molybdenum-cofactor and Acidosis--Lactic

Molybdenum cofactor deficiency leads to combined deficiency of sulfite oxidase, xanthine dehydrogenase, and aldehyde oxidase enzyme activities. The major clinic symptom is intractable seizures seen soon after birth. No definite therapy is available. We report here a newborn with molybdenum cofactor deficiency-associated Dandy-Walker malformation who presented with severe lactic acidosis and intracranial hemorrhage.

Topics: Acidosis, Lactic; Coenzymes; Dandy-Walker Syndrome; Female; Humans; Infant, Newborn; Intracranial Hemorrhages; Metabolism, Inborn Errors; Metalloproteins; Molybdenum Cofactors; Pteridines

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.

Topics: Acidosis, Lactic; Brain; Coenzymes; Female; Genetic Carrier Screening; Heredodegenerative Disorders, Nervous System; Humans; Infant; Infant, Newborn; Lactic Acid; Leukodystrophy, Globoid Cell; Magnetic Resonance Imaging; Magnetic Resonance Spectroscopy; Male; Metalloproteins; Molybdenum Cofactors; Neurologic Examination; Pteridines

Molybdenum cofactor deficiency was diagnosed in a 3-month-old girl who presented with microcephaly, developmental delay, severe irritability, and lactic acidosis. Dietary methionine restriction, with cysteine supplementation, was associated with moderate short-term clinical improvement, including a resumption in predicted head growth, modest developmental progress, and a reduction in irritability. Clinical relapse was associated with noncompliance of dietary therapy 2 months later. Urinary sulfite levels measured by commercial dipsticks were useful in following therapy. Molybdenum cofactor deficiency is probably frequently underdiagnosed due to the lack of specific clinical or laboratory features. Screening of infants at risk for the presence of urinary sulfites or serum hypouricemia, or both, is both rapid and inexpensive.

Topics: Acidosis, Lactic; Coenzymes; Cysteine; Developmental Disabilities; Female; Food, Fortified; Humans; Infant; Lactates; Metabolism, Inborn Errors; Metalloproteins; Methionine; Microcephaly; Molybdenum Cofactors; Pteridines