Pyruvate dehydrogenase E3-binding protein deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: PDHXD
Lactic acidemia due to defect in lipoyl-containing component X of the pyruvate dehydrogenase complex
Pyruvate dehydrogenase complex component E3 deficiency
Pyruvate dehydrogenase protein X component deficiency
Lipoamide dehydrogenase deficiency
Diaphorase deficiency
2-oxoglutarate complex deficiency
Glycine cleavage system L protein deficiency
Branched chain alpha-ketoacid dehydrogenase complex deficiency
Dihydrolipoyl dehydrogenase deficiency
Number of Symptoms 61
OrphanetNr: 255182
OMIM Id: 245349
ICD-10: E74.4
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
16904023 [IBIS]
Age of onset: Neonatal
Infancy
Childhood
16904023 [IBIS]

Disease classification (adopted from Orphanet):

Parent Diseases: Pyruvate dehydrogenase deficiency
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare neurologic disease

Comment:

Pyruvate dehydrogenase deficiency is one of the genetic defects of mitochondrial energy metabolism. Clinical features are heterogeneous, ranging from fatal lactic acidosis in the newborn period to chronic neurodegenerative abnormalities. Most cases have mutations in the gene for the E1alpha subunit of the pyruvate dehydrogenase complex. Primary defects of the E3 binding protein component of the pyruvate dehydrogenase complex (PDHX = DLDBP, E3BP, OPDX, PDX1, proX) are uncommon (PMID:22766002).

Symptom Information: Sort by abundance 

1
 (HPO:0011471) Gastrostomy tube feeding in infancy 16904023 IBIS 3 / 7739
2
 (HPO:0000316) Hypertelorism 9501264 IBIS 644 / 7739
3
 (HPO:0000648) Optic atrophy 22766002 IBIS 238 / 7739
4
 (HPO:0000496) Abnormality of eye movement 12557299 IBIS 79 / 7739
5
 (HPO:0000505) Visual impairment Occasional [IBIS] 21% (n=19) 16904023 IBIS 297 / 7739
6
 (HPO:0002090) Pneumonia 16904023 IBIS 59 / 7739
7
 (HPO:0003128) Lactic acidosis Very frequent [IBIS] 100% (n=19) 16904023 IBIS 116 / 7739
8
 (HPO:0001942) Metabolic acidosis 15303005 IBIS 81 / 7739
9
 (HPO:0001508) Failure to thrive 9501264 IBIS 454 / 7739
10
 (HPO:0001943) Hypoglycemia 16904023 IBIS 131 / 7739
11
 (HPO:0003542) Increased serum pyruvate 22766002 IBIS 18 / 7739
12
 (HPO:0003348) Hyperalaninemia 22766002 IBIS 19 / 7739
13
 (HPO:0002119) Ventriculomegaly 22766002 IBIS 253 / 7739
14
 (HPO:0001662) Bradycardia 16904023 IBIS 41 / 7739
15
 (HPO:0004755) Supraventricular tachycardia 16904023 IBIS 20 / 7739
16
 (HPO:0002928) Decreased activity of the pyruvate dehydrogenase complex 22766002 IBIS 10 / 7739
17
 (HPO:0001252) Muscular hypotonia Very frequent [IBIS] 100% (n=19) 16904023 IBIS 990 / 7739
18
 (HPO:0001319) Neonatal hypotonia 16904023 IBIS 101 / 7739
19
 (HPO:0002490) Increased CSF lactate 16904023 IBIS 28 / 7739
20
 (HPO:0007109) Periventricular cysts 16904023 IBIS 4 / 7739
21
 (HPO:0006970) Periventricular leukomalacia 22766002 IBIS 7 / 7739
22
 (HPO:0001251) Ataxia Occasional [IBIS] 11% (n=19) 16904023 IBIS 413 / 7739
23
 (HPO:0007010) Poor fine motor coordination 2112155 IBIS 4 / 7739
24
 (HPO:0007015) Poor gross motor coordination 2112155 IBIS 2 / 7739
25
 (HPO:0007256) Abnormal pyramidal signs 22766002 IBIS 116 / 7739
26
 (HPO:0001348) Brisk reflexes 16904023 IBIS 15 / 7739
27
 (HPO:0001276) Hypertonia 22766002 IBIS 317 / 7739
28
 (HPO:0002313) Spastic paraparesis 22766002 IBIS 33 / 7739
29
 (HPO:0001264) Spastic diplegia 22766002 IBIS 24 / 7739
30
 (HPO:0002445) Tetraplegia 22766002 IBIS 26 / 7739
31
 (HPO:0001332) Dystonia 22766002 IBIS 197 / 7739
32
 (HPO:0001263) Global developmental delay Very frequent [IBIS] 100% (n=19) 16904023 IBIS 853 / 7739
33
 (HPO:0000737) Irritability 16904023 IBIS 93 / 7739
34
 (HPO:0012171) Stereotypical hand wringing 16904023 IBIS 1 / 7739
35
 (HPO:0000750) Delayed speech and language development 16904023 IBIS 197 / 7739
36
 (HPO:0002317) Unsteady gait 15303005 IBIS 45 / 7739
37
 (HPO:0002353) EEG abnormality 16904023 IBIS 188 / 7739
38
 (HPO:0002521) Hypsarrhythmia 16904023 IBIS 43 / 7739
39
 (HPO:0001250) Seizures Occasional [IBIS] 21% (n=19) 16904023 IBIS 1245 / 7739
40
 (HPO:0012469) Infantile spasms 16904023 IBIS 18 / 7739
41
 (MedDRA:10054859) Myoclonic epilepsy 22766002 IBIS 7 / 7739
42
 (HPO:0000243) Trigonocephaly 9501264 IBIS 40 / 7739
43
 (HPO:0000252) Microcephaly 15303005 IBIS 832 / 7739
44
 (HPO:0005487) Prominent metopic ridge 9501264 IBIS 28 / 7739
45
 (HPO:0000767) Pectus excavatum 9501264 IBIS 244 / 7739
46
 (HPO:0001274) Agenesis of corpus callosum Frequent [IBIS] 42% (n=19) 16904023 IBIS 142 / 7739
47
 (HPO:0005249) Functional intestinal obstruction 16904023 IBIS 3 / 7739
48
 (HPO:0000218) High palate 9501264 IBIS 356 / 7739
49
 (HPO:0000286) Epicanthus 9501264 IBIS 371 / 7739
50
 (HPO:0002104) Apnea 16904023 IBIS 106 / 7739
51
 (HPO:0002789) Tachypnea 16904023 IBIS 48 / 7739
52
 (HPO:0002790) Neonatal breathing dysregulation 16904023 IBIS 7 / 7739
53
 (HPO:0002120) Cerebral cortical atrophy 16904023 IBIS 187 / 7739
54
 (HPO:0012762) Cerebral white matter atrophy 16904023 IBIS 3 / 7739
55
 (HPO:0003819) Death in childhood 16904023 IBIS 42 / 7739
56
 (HPO:0001522) Death in infancy 16904023 IBIS 275 / 7739
57
 (HPO:0012448) Delayed myelination 16904023 IBIS 51 / 7739
58
 (HPO:0007183) Focal T2 hyperintense basal ganglia lesion 16904023 IBIS 6 / 7739
59
 (HPO:0002416) Subependymal cysts 16904023 IBIS 6 / 7739
60
 (HPO:0012766) Widened cerebral subarachnoid space 16904023 IBIS 1 / 7739
61
 (OMIM) Pyramidal hypertonia 22766002 IBIS 1 / 7739

Associated genes:

PDHX;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Diagnosis OMIM - Prenatal Diagnosis

Rouillac et al. (1999) described the results of the first prenatal diagnosis based on the PDX1 gene. The heterozygous mother of an affected child reported by Geoffroy et al. (1996) in whom a ...
Clinical Description OMIM Robinson et al. (1990) described 2 patients who had decreased activity of the pyruvate dehydrogenase (PDH) complex without observable reduction in the activities of enzymes E1 (300502/179060), E2 (608770), or E3 (238331). Western blot analysis showed that 1 ...
Molecular genetics OMIM In 4 patients with neonatal lactic acidemia and component X deficiency, Aral et al. (1997) identified 2 different homozygous mutations in the PDHX gene (608769.0001 and 608769.0002). One other patient had no PDHX mRNA expression.

In ...