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Arch Dis Child. 2003 Apr. Abstract: Aim & Method: To describe the features of two children with Prader-Willi Syndrome (PWS) and Complex-1 deficiency. Results: Two children presented as neonates with hypotonia, feeding difficulties and growth retardation. Development was subsequently delayed. CPK [creatine kinase], thyroid function, VLCFAs [very long-chain fatty acids], ammonia and organic acids were normal. Serum lactate was normal in Case 1 and mildly elevated in Case 2. ABRs revealed delayed conductions of waves I-III. VEPs, EMG, NCS were normal. Neuroimaging showed mild cerebral volume loss. Muscle biopsy revealed a normal checkerboard pattern of Type I and II fibres and 1 mottled fibre (Gomori-trichrome staining) in Case I. Type II fibres predominated in Case 2. Mitochondrial stains for NADH, LDH [lactate dehydrogenase], SDH [succinate dehydrogenase] and COX [cytochrome C oxidase] were normal. E/M [electron microscopy] revealed normal mitochondria and no lipid or glycogen accumulation. Mitochondrial enzyme analysis demonstrated unmeasurable NADH cytochrome-C-reductase activity in Case 1 and decreased activity of 11.7 nmol/min/mg mitochondrial protein (controls 94.6± 9.5) in Case 2. Succinate cytochrome-C-reductase activity was reduced in Case 2 at 47 (controls 102 ± 6.9) but normal in Case 1. COX activities were normal. In skin fibroblasts the lactate/pyruvate ratio was slightly elevated. The Prader-Willi phenotype became evident after 1 year of age. No deletion was detected in region 15q11-q13 with G-banding or FISH, however the methylation pattern was abnormal. Parental samples confirmed maternal uniparental heterodisomy of PWS. Conclusion: The occurence of Complex-1 deficiency in PWS is likely a secondary rather than a primary event, but may contribute to the PWS clinical phenotype in certain cases. |