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PDHA1 Gene Analysis

Pyruvate dehydrogenase complex (PDC) deficiency results in a variety of phenotypes with metabolic and neurological manifestations. The metabolic abnormalities include elevated blood lactate and pyruvate (with a normal ratio) and specifically increased plasma alanine. Neurological manifestations may include hypotonia, lethargy, seizures, developmental delay, neuropathy and congenital or degenerative brain abnormalities.

The majority of PDC deficiencies result from mutations in the X-linked pyruvate dehydrogenase (E1) alpha subunit gene (PDHA1). Mutations of other PDC genes are less common. The sex ratio of PDH E1-alpha deficiency appears to be approximately 1 to 1. Heterozygous females may manifest severe symptoms, although generally they are less severely affected than males with similar mutations, and in some cases may be asymptomatic.

For patients with deficient PDC enzyme activity or strongly clinically suspected PDC deficiency, PDHA1 gene sequence analysis is recommended as the first step in mutation identification. PDHB gene sequence analysis is available as a follow-up test or can be ordered as the initial test when clinically indicated. PDHB known familial mutation analysis is available for family members when a mutation has been identified. PDHB prenatal diagnosis is also available for families who have had a mutation identified or by special arrangement in advance with the director.

Indications for Testing

  • Confirmation of biochemical or strongly suspected clinical diagnosis of pyruvate dehydrogenase complex deficiency.
  • Carrier testing in adult females with a family history of X-linked pyruvate dehydrogenase complex deficiency.
  • Targeted mutation analysis for known familial mutations in PDHA1.
  • Pregnancy known to be at risk for pyruvate dehydrogenase deficiency and a known PDHA1 familial mutation.

OMIM # 300502

Sample requirements

  • Infants: 2-3 mL whole blood in purple top EDTA tube
  • Children (>2 years) and adults: 3-4 mL whole blood in purple top EDTA tube
  • Amniotic fluid or cultured amniocytes
  • Chorionic villi or cultured chorionic villi

Contact laboratory genetic counselors or molecular director for specific sample requirements in advance.

Note: Maternal blood sample is also required for maternal cell contamination studies for prenatal samples. Send 3-4 mL purple top EDTA tube along with prenatal sample. Cultured skin fibroblasts, blood lymphocytes, and frozen tissue from fresh muscle or liver biopsies performed for enzyme analysis may also be used for DNA analysis. Cell line build up is available, as is DNA extraction and storage. Enzyme assay for PDC may be arranged directly with the Center for Inherited Disorders of Metabolism (CIDEM).

Sample Handling

Blood samples stored overnight should be refrigerated or kept cold. Blood samples should never be frozen. Specimens being sent from outside facilities should be packaged with a cold pack according to standard medical safety practices. The specimen should be shipped by overnight priority (scheduled to arrive by Friday morning at the latest).

Shipping Address

Center for Human Genetics Laboratory
10524 Euclid Avenue, Sixth Floor
Cleveland, OH 44106

For local samples, please call Client Service (216-844-5227) to arrange for sample pick-up.

Turnaround Time

PDHA1 Sequencing – 3 weeks
PDHA1 Known Familial Mutation analysis – 1 week
PDHA1 Prenatal Diagnosis – 1 week

CPT Codes

PDHA1 Gene Sequencing: 81405
PDHA1 Prenatal Analysis: 81405
PDHA1 Known Familial Mutation Analysis: 81403

Please submit a completed Molecular Requisition for each sample.