A new case of multiple mitochondrial enzyme deficiencies with decreased amount of heat shock protein 60 P. BRIONES 1 *, M. A. V ILASECA 1,2 , A. RIBES 1 , A. VERNET 2 , M. LLUCH 1 , V. C USI 2 , A. HUCKRIEDE 3 and E. AGSTERIBBE 3 1 Institut de Bioquímica Clínica, Corporació Sanitària i CSIC, Barcelona; 2 Serveis de Bioquímica, Neuropediatria i Anatomia Patològica, Hospital Universitari Sant Joan de Déu, Barcelona, Spain; 3 Laboratory of Physiological Chemistry, University of Groningen, Groningen, The Netherlands *Correspondence: Institut de Bioquímica Clínica, c/. Mejía Lequerica s/n, Edifici Helios III planta baixa, 08028, Barcelona, Spain MS received 15.10.96 Accepted 18.12.96 Summary: Heat shock protein 60 (hsp60) is a mitochondrial matrix protein involved in the folding and correct assembly of polypeptides into complex mito- chondrial enzymes. Its deficiency has recently been described as the most likely primary cause of congenital lactic acidaemia with multiple 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 occurred at age 4.5 years. Biochemical findings included metabolic acidosis with lactic acidaemia, hyperammonaemia and intermittent ketosis. In contrast to the previously reported case, organic acid analysis showed an altered profile throughout her life. In agreement with this profile, various mitochondrial enzyme activities were deficient in cultured fibroblasts, including enzymes of the respiratory chain and the Krebs cycle, the pyruvate dehydrogenase complex and the mitochondrial biotin- dependent carboxylases. Fibroblast mitochondria showed ultrastructural abnormali- ties, were swollen, and were mainly localized around the nucleus. The description of a second case of multiple mitochondrial enzyme 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. Cases of congenital lactic acidaemia characterized by lowered activities of a number of mitochondrial (mt) enzymes are reported with increasing frequency (Ruitenbeek et al 1989; Robinson et al 1992; Ibel et al 1993). How these multiple mitochondrial enzyme deficiencies arise is still not completely understood. Combined deficiencies of respiratory J. Inher. Metab. Dis. 20 (1997) 569– 577 © SSIEM and Kluwer Academic Publishers. Printed in the Netherlands 569