GLYCOGENOSES AND LIPID DISORDERS DNA ANALYSIS
Myophosphorylase deficiency
Muscle phosphorylase deficiency (GSD type V, McArdle's disease), is characterized clinically by exercise intolerance with premature fatigue, myalgia, cramps in exercising muscles, and recurrent myoglobinuria. Biochemically, there is a defect of myo-phosphorylase, the enzyme that initiates glycogen breakdown in muscle. Diagnosis can be based on the histochemical or biochemical demonstration of absent phosphorylase activity in muscle. Molecular studies have identified more than 30 mutations in the myophosphorylase gene. One of these, a nonsense mutation at codon 49, is found in more than 75% of American patients, whereas approximately 10% have a mutation at codon 204.
Phosphofructokinase (PFK) deficiency
Muscle phosphofructokinase (PFK) deficiency (GSD type VII, Tarui's disease), is characterized clinically by exercise intolerance, cramps, and myoglobinuria, together with signs of compensated hemolytic anemia and hyperuricemia. Biochemically, there is a defect of the muscle subunit of PFK, the rate-limiting enzyme in the glycolytic pathway. Diagnosis can be based on histochemical or biochemical demonstration of absent PFK activity in muscle. Molecular studies have demonstrated that a particular splicing mutation (exon 5 deletion) is present in more than 50% of Ashkenazi-Jewish patients with PFK deficiency.
Phosphoglycerate mutase (PGAM) deficiency
Muscle phosphoglycerate mutase (PGAM) deficiency (GSD type X) is characterized clinically by cramps, muscle necrosis, and myoglobinuria after strenuous exercise. Biochemically, there is a defect of the muscle subunit isoform of PGAM, an enzyme of terminal glycolysis. Diagnosis can be based on biochemical demonstration of absent PGAM activity in muscle. All US patients identified to date have been African-American, and all carry a nonsense mutation at codon 78, but one patient also carried a mutation at codon 89.
Carnitine palmitoyltransferase II (CPT II) deficiency
CPT II deficiency is the most common inherited disorder of lipid metabolism affecting skeletal muscle. Typically, it presents in young adults with recurrent episodes of paroxysmal myoglobinuria triggered by prolonged exercise, fasting, cold, or fever. CPT II is part of an enzyme system catalyzing the translocation of long-chain fatty acids from the cytosolic compartment into the mitochondrial matrix, where they undergo beta-oxidation. Diagnosis can be based on the biochemical demonstration of absent CPT II activity in muscle. Molecular studies have demonstrated a missense mutation converting a serine to leucine at amino acid position 113 (Ser113Leu) in more than 50% of patients.
Specimens:
We require approximately 6ml of blood in tubes containing ACD citrate solution (yellow top).
Shipping:
The blood should be sent at room temperature by overnight carrier to:
Dr. Ali Naini
Laboratory of Melocular Neurogenetics
Columbia University Medical Center
Department of Pathology
630 West 168th Street, VC15th Floor, Room 208
New York, NY 10032
Phone: 212-305-3947
FAX: 212-305-3986
CPT Codes:
3890, 83892, 83894, 83898 and 83912
Price:
$250 per point mutation. |
