T.p.30

We report two brothers, aged 14 and 16, with a mild intellectual deficiency. Both brothers presented recurrent episodes of generalized weakness following effort since the age of 4. At the age of 8, after spending twenty minutes playing in a swimming pool, the youngest brother presented an episode of weakness, together with a painful swelling of the left thigh and myoglobinuria (max CK 540,000 UI/l). He was hospitalized in an intensive care unit and treated by intravenous fluids and loop diuretics. 4 months later, a muscle biopsy disclosed abnormal vacuolisation with slightly increased muscle lipid content. An extensive workup excluded a mitochondrial disease, a defect of fatty acid oxidation and Mac Ardle disease. At the age of 13, the youngest brother presented a refractory status epilepticus, complicated by rhabdomyolysis and acute renal failure (max CK 710,000 UI/l). Physical examination of both brothers, between acute episodes, was completely normal and CK level was approximately 500 UI/l ( N PGK1 gene sequencing revealed a splice site consensus sequence change that co-segregates with decreased PGK activity. Its putative functional consequences are currently under investigation. Conclusion: Phosphoglycerate kinase (PGK) deficiency, a rare defect in glycolysis pathway, has its place in the differential diagnosis of metabolic myopathies. The association of exercise intolerance and recurrent episodes of myoglobinuria with haemolytic anaemia, intellectual deficiency or epilepsy is highly suggestive of the disease.