Phosphoglycerate mutase deficiency: case report of a manifesting heterozygote with a novel E154K mutation and very late onset

Excerpt

Phosphoglycerate mutase (PGAM) deficiency is a rare glycogen storage disease (glycogenosis type X) due to recessive mutations in the muscle-specific isoform PGAM-M. We present a 67-year-old German patient with exercise-induced cramps and myalgia for 1 year but no attacks of rhabdomyolysis. CK was 2.5-folds increased and forearm exercise test was normal. Sections of the muscle biopsy stained with PAS showed moderate glycogen accumulation. Gomori-trichome and NADH showed subsarcolemmal depositions (0.01% of the fibres) suggesting tubular aggregates (Fig. 1). PGAM activity in muscle homogenate [4] was moderately reduced (141 U/g wet weight, normal 332 ± 88). Deficiencies of alpha-glucosidase, myophosphorylase, CPT and MAD were excluded biochemically. The PGAM-M gene was amplified [5] and directly sequenced. A novel G to A transition at nucleotide position 460, resulting in exchange of amino acid glutamic acid at codon 154 to lysine, was identified in heterozygous state. This was confirmed by reverse sequencing. RFLP analysis in 70 normal controls from the same ethnic origin did not show the mutation.

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