ピルビン酸脱水素酵素複合体異常症女児患者の遺伝子診断システムの確立

Pyruvate dehydrogenase (PDH) complex deficiency is one of the important causes of congenital lactic acidemia and mostly due to defect in the α subunit of PDH (E1α), of which gene is located on the X chromosome. The diagnosis of the PDH E1α deficiency is usually established by the measurement of the PDH complex activity in cultured cells.
However, some female patients, who are heterozygous for the mutant allele, cannot be diagnosed only by the assay of PDH complex activity, because of the skewed X-chromosome inactivation in cultured cells. Then, we established DNA diagnostic system for PDH E1α deficiency using X inactivation assay, no RI PCR-SSCP, and direct sequencing. With this DNA diagnostic system we could diagnose 4 female patients as PDH E1α deficiency from 14 female patients who were suspected PDH complex deficiency from the clinical features and concentrations of lactate and pyruvate in the blood but showed normal PDH complex activity in their cultured cells. These results indicate that this DNA diagnostic system for PDH E1 αdeficiency is very useful.