Lactic acid elevation in extramitochondrial childhood neurodegenerative diseases

We report three children, each of whom seemed to have a primary mitochondri al disorder at presentation but was eventually diagnosed with an extramitoc hondrial inherited metabolic disease. The first patient presented at 6 mont hs with developmental delay. Magnetic resonance imaging showed an abnormal signal in the white matter, and magnetic resonance spectroscopy showed elev ated lactate peaks. A muscle biopsy showed complex IV deficiency, but leuko cyte measurement of galactosylceramide beta -galactosidase activity was mar kedly diminished, consistent with Krabbe's disease. The second patient pres ented at birth with seizures and later had developmental delays. There was brain atrophy on neuroimaging. Serum and cerebrospinal fluid lactate levels were elevated. She had persistently elevated urine thiosulfate, which was diagnostic for molybdenum cofactor deficiency. The third child presented at 2 months with seizures and hypotonia. Magnetic resonance imaging showed an abnormal signal in the basal ganglia and surrounding white matter, whereas magnetic resonance spectroscopy showed elevated lactate peaks. A brain bio psy was diagnostic for Alexander's disease. These cases and others in the l iterature suggest that lactic acid elevation in the central nervous system can be found in a number of extramitochondrial neurologic diseases. Such di seases would constitute a third category of lactic acidosis.