Recurrent episodes of myoglobinuria, mental retardation and seizures but no hemolysis in two brothers with phosphoglycerate kinase deficiency

We report two brothers with mild intellectual deficiency, exercise intolerance, rhabdomyolysis, seizures and no hemolysis. Phosphoglycerate kinase (PGK) activity was strongly decreased in their red blood cells. Subsequent molecular analysis of PGK1 revealed hemizygosity for a novel mutation c.756 + 3A > G, in intron 7. Analysis of the effect of this mutation on pre-mRNA processing demonstrated markedly decreased levels of normal PGK1 mRNA. In addition, the c.756 + 3A > G change resulted in abnormally spliced transcripts. If translated, these transcripts mostly encode for C-terminally truncated proteins. The consequences of the c.756 + 3A > G mutation is discussed, as well as the genotype-to-phenotype correlation with regard to previously described mutations (PGK Fukuroi and PGK Antwerp), which also result in C-terminal truncated proteins.