Pyruvate dehydrogenase phosphatase deficiency

General Information (adopted from Orphanet):

Synonyms, Signs: PDHPD
PDH phosphatase deficiency
Lactic acidemia with pyruvate dehydrogenase phosphatase deficiency
Number of Symptoms 30
OrphanetNr: 79246
OMIM Id: 608782
ICD-10: E74.4
UMLs:
MeSH:
MedDRA:
Snomed:

Prevalence, inheritance and age of onset:

Prevalence: No data available.
Inheritance: Autosomal recessive
[Orphanet]
Age of onset: Neonatal
Infancy
19184109 [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 phosphatase (PDP) is an enzyme which regulates the activity of the pyruvate dehydrogenase complex (PDHc). There exist two isoforms of PDP, PDP1 (= PDH, PDP, PDPC, PPM2A, PPM2C) and PDP2 (= PDPC2, PPM2B, PPM2C2), which results in severe exercise intolerance and mild developmental delay in patients (PMID:16574315). PDP1 is largely regulated by changes in calcium concentration, whereas PDP2 appears not to be regulated by calcium and is more involved with long-term regulation (PMID:19184109).

Symptom Information: Sort by abundance 

1
 (HPO:0004885) Episodic respiratory distress 19184109 IBIS 2 / 7739
2
 (HPO:0002151) Increased serum lactate 172850 IBIS 92 / 7739
3
 (HPO:0003128) Lactic acidosis 19184109 IBIS 116 / 7739
4
 (HPO:0001942) Metabolic acidosis 172850 IBIS 81 / 7739
5
 (HPO:0001943) Hypoglycemia 19184109 IBIS 131 / 7739
6
 (HPO:0003542) Increased serum pyruvate 172850 IBIS 18 / 7739
7
 (HPO:0003348) Hyperalaninemia 19184109 IBIS 19 / 7739
8
 (HPO:0003112) Abnormality of serum amino acid levels 19184109 IBIS 2 / 7739
9
 (HPO:0008358) Hyperprolinemia 19184109 IBIS 5 / 7739
10
 (HPO:0011923) Decreased activity of mitochondrial complex I 19184109 IBIS 35 / 7739
11
 (HPO:0011924) Decreased activity of mitochondrial complex III 19184109 IBIS 22 / 7739
12
 (HPO:0002928) Decreased activity of the pyruvate dehydrogenase complex 19184109 IBIS 10 / 7739
13
 (HPO:0002181) Cerebral edema 19184109 IBIS 19 / 7739
14
 (HPO:0001992) Organic aciduria 19184109 IBIS 28 / 7739
15
 (HPO:0001252) Muscular hypotonia 19184109 IBIS 990 / 7739
16
 (HPO:0008947) Infantile muscular hypotonia 19184109 IBIS 482 / 7739
17
 (HPO:0003546) Exercise intolerance 16574315 IBIS 62 / 7739
18
 (HPO:0001263) Global developmental delay 16574315 IBIS 853 / 7739
19
 (HPO:0000737) Irritability 172850 IBIS 93 / 7739
20
 (HPO:0001254) Lethargy 172850 IBIS 104 / 7739
21
 (HPO:0004372) Reduced consciousness/confusion 172850 IBIS 73 / 7739
22
 (HPO:0001250) Seizures 19184109 IBIS 1245 / 7739
23
 (HPO:0012402) Increased urine alpha-ketoglutarate concentration 19184109 IBIS 3 / 7739
24
 (HPO:0002789) Tachypnea 19184109 IBIS 48 / 7739
25
 (HPO:0001522) Death in infancy 172850 IBIS 275 / 7739
26
 (HPO:0007042) Focal white matter lesions 19184109 IBIS 7 / 7739
27
 (HPO:0002180) Neurodegeneration 19184109 IBIS 31 / 7739
28
 (MedDRA:10017349) Free fatty acids increased 172850 IBIS 1 / 7739
29
 (MedDRA:10023499) Kussmaul respiration 172850 IBIS 1 / 7739
30
 (OMIM) Decreased activity of the PDH phosphatase 19184109 IBIS 1 / 7739

Associated genes:

PDP1;

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Clinical Description OMIM Robinson and Sherwood (1975) reported a male infant who presented on the first day of life with lactic acidosis and died at age 6 months. Activity of the pyruvate dehydrogenase complex in tissue homogenates preincubated with ATP was ...
Molecular genetics OMIM In 2 brothers, born of consanguineous parents, with pyruvate dehydrogenase phosphatase deficiency, Maj et al. (2005) identified a 3-bp deletion in the PDP1 gene, resulting in loss of leu213 (605993.0001). The activity of the PDHc could be restored ...