Bifunctional enzyme deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: DBP DEFICIENCY
PBFE DEFICIENCY
17-&#64
BETA-HYDROXYSTEROID DEHYDROGENASE IV DEFICIENCY
PEROXISOMAL BIFUNCTIONAL ENZYME DEFICIENCY
Number of Symptoms 86
OrphanetNr: 300
OMIM Id: 261515
ICD-10: E71.3
UMLs: C0342870
MeSH: C536663
MedDRA:
Snomed: 238068007

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive inheritance
[Omim]
Age of onset: Infantile onset
[Omim]

Disease classification (adopted from Orphanet):

Parent Diseases: Peroxisomal beta-oxidation disorder
 -Rare genetic disease

Symptom Information: Sort by abundance 

1
 (HPO:0000107) Renal cyst 126 / 7739
2
 (HPO:0001999) Abnormal facial shape 169 / 7739
3
 (HPO:0002007) Frontal bossing 366 / 7739
4
 (HPO:0000270) Delayed cranial suture closure 33 / 7739
5
 (HPO:0000278) Retrognathia 100 / 7739
6
 (HPO:0000319) Smooth philtrum 72 / 7739
7
 (HPO:0000348) High forehead 157 / 7739
8
 (HPO:0000271) Abnormality of the face 108 / 7739
9
 (HPO:0005280) Depressed nasal bridge 381 / 7739
10
 (HPO:0000239) Large fontanelles 135 / 7739
11
 (HPO:0000347) Micrognathia 426 / 7739
12
 (HPO:0000286) Epicanthus 371 / 7739
13
 (HPO:0000256) Macrocephaly 298 / 7739
14
 (HPO:0000268) Dolichocephaly 144 / 7739
15
 (HPO:0000343) Long philtrum 262 / 7739
16
 (HPO:0000582) Upslanted palpebral fissure 185 / 7739
17
 (HPO:0000316) Hypertelorism 644 / 7739
18
 (HPO:0000218) High palate 356 / 7739
19
 (HPO:0000639) Nystagmus 555 / 7739
20
 (HPO:0000505) Visual impairment 297 / 7739
21
 (HPO:0000550) Undetectable electroretinogram 25 / 7739
22
 (HPO:0000572) Visual loss 272 / 7739
23
 (HPO:0000618) Blindness 124 / 7739
24
 (HPO:0000486) Strabismus 576 / 7739
25
 (HPO:0000369) Low-set ears 372 / 7739
26
 (HPO:0000762) Decreased nerve conduction velocity 67% [HPO:probinson] 36 / 7739
27
 (HPO:0001250) Seizures 1245 / 7739
28
 (HPO:0001327) Photomyoclonic seizures 125 / 7739
29
 (HPO:0001263) Global developmental delay 853 / 7739
30
 (HPO:0008207) Primary adrenal insufficiency 26 / 7739
31
 (HPO:0011735) Adrenocorticotropin deficient adrenal insufficiency 3 / 7739
32
 (HPO:0008182) Adrenocortical hypoplasia 4 / 7739
33
 (HPO:0000835) Adrenal hypoplasia 23 / 7739
34
 (HPO:0000846) Adrenal insufficiency 24 / 7739
35
 (HPO:0002832) Calcific stippling 5 / 7739
36
 (HPO:0000938) Osteopenia 138 / 7739
37
 (HPO:0005257) Thoracic hypoplasia 79 / 7739
38
 (HPO:0001765) Hammertoe 63 / 7739
39
 (HPO:0001762) Talipes equinovarus 309 / 7739
40
 (HPO:0000767) Pectus excavatum 244 / 7739
41
 (HPO:0002750) Delayed skeletal maturation 250 / 7739
42
 (HPO:0001171) Split hand 72 / 7739
43
 (HPO:0001561) Polyhydramnios 191 / 7739
44
 (HPO:0001791) Fetal ascites 4 / 7739
45
 (HPO:0002240) Hepatomegaly 467 / 7739
46
 (HPO:0002611) Cholestatic liver disease 19 / 7739
47
 (HPO:0008872) Feeding difficulties in infancy 153 / 7739
48
 (HPO:0002910) Elevated hepatic transaminases 158 / 7739
49
 (HPO:0001396) Cholestasis 136 / 7739
50
 (HPO:0011968) Feeding difficulties 240 / 7739
51
 (HPO:0001408) Bile duct proliferation 22 / 7739
52
 (HPO:0001397) Hepatic steatosis 75 / 7739
53
 (HPO:0001508) Failure to thrive 454 / 7739
54
 (HPO:0001510) Growth delay 295 / 7739
55
 (HPO:0003281) Increased serum ferritin 32 / 7739
56
 (HPO:0001319) Neonatal hypotonia 101 / 7739
57
 (HPO:0003199) Decreased muscle mass 27 / 7739
58
 (OMIM) Increased plasma levels of very long-chain fatty acids (VLCFA) 2 / 7739
59
 (OMIM) Absence of peroxisomes (16%) 1 / 7739
60
 (OMIM) Adrenal cortex atrophy (42%) 1 / 7739
61
 (HPO:0002171) Gliosis 48 / 7739
62
 (OMIM) Long, small thorax 1 / 7739
63
 (OMIM) Normal serum plasmalogen 2 / 7739
64
 (OMIM) Failure to fixate on objects 1 / 7739
65
 (HPO:0007266) Cerebral dysmyelination 13 / 7739
66
 (HPO:0002079) Hypoplasia of the corpus callosum 161 / 7739
67
 (HPO:0006872) Cerebral hypoplasia 45% [HPO:probinson] 7 / 7739
68
 (OMIM) Delayed peripheral nerve motor conduction velocities (67%) 1 / 7739
69
 (HPO:0007360) Aplasia/Hypoplasia of the cerebellum 10 / 7739
70
 (OMIM) Loss of hearing (45%) 1 / 7739
71
 (HPO:0002126) Polymicrogyria 64 / 7739
72
 (OMIM) Histology shows normal numbers of peroxisomes (84%) 1 / 7739
73
 (HPO:0000007) Autosomal recessive inheritance 2538 / 7739
74
 (HPO:0007058) Generalized cerebral atrophy/hypoplasia 1 / 7739
75
 (OMIM) Abnormal peroxisomes (53%) 2 / 7739
76
 (OMIM) Heterotopic neurons in the white matter (36%) 1 / 7739
77
 (HPO:0003593) Infantile onset 249 / 7739
78
 (OMIM) Increased plasma levels of bile acid intermediates 1 / 7739
79
 (HPO:0002119) Ventriculomegaly 253 / 7739
80
 (HPO:0002539) Cortical dysplasia 19 / 7739
81
 (OMIM) Delayed psychomotor development, severe 14 / 7739
82
 (MedDRA:10016642) Fibrosis 9 / 7739
83
 (OMIM) Hypoplastic/atrophic corpus callosum (55%) 1 / 7739
84
 (OMIM) Decreased or absent D-bifunctional protein activity and protein 2 / 7739
85
 (HPO:0007371) Corpus callosum atrophy 14 / 7739
86
 (OMIM) Decreased peroxisomal fatty acid beta-oxidation 1 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) 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 ...
Diagnosis OMIM The diagnosis of DBP deficiency is commonly made based on the accumulation of very long chain fatty acids (VLCFA), dihydroxy- and trihydroxycholestanoic acid (DHCA and THCA), and pristanic and phytanic acid in plasma. However, some patients with residual ...
Clinical Description OMIM Watkins et al. (1989) reported a black male infant with neonatal hypotonia and macrocephaly who developed seizures and required ventilatory support for the first 4 days of life. By 6 weeks of age, he had made no developmental ...
Molecular genetics OMIM In 2 Japanese patients reported by Suzuki et al. (1994) as having L-bifunctional protein deficiency, Suzuki et al. (1997) identified 2 different homozygous deletions in the HSD17B4 gene (601860.0001; 601860.0002), confirming D-bifunctional protein deficiency.

In 9 ...
Population genetics OMIM DBP deficiency has an estimated prevalence of 1 in 100,000 (Ferdinandusse et al., 2006).