G209. DUAL PATHOLOGY IN TWO HYPOTONIC CHILDREN WITH PRADER-WILLI SYNDROME AND MUSCLE MITOCHONDRIAL COMPLEX I DEFICIENCY

E. Wassmer, B.H. Robinson, I. Tein.

Dept. of Pediatrics, The Hospital for Sick Children, Toronto, Canada

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, thyroid function, VLCFAs, 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, SDH and COX were normal. E/M 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.

G210. ARC SYNDROME IS NOT ALLELIC TO PFIC I AND II

P. Gissen^1,3, C.A. Johnson^1,3, J. Stapelbroek …