VARIOUS CLASSES OF MUTATIONS IN PATIENTS WITH PHOSPHOFRUCTOKINASE DEFICIENCY (TARUIS DISEASE)

Muscle phosphofructokinase (PFK-M) deficiency (glycogenosis type VII, Tarui's disease) is characterized by intolerance to vigorous exercise, often accompanied by myoglobinuria. The disease is inherited as an au tosomal recessive trait. The clinical manifestations are similar to th ose in myophosphorylase deficiency (McArdle's disease), and the diagno sis required demonstration of the enzyme defect in muscle biopsy. In t he Western hemisphere PFK deficiency appears to be prevalent among peo ple of Ashkenazi Jewish descent. To define the molecular basis of this myopathy, we have studied 11 Ashkenazi and 2 non-Ashkenazi families w ith the disease. Ashkenazi patients share two common pathogenic mutati ons, a splicing defect and a nucleotide deletion, which account for si milar to 95% of mutant alleles. The molecular diagnosis is now possibl e in this population by using simple PCR-based tests to screen for the se mutations. (C) 1995 John Wiley and Sons, Inc.