Abstract
A white male, the product of a G1,PO non-consanguineous 34 wk. pregnancy presented in the first month of life with hypoglycemia, progressive lactic acidosis (5→31 mM, normal<2.5) with increased lactic/pyruvate ratio (64:1) and hyperalaninemia (2.3 mM, nl <.44). Total plasma carnitine was 25 uM (normal >37). GLC of urine showed no accumulation of organic acids. There was progressive hypotonia, hepatomegaly, brain CT abnormalities and respiratory insufficiency leading to death at 16 wks. Enzymatic determination on fibroblasts and liver/skeletal muscle biopsy ruled out pyruvate carboxylase, pyruvate dehydrogenase, PEPCK, glucose-6-phosphatase and fructose 1-6 bisphosphatase deficiencies. There was increased glycogen and lipid and giant mitochondria with concentric whorls in muscle. Freshly isolated mitochondria from 4 tissues revealed a marked deficiency of NAD linked respiration but normal succinate linked respiration. Reduction of cyt c by NADH (rotanone sensitive) in permeabilized mitochondria revealed a deficiency of Complex 1, e.g., 5 nmol cytC reduced/min/mg skeleton muscle (control 206). However, Complex 1 activity reactive to ferricyanide was identical to control, suggesting the deficiency was in the Fe:S centers of Complex 1. Electron paramagnetic resonance spectroscopy of liver sub-mitochondrial particles revealed a selective absence of Fe:S centers. This represents the first case of a deficiency of the Fe:S centers of mitochondrial Complex 1.
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Moreadith, R., Batshaw, M., Ohnishi, T. et al. MITOCHONDRIAL NADH - UBIQUINONE OXIDOREDUCTASE (Complex 1) DEFICIENCY IN AN INFANT WITH CONGENITAL LACTIC ACIDOSIS. Pediatr Res 18 (Suppl 4), 223 (1984). https://doi.org/10.1203/00006450-198404001-00782
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DOI: https://doi.org/10.1203/00006450-198404001-00782