Lactic acid elevation in extramitochondrial childhood neurodegenerative diseases.
We report three children, each of whom seemed to have a primary mitochondrial disorder at presentation but was eventually diagnosed with an extramitochondrial inherited metabolic disease. The first patient presented at 6 months with developmental delay. Magnetic resonance imaging showed an abnormal signal in the white matter, and magnetic resonance spectroscopy showed elevated lactate peaks. A muscle biopsy showed complex IV deficiency, but leukocyte measurement of galactosylceramide beta-galactosidase activity was markedly diminished, consistent with Krabbe's disease. The second patient presented 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 biopsy was diagnostic for Alexander's disease. These cases and others in the literature suggest that lactic acid elevation in the central nervous system can be found in a number of extramitochondrial neurologic diseases. Such diseases would constitute a third category of lactic acidosis.
Kang
P B
PB
Division of Neurology, Children's Hospital of Philadelphia and the University of Pennsylvania School of Medicine, 19104, USA.
Hunter
J V
JV
Kaye
E M
EM
D000140:Acidosis, Lactic / Q000175:diagnosis* / Q000235:genetics; D001921:Brain / Q000473:pathology; D003067:Coenzymes; D005260:Female; D006580:Genetic Carrier Screening; D020271:Heredodegenerative Disorders, Nervous System / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D019344:Lactic Acid / Q000378:metabolism; D007965:Leukodystrophy, Globoid Cell / Q000175:diagnosis* / Q000235:genetics; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008667:Metalloproteins / Q000172:deficiency* / Q000235:genetics; D000090006:Molybdenum Cofactors; D009460:Neurologic Examination; D011621:Pteridines
D003067:Coenzymes; D019344:Lactic Acid; D008667:Metalloproteins; D000090006:Molybdenum Cofactors; D011621:Pteridines; C022261:molybdopterin