EARLY-ONSET CEREBELLAR-ATAXIA, MYOCLONUS AND HYPOGONADISM IN A CASE OF MITOCHONDRIAL COMPLEX-III DEFICIENCY TREATED WITH VITAMIN-K3 AND VITAMIN-C

A 16-year-old girl presented with early-onset cerebellar ataxia, myocl onus, elevated lactic acidosis and hypogonadotropic hypogonadism. Musc le biopsy specimens revealed fibres with a ''ragged'' appearance with increased mitochondria and lipid droplets. Biochemical investigation r evealed a deficiency of complex bc(1) (complex III) of the mitochondri al respiratory chain. Genetic analysis did not show either deletions o r known mutations of mitochondrial DNA (mtDNA). Phosphorus magnetic re sonance spectroscopy (P-31-MRS) showed defective energy metabolism in brain and gastrocnemius muscle. A decreased phosphocreatine (PCr) cont ent was found in the occipital lobes accompanied by normal inorganic p hosphate (Pi) and cytosolic pH. These findings represented evidence of a high cytosolic adenosine diphosphate concentration and a relatively high rate of metabolism accompanied by a low phosphorylation potentia l. Muscle P-31-MRS showed a high Pi content at rest, abnormal exercise transfer pattern and a low rate of PCr postexercise recovery. These f indings suggested a deficit of mitochondrial function. Therapy with vi tamins K-3 and C normalized brain P-31-MRS indices, whereas it did not affect muscle bioenergetic metabolism. In this patient, the endocrino logical disorder is putatively due to a mitochondrial cytopathy. Altho ugh an unknown mtDNA mutation cannot be ruled out, the genetic defect may lie in the nuclear genome.