Key words Pyruvate dehydrogenase E1α
Springer Online Journal Archives 1860-2000
Abstract Pyruvate dehydrogenase (PDH) complex deficiency, a common cause of congenital lactic acidosis, is mostly due to mutations in the X-linked gene coding for the E1α subunit of the complex. We have studied two unrelated girls presenting a static encephalopathy with spastic quadriplegia, microcephaly and seizures and in one girl, hypocalcaemia, a new finding in PDH complex deficiency. PDH deficiency was diagnosed in adolescence and both girls had low PDH complex activity in muscle but normal amounts of all subunits on Western blotting, and a normal lactate/pyruvate ratio in blood and CSF. Mutation analysis of the E1α gene at the cDNA or DNA level revealed an arginine to histidine substitution at amino acid position 288 (R288H) in the girl with hypocalcaemia and a 12 bp insertion, predicting a four amino acid duplication at the c-terminal end of the protein in the second girl. They both carried a normal and a mutated E1α gene and X-inactivation studies showed skewed patterns. Conclusion Mutation identification in pyruvate dehydrogenase complex deficiency remains important especially for the determination of the recurrence risk and for reliable genetic counselling in couples with an affected child.
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