing. 62 5
24553428 2014
25
On the molecular basis of D-bifunctional protein deficiency type III. 62 5
23308274 2013
26
Hydratase activities of green fluorescent protein tagged human multifunctional enzyme type 2 hydratase domain and its variants. 62 5
22864515 2012
27
Typical cMRI pattern as diagnostic clue for D-bifunctional protein deficiency without apparent biochemical abnormalities in plasma. 62 57
20949532 2010
28
Clinical and biochemical spectrum of D-bifunctional protein deficiency. 62 57
16278854 2006
29
Molecular analysis of genomic DNA allows rapid, and accurate, prenatal diagnosis of peroxisomal D-bifunctional protein deficiency. 62 5
11810648 2002
30
A case of pseudo-Zellweger syndrome with a possible bifunctional enzyme deficiency but detectable enzyme protein. Comparison of two cases of Zellweger syndrome. 62 57
8147505 1993
31
Bifunctional enzyme deficiency: identification of a new type of peroxisomal disorder in a patient with an impairment in peroxisomal beta-oxidation of unknown aetiology by means of complementation analysis. 62 57
1357231 1992
32
Perrault syndrome with neurological features in a compound heterozygote for two TWNK mutations: overlap of TWNK-related recessive disorders. 5
31455392 2019
33
The many faces of peroxisomal disorders: Lessons from a large Arab cohort. 5
30561787 2019
34
Use of Exome Sequencing for Infants in Intensive Care Units: Ascertainment of Severe Single-Gene Disorders and Effect on Medical Management. 5
28973083 2017
35
Expanding the genotypic spectrum of Perrault syndrome. 5
26970254 2017
36
Mini-Exome Coupled to Read-Depth Based Copy Number Variation Analysis in Patients with Inherited Ataxias. 5
27528516 2016
37
Targeted Next Generation Sequencing in Patients with Inborn Errors of Metabolism. 5
27243974 2016
38
Genetics of primary ovarian insufficiency: new developments and opportunities. 5
26243799 2015
39
Exome sequencing as a diagnostic tool for pediatric-onset ataxia. 5
24108619 2014
40
A clinical evaluation tool for SNP arrays, especially for autosomal recessive conditions in offspring of consanguineous parents. 5
23100014 2013
41
Splicing in action: assessing disease causing sequence changes. 5
16199547 2005
42
Inactivation of the peroxisomal multifunctional protein-2 in mice impedes the degradation of not only 2-methyl-branched fatty acids and bile acid intermediates but also of very long chain fatty acids. 5
10748062 2000
43
Molecular changes in the D-bifunctional protein cDNA sequence in Australasian patients belonging to the bifunctional protein complementation group. 5
11330053 2000
44
Yeast peroxisomal multifunctional enzyme: (3R)-hydroxyacyl-CoA dehydrogenase domains A and B are required for optimal growth on oleic acid. 5
10497229 1999
45
Characterization of the HSD17B4 gene: D-specific multifunctional protein 2/17beta-hydroxysteroid dehydrogenase IV. 5
10419023 1999
46
Prenatal diagnosis of peroxisomal D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein deficiency. 57
10319576 1999
47
Distinction between peroxisomal bifunctional enzyme and acyl-CoA oxidase deficiencies. 57
7668838 1995
48
Bile acid profiles in peroxisomal 3-oxoacyl-coenzyme A thiolase deficiency. 57
2318981 1990
49
A bifunctional protein with deficient enzymic activity: identification of a new peroxisomal disorder using novel methods to measure the peroxisomal beta-oxidation enzyme activities. 57
2122104 1990
50
Neonatal seizures and retardation in a girl with biochemical features of X-linked adrenoleukodystrophy: a possible new peroxisomal disease entity. 57
3386829 1988

Variations for D-Bifunctional Protein Deficiency

ClinVar genetic disease variations for D-Bifunctional Protein Deficiency:

5 (show top 50) (show all 534)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 HSD17B4 NM_000414.4(HSD17B4):c.1212_1261+2del DEL Pathogenic
7653 rs1554065670 GRCh37: 5:118837734-118837785
GRCh38: 5:119502039-119502090
2 HSD17B4 NM_000414.4(HSD17B4):c.974_1209+1del DEL Pathogenic
7654 rs1554065254 GRCh37: 5:118835010-118835246
GRCh38: 5:119499315-119499551
3 HSD17B4 NM_000414.4(HSD17B4):c.317G>C (p.Arg106Pro) SNV Pathogenic
Benign
Benign
7657 rs25640 GRCh37: 5:118811533-118811533
GRCh38: 5:119475838-119475838
4 HSD17B4 NM_000414.4(HSD17B4):c.423_424del (p.Lys142fs) DEL Pathogenic
7659 rs775832137 GRCh37: 5:118813184-118813185
GRCh38: 5:119477489-119477490
5 HSD17B4 NM_000414.4(HSD17B4):c.302+3_302+6del DEL Pathogenic
218138 rs863225438 GRCh37: 5:118811423-118811426
GRCh38: 5:119475728-119475731
6 HSD17B4 NM_000414.4(HSD17B4):c.1984del (p.Ala662fs) DEL Pathogenic
1333681 GRCh37: 5:118867087-118867087
GRCh38: 5:119531392-119531392
7 HSD17B4 NM_000414.4(HSD17B4):c.1993+1G>A SNV Pathogenic
802151 rs1580711803 GRCh37: 5:118867100-118867100
GRCh38: 5:119531405-119531405
8 HSD17B4 GRCh37/hg19 5q23.1(chr5:118811401-118814716) CN LOSS Pathogenic
813314 GRCh37: 5:118811401-118814716
GRCh38:
9 HSD17B4 NM_000414.4(HSD17B4):c.302+3delinsTGTTGTGATTTTTTAGTGAATTGTGTATTTTAGTGATGTGTGTATAATTTTTTTAAAAAGTATATACTTTCCTCCTTTTACCCTATACAACATTGATTT INDEL Pathogenic
1252039 GRCh37: 5:118811425-118811425
GRCh38: 5:119475730-119475730
10 HSD17B4 NM_000414.4(HSD17B4):c.751C>T (p.Arg251Trp) SNV Pathogenic
559068 rs771780974 GRCh37: 5:118829524-118829524
GRCh38: 5:119493829-119493829
11 HSD17B4 NM_000414.4(HSD17B4):c.296dup (p.Asn99fs) DUP Pathogenic
Likely Pathogenic
370669 rs1057516672 GRCh37: 5:118811414-118811415
GRCh38: 5:119475719-119475720
12 HSD17B4 NM_000414.4(HSD17B4):c.67C>T (p.Arg23Ter) SNV Pathogenic
Likely Pathogenic
371607 rs765702241 GRCh37: 5:118792018-118792018
GRCh38: 5:119456323-119456323
13 HSD17B4 NM_000414.4(HSD17B4):c.270del (p.Phe90fs) DEL Pathogenic
Likely Pathogenic
550351 rs1276397342 GRCh37: 5:118810142-118810142
GRCh38: 5:119474447-119474447
14 HSD17B4 NM_000414.4(HSD17B4):c.590_597dup (p.Met200fs) DUP Pathogenic
1404290 GRCh37: 5:118814680-118814681
GRCh38: 5:119478985-119478986
15 HSD17B4 NM_000414.4(HSD17B4):c.682G>T (p.Glu228Ter) SNV Pathogenic
1357638 GRCh37: 5:118824946-118824946
GRCh38: 5:119489251-119489251
16 HSD17B4 NM_000414.4(HSD17B4):c.439del (p.Ile147fs) DEL Pathogenic
1371276 GRCh37: 5:118814533-118814533
GRCh38: 5:119478838-119478838
17 HSD17B4 NM_000414.4(HSD17B4):c.1235_1236del (p.Glu412fs) MICROSAT Pathogenic
1353412 GRCh37: 5:118837759-118837760
GRCh38: 5:119502064-119502065
18 HSD17B4 NM_000414.4(HSD17B4):c.1480_1481insGA (p.Thr494fs) INSERT Pathogenic
1423489 GRCh37: 5:118850717-118850718
GRCh38: 5:119515022-119515023
19 HSD17B4 NM_000414.4(HSD17B4):c.1708G>T (p.Gly570Ter) SNV Pathogenic
1416308 GRCh37: 5:118862855-118862855
GRCh38: 5:119527160-119527160
20 HSD17B4 NM_000414.4(HSD17B4):c.698dup (p.Asn233fs) DUP Pathogenic
1460126 GRCh37: 5:118824960-118824961
GRCh38: 5:119489265-119489266
21 HSD17B4 NM_000414.4(HSD17B4):c.728G>A (p.Trp243Ter) SNV Pathogenic
1459060 GRCh37: 5:118827808-118827808
GRCh38: 5:119492113-119492113
22 HSD17B4 NM_000414.4(HSD17B4):c.740T>G (p.Leu247Ter) SNV Pathogenic
1454962 GRCh37: 5:118829513-118829513
GRCh38: 5:119493818-119493818
23 HSD17B4 NM_000414.4(HSD17B4):c.1233dup (p.Glu412fs) DUP Pathogenic
1441941 GRCh37: 5:118837758-118837759
GRCh38: 5:119502063-119502064
24 HSD17B4 NM_000414.4(HSD17B4):c.605dup (p.Thr203fs) DUP Pathogenic
1458501 GRCh37: 5:118814698-118814699
GRCh38: 5:119479003-119479004
25 HSD17B4 NM_000414.4(HSD17B4):c.657del (p.Pro220fs) DEL Pathogenic
1453246 GRCh37: 5:118824921-118824921
GRCh38: 5:119489226-119489226
26 HSD17B4 NM_000414.4(HSD17B4):c.1954_1970del (p.Trp652fs) DEL Pathogenic
1448621 GRCh37: 5:118867059-118867075
GRCh38: 5:119531364-119531380
27 HSD17B4 NM_000414.4(HSD17B4):c.1230C>G (p.Tyr410Ter) SNV Pathogenic
1452066 GRCh37: 5:118837756-118837756
GRCh38: 5:119502061-119502061
28 HSD17B4 NM_000414.4(HSD17B4):c.1352del (p.Lys451fs) DEL Pathogenic
854726 rs1751933402 GRCh37: 5:118844853-118844853
GRCh38: 5:119509158-119509158
29 HSD17B4 NM_000414.4(HSD17B4):c.1147C>T (p.Gln383Ter) SNV Pathogenic
861128 rs1750958514 GRCh37: 5:118835186-118835186
GRCh38: 5:119499491-119499491
30 HSD17B4 NM_000414.4(HSD17B4):c.1424C>G (p.Ser475Ter) SNV Pathogenic
939009 rs1751944228 GRCh37: 5:118844926-118844926
GRCh38: 5:119509231-119509231
31 HSD17B4 NM_000414.4(HSD17B4):c.1659_1660dup (p.Ser554fs) MICROSAT Pathogenic
949620 rs1753560558 GRCh37: 5:118861693-118861694
GRCh38: 5:119525998-119525999
32 HSD17B4 NM_000414.4(HSD17B4):c.911C>G (p.Ser304Ter) SNV Pathogenic
1070670 GRCh37: 5:118832280-118832280
GRCh38: 5:119496585-119496585
33 HSD17B4 NM_000414.4(HSD17B4):c.1499del (p.Asn500fs) DEL Pathogenic
1071247 GRCh37: 5:118850736-118850736
GRCh38: 5:119515041-119515041
34 HSD17B4 NM_000414.4(HSD17B4):c.1921G>T (p.Glu641Ter) SNV Pathogenic
1071457 GRCh37: 5:118867027-118867027
GRCh38: 5:119531332-119531332
35 HSD17B4 NM_000414.4(HSD17B4):c.1748_1749del (p.Arg583fs) DEL Pathogenic
Likely Pathogenic
554583 rs1554068426 GRCh37: 5:118862894-118862895
GRCh38: 5:119527199-119527200
36 HSD17B4 NM_000414.4(HSD17B4):c.1951G>T (p.Glu651Ter) SNV Pathogenic
1074898 GRCh37: 5:118867057-118867057
GRCh38: 5:119531362-119531362
37 HSD17B4 NM_000414.4(HSD17B4):c.1578del (p.Phe526fs) DEL Pathogenic
582190 rs1561485663 GRCh37: 5:118861613-118861613
GRCh38: 5:119525918-119525918
38 HSD17B4 NC_000005.9:g.(?_118788261)_(118807405_?)del DEL Pathogenic
1071509 GRCh37: 5:118788261-118807405
GRCh38:
39 HSD17B4 NC_000005.9:g.(?_118865579)_(118867109_?)del DEL Pathogenic
1075507 GRCh37: 5:118865579-118867109
GRCh38:
40 HSD17B4 NM_000414.4(HSD17B4):c.1210-1G>A SNV Pathogenic
Likely Pathogenic
551541 rs1554065671 GRCh37: 5:118837735-118837735
GRCh38: 5:119502040-119502040
41 HSD17B4 NM_000414.4(HSD17B4):c.1369A>G (p.Asn457Asp) SNV Pathogenic
Pathogenic
Pathogenic/Likely Pathogenic
Likely Pathogenic
Likely Pathogenic
371413 rs137853097 GRCh37: 5:118844871-118844871
GRCh38: 5:119509176-119509176
42 HSD17B4 NM_000414.4(HSD17B4):c.1630_1633dup (p.Leu545fs) MICROSAT Pathogenic
Likely Pathogenic
371505 rs1057517323 GRCh37: 5:118861665-118861666
GRCh38: 5:119525970-119525971
43 HSD17B4 NM_000414.4(HSD17B4):c.742C>T (p.Arg248Cys) SNV Pathogenic
Pathogenic/Likely Pathogenic
371366 rs969485098 GRCh37: 5:118829515-118829515
GRCh38: 5:119493820-119493820
44 HSD17B4 NM_000414.4(HSD17B4):c.868+1del DEL Pathogenic
Pathogenic/Likely Pathogenic
632857 rs749532705 GRCh37: 5:118829641-118829641
GRCh38: 5:119493946-119493946
45 HSD17B4 NM_000414.4(HSD17B4):c.1717_1718del (p.Leu573fs) MICROSAT Pathogenic
Likely Pathogenic
371008 rs1057516936 GRCh37: 5:118862862-118862863
GRCh38: 5:119527167-119527168
46 HSD17B4 NM_000414.4(HSD17B4):c.936_937del (p.His312_Thr313insTer) DEL Pathogenic
Pathogenic
Pathogenic
504023 rs758055753 GRCh37: 5:118832304-118832305
GRCh38: 5:119496609-119496610
47 HSD17B4 NM_000414.4(HSD17B4):c.1537C>A (p.Pro513Thr) SNV Pathogenic
Uncertain Significance
1074454 GRCh37: 5:118860944-118860944
GRCh38: 5:119525249-119525249
48 HSD17B4 NM_000414.4(HSD17B4):c.421C>T (p.Gln141Ter) SNV Pathogenic
1075802 GRCh37: 5:118813183-118813183
GRCh38: 5:119477488-119477488
49 HSD17B4 NM_000414.4(HSD17B4):c.394C>T (p.Arg132Trp) SNV Pathogenic
Pathogenic/Likely Pathogenic
554818 rs773305477 GRCh37: 5:118813156-118813156
GRCh38: 5:119477461-119477461
50 HSD17B4 NM_000414.4(HSD17B4):c.1516C>T (p.Arg506Cys) SNV Pathogenic
Pathogenic
Likely Pathogenic
495866 rs766199971 GRCh37: 5:118860923-118860923
GRCh38: 5:119525228-119525228

UniProtKB/Swiss-Prot genetic disease variations for D-Bifunctional Protein Deficiency:

73
# Symbol AA change Variation ID SNP ID
1 HSD17B4 p.Gly16Ser VAR_037576 rs137853096
2 HSD17B4 p.Arg106Pro VAR_065906 rs25640
3 HSD17B4 p.Asn457Tyr VAR_065908 rs137853097

Expression for D-Bifunctional Protein Deficiency

Search GEO for disease gene expression data for D-Bifunctional Protein Deficiency.

Pathways for D-Bifunctional Protein Deficiency

Pathways related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
13.52 SUOX SCP2 HSD17B4 HADHB HADH ELOVL1
2
Show member pathways
12.36 SCP2 HSD17B4 HADHB HADH ELOVL1 EHHADH
3
Show member pathways
11.9 SCP2 PEX6 PEX1 HSD17B4 EHHADH ACOX3
4
Show member pathways
11.86 SCP2 HSD17B4 ACOX2
5
Show member pathways
11.59 SCP2 EHHADH ACOX3 ACOX2 ACOX1
6
Show member pathways
11.53 LARS2 HADH EHHADH
7
Show member pathways
11.48 ABCD1 ACOX1 EHHADH ELOVL1 HSD17B4 SCP2
8 10.85 SCP2 EHHADH
9
Show member pathways
10.68 HADHB EHHADH

GO Terms for D-Bifunctional Protein Deficiency

Cellular components related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 peroxisomal membrane GO:0005778 9.93 PEX6 PEX1 HSD17B4 ACOX1 ABCD3 ABCD1
2 peroxisomal matrix GO:0005782 9.8 ABCD3 ACOX1 ACOX2 ACOX3 EHHADH HSD17B4
3 peroxisome GO:0005777 9.62 SCP2 PEX6 PEX1 HSD17B4 EHHADH ACOX3

Biological processes related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

(show all 17)
# Name GO ID Score Top Affiliating Genes
1 lipid metabolic process GO:0006629 10.06 ACOX1 ACOX2 ACOX3 DHRS11 EHHADH ELOVL1
2 lipid homeostasis GO:0055088 10.01 ACOX3 ACOX2 ACOX1
3 steroid biosynthetic process GO:0006694 10 SCP2D1 SCP2 DHRS11
4 peroxisome organization GO:0007031 9.97 PEX6 PEX1 ABCD3 ABCD1
5 very long-chain fatty acid metabolic process GO:0000038 9.96 HSD17B4 ACOX2 ACOX1 ABCD3 ABCD1
6 alpha-linolenic acid metabolic process GO:0036109 9.88 SCP2 ELOVL1 ABCD1
7 protein import into peroxisome matrix GO:0016558 9.87 PEX6 PEX1
8 protein targeting to peroxisome GO:0006625 9.85 PEX6 PEX1
9 very long-chain fatty acid catabolic process GO:0042760 9.81 ABCD3 ABCD1
10 long-chain fatty acid import into peroxisome GO:0015910 9.8 ABCD1 ABCD3
11 fatty acid metabolic process GO:0006631 9.76 HSD17B4 HADHB HADH ELOVL1 EHHADH ACOX3
12 fatty acid elongation GO:0030497 9.73 ELOVL1 ABCD1
13 positive regulation of intracellular cholesterol transport GO:0032385 9.73 SCP2D1 SCP2
14 fatty acid beta-oxidation using acyl-CoA oxidase GO:0033540 9.65 ACOX1 ACOX2 ACOX3 EHHADH SCP2
15 fatty acid beta-oxidation GO:0006635 9.55 SCP2 HSD17B4 HADHB HADH EHHADH ACOX3
16 protein unfolding GO:0043335 9.48 PEX1 PEX6
17 protein import into peroxisome matrix, receptor recycling GO:0016562 9.46 PEX6 PEX1

Molecular functions related to D-Bifunctional Protein Deficiency according to GeneCards Suite gene sharing:

(show all 19)
# Name GO ID Score Top Affiliating Genes
1 flavin adenine dinucleotide binding GO:0050660 10.02 ACOX1 ACOX2 ACOX3
2 FAD binding GO:0071949 9.97 ACOX3 ACOX2 ACOX1
3 fatty acid binding GO:0005504 9.93 ACOX1 ACOX2 ACOX3
4 NAD+ binding GO:0070403 9.88 HADH EHHADH
5 long-chain fatty acid transporter activity GO:0005324 9.88 ABCD3 ABCD1
6 acyl-CoA hydrolase activity GO:0047617 9.87 ABCD3 ABCD1
7 17-beta-hydroxysteroid dehydrogenase (NAD+) activity GO:0044594 9.86 HSD17B4 DHRS11
8 acetyl-CoA C-acyltransferase activity GO:0003988 9.78 SCP2 HADHB
9 palmitoyl-CoA oxidase activity GO:0016401 9.73 ACOX2 ACOX1
10 enoyl-CoA hydratase activity GO:0004300 9.73 EHHADH HADHB HSD17B4
11 acetyl-CoA C-myristoyltransferase activity GO:0050633 9.71 SCP2 HADHB
12 long-chain-enoyl-CoA hydratase activity GO:0016508 9.67 HSD17B4 EHHADH
13 acyl-CoA oxidase activity GO:0003997 9.63 ACOX3 ACOX2 ACOX1
14 oxidoreductase activity GO:0016491 9.56 SUOX HSD17B4 HADH EHHADH DHRS11 ACOX3
15 protein transporter activity GO:0140318 9.54 PEX6 PEX1
16 ubiquitin-dependent protein binding GO:0140036 9.52 PEX6 PEX1
17 acyltransferase activity, transferring groups other than amino-acyl groups GO:0016747 9.51 SCP2 HADHB
18 oxidoreductase activity, acting on the CH-CH group of donors GO:0016627 9.5 ACOX3 ACOX2 ACOX1
19 3-hydroxyacyl-CoA dehydrogenase activity GO:0003857 9.23 HSD17B4 HADHB HADH EHHADH

Sources for D-Bifunctional Protein Deficiency

2 CDC
6 CNVD
8 Cosmic
9 dbSNP
10 DGIdb
16 EFO
17 ExPASy
18 FMA
19 GARD
27 GO
28 GTR
29 HMDB
30 HPO
31 ICD10
32 ICD10 via Orphanet
33 ICD11
34 ICD9CM
35 IUPHAR
36 LifeMap
38 LOVD
40 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
52 NINDS
53 Novoseek
55 ODiseA
56 OMIM via Orphanet
57 OMIM® (Updated 24-Oct-2022)
61 PubChem
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 Tocris
71 UMLS
72 UMLS via Orphanet
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