Test Code: 9661

Adenosine Monophosphate Deaminase 1 (AMPD1) Deficiency: AMPD1 Two Mutation Panel
Test Code: 9661
Turnaround time: 3 weeks

CONDITION DESCRIPTION

Adenosine monophosphate deaminase 1 (AMPD1) deficiency, also known as myoadenylate deaminase (MADA) deficiency, is a disorder of purine metabolism that leads to a deficiency in the production of ATP. It is the most common enzyme deficiency identified in muscle, with a prevalence of almost 2% in the general population. The typical age of presentation is late adolescence to early adulthood. Affected individuals have generalized exertional muscle pain, cramps and fatigue. Other presenting features include post-exertional myoglobinuria and rhabdomyolysis. Completely asymptomatic individuals have also been reported.

Serum creatine kinase (CK) is usually normal or only slightly elevated. Aerobic exercise testing is typically normal. Muscle histology is normal but muscle histochemistry shows reduced AMPD1 enzyme activity. AMPD1 deficiency is caused by mutations in the AMPD1 gene (1p21). AMPD1 deficiency is an autosomal recessive condition.

Two mutations, c.133C>T (p.Q45X, previously known as p.Q12X) and c.242C>T (p.P81L, previously known as p.P48L), account for the majority of reported mutations in Caucasians and African Americans. Full gene sequence analysis is also available for individuals with documented AMPD1 deficiency when no or one mutation identified by common mutation testing.

Reference:
Brian A. van Adel, et al. Metabolic Myopathies: Update 2009. J Clin Neuromusc Dis. 2009, 10(3): 97-121.

GENES
AMPD1

INDICATIONS
This test is indicated for:

  • Confirmation of a biochemical or clinical diagnosis of AMPD1 deficiency
  • Carrier testing in adults with a family history of AMPD1 deficiency

METHODOLOGY

Presence/absence of the p.Q12X and p.P48L mutations are detected by PCR amplification and sequencing of the resulting fragments.

DETECTION

All p.Q12X and p.P48L mutant alleles will be detected by this assay. Some studies have found that these two mutations account for the majority of reported mutations in Caucasians and African Americans. Prevalence of AMPD1 mutations in other ethnic groups is currently unknown.

SPECIMEN REQUIREMENT

Submit only 1 of the following specimen types

* Preferred specimen type: Whole Blood

Type: Whole Blood
Specimen Requirements:
In EDTA (purple top) or ACD (yellow top) tube: Infants (2 years): 3-5 ml
Older Children & Adults: 5-10 ml

Specimen Collection and Shipping: Refrigerate until time of shipment. Ship sample within 5 days of collection at room temperature with overnight delivery.

Type: Saliva
Specimen Requirements:
OrageneTM Saliva Collection kit (available through CEN4GEN) used according to manufacturer instructions.

Specimen Collection and Shipping: Store sample at room temperature. Ship sample within 5 days of collection at room temperature with overnight delivery.

SPECIAL INSTRUCTIONS
Submit copies of diagnostic biochemical test results with the sample, if appropriate.

RELATED TESTS

• Full gene sequence analysis of the AMPD1 gene is available if common mutation testing does not identify two mutations in a clinically and biochemically affected individual.
• A two-tiered rhabdomyolysis panel that includes testing for the two common AMPD1 mutations is also available.
• Custom diagnostic mutation analysis (test code: 6875) is available to family members if mutations are identified by targeted mutation testing or sequencing analysis.