Pyruvate Dehydrogenase E1-Alpha Deficiency

Pyruvate dehydrogenase complex (PDHc) deficiency is an X-linked inborn error of mitochondrial energy metabolism. Defects in the PDH complex are an important cause of primary lactic acidosis. The phenotype of patients with a PDH complex deficiency include an early neonatal presentation with severe lactic acidosis and early death, a progressive disease with mental retardation and neurological complications, or intermittent ataxia. Recurrent acute proximal muscle weakness of upper and lower extremities has also been reported as the presenting feature in one affected individual. Dysmorphic features including hypertelorism, a long narrow prominent forehead, long philtrum, thin lips, sparse eyelashes, cranial asymmetry, small hands and feet, short inferior limbs, and hypospadias have also been described. Antenatally, neurodevelopmental lesions, craniofacial dysmorphisms, and fetal akinesia deformation sequence/ arthrogryposis multiplex congenita may be present. Equal numbers of affected males and females have been identified. Males typically present with severe neonatal lactic acidosis while the presentation in females is more variable, dependent upon the pattern of X-inactivation. Females have been reported with a severe phenotype that includes microcephaly, spastic quadriplegia, severe epilepsy and cortical/subcortical atrophy.

Tests Available

Forms and Documents

Test Details

PDHA1
  • 1. Confirmation of biochemical diagnosis
  • 2. Carrier testing
  • 3. Prenatal diagnosis in at risk pregnancies
  • Capillary Sequencing

Ordering

461
4-5 weeks
2-5 mL Blood - Lavender Top Tube
Oral Rinse (30-40 mL) | Buccal Swabs

Billing

81406x1
No
Yes
  • 276.2 Acidosis Acidosis
  • 277.87 Disorders of mitochondrial metabolism, Kearns-Sayre syndrome, Mitochondrial Encephalopathy, Lactic Acidosis and Stroke-like episodes (MELAS syndrome), Mitochondrial Neurogastrointestinal Encephalopathy syndrome (MNGIE), Myoclonus with Epilepsy and with Ragged Red Fibers (MERRF syndrome), Neuropathy, Ataxia and Retinitis Pigmentosa (NARP syndrome)
  • 330.8 Other specified cerebral degenerations in childhood, Alpers' disease or gray-matter degeneration, Infantile necrotizing encephalomyelopathy, Leigh's disease, Subacute necrotizing, encephalopathy or encephalomyelopathy
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References

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  2. Pirot et al. (2016) J. Neuropathol. Exp. Neurol. 75 (3):227-38 (PMID: 26865159)
  3. Winters et al. (2017) Eur. J. Paediatr. Neurol. 21 (5):745-753 (PMID: 28495245)
  4. Brown et al. (2006) Dev Med Child Neurol 48 (9):756-60 (PMID: 16904023)
  5. Imbard et al. (2011) Molecular Genetics And Metabolism 104 (4):507-16 (PMID: 21914562)
  6. Stenson et al. (2014) Human Genetics 133 (1):1-9 (PMID: 24077912)
  7. Lissens et al. (2000) Human Mutation 15 (3):209-19 (PMID: 10679936)
  8. Ridout et al. (2008) Hum. Genet. 124 (2):187-93 (PMID: 18709504)
  9. Kara et al. (2017) Neuromuscul. Disord. 27 (1):94-97 (PMID: 27894792)
  10. Qin et al. (2016) J Mol Diagn 18 (3):446-53 (PMID: 26944031)