Various classes of mutations in patients with phosphofructokinase deficiency (Tarui's 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 autosomal recessive trait. The clinical manifestations are similar to those in myophosphorylase deficiency (McArdle's disease), and the diagnosis required demonstration of the enzyme defect in muscle biopsy. In the Western hemisphere PFK deficiency appears to be prevalent among people of Ashkenazi Jewish descent. To define the molecular basis of this myopathy, we have studied 11 Ashkenazi and 2 non-Ashkenazi families with the disease. Ashkenazi patients share two common pathogenic mutations, a splicing defect and a nucleotide deletion, which account for approximately 95% of mutant alleles. The molecular diagnosis is now possible in this population by using simple PCR-based tests to screen for these mutations.