A NEW CASE OF MULTIPLE MITOCHONDRIAL ENZYME DEFICIENCIES WITH DECREASED AMOUNT OF HEAT-SHOCK-PROTEIN-60

BRIONES P VILASECA MA RIBES A VERNET A LLUCH M CUSI V HUCKRIEDE A AGSTERIBBE E

P. Briones et al., A NEW CASE OF MULTIPLE MITOCHONDRIAL ENZYME DEFICIENCIES WITH DECREASED AMOUNT OF HEAT-SHOCK-PROTEIN-60, Journal of inherited metabolic disease, 20(4), 1997, pp. 569-577

32

INGLESE

Article

Endocrynology & Metabolism","Genetics & Heredity

Journal of inherited metabolic disease → ACNP

0141-8955

20

4

1997

569 - 577

ISI

0141-8955(1997)20:4<569:ANCOMM>2.0.ZU;2-L

Heat shock protein 60 (hsp60) is a mitochondrial matrix protein involv ed in the folding and correct assembly of polypeptides into complex mi tochondrial enzymes. Its deficiency has recently been described as the most likely primary cause of congenital lactic acidaemia with multipl e mitochondrial enzyme deficiencies in a female patient, We describe a new case of a girl with a substantially decreased amount of hsp60 in cultured fibroblasts. She presented from birth with hypotonia, unusual facial features, feeding difficulties and failure to thrive. Death oc curred at age 4.5 years. Biochemical findings included metabolic acido sis with lactic acidaemia, hyperammonaemia and intermittent ketosis. I n contrast to the previously reported case, organic acid analysis show ed an altered profile throughout her life. In agreement with this prof ile, various mitochondrial enzyme activities were deficient in culture d fibroblasts, including enzymes of die respiratory chain and the Kreb s cycle, the pyruvate dehydrogenase complex and the mitochondrial biot in-dependent carboxylases. Fibroblast mitochondria showed ultrastructu ral abnormalities, were swollen, and were mainly localized around the nucleus. The description of a second case of multiple mitochondrial en zyme deficiencies with reduced amount of hsp60 supports the idea that hsp60 deficiency might be a more common cause of mitochondrial disease . This opens new possibilities for the diagnosis and understanding of congenital lactic acidaemia.