Homozygosity ( @entity32750 ) in XXXX causes delayed infantile onset of cardiomyopathy and neuropathy.

@entity1 @entity32749 @entity375 @entity1184 @entity32750 @entity7319 @entity7748 @entity8433 @entity31771 @entity920 @entity70728 @entity21 @entity2057 @entity1121
OBJECTIVE: To report three unrelated @entity1 with a distinctive phenotype of @entity8433 , @entity2057 , and @entity1121 . The @entity1 all had a homozygous missense mutation in @entity32749 . BACKGROUND: @entity32749 encodes a @entity31771 , thought to function as a @entity920 transporter to cytochrome c oxidase (COX), the terminal enzyme of the respiratory chain. Mutations in @entity32749 have been described in @entity1 with severe @entity7319 and early onset fatal @entity1184 . All @entity1 so far reported are compound heterozygotes for a missense mutation ( @entity32750 ) near the predicted CxxxC metal binding motif; however, recent functional studies of the homologous mutation in @entity375 failed to demonstrate an effect on respiration. METHODS: Here we present clinical, biochemical, morphologic, functional, MRI, and @entity7748 data in two @entity1 , and a short report in an additional @entity1 , all carrying a homozygous @entity70728 transition ( @entity32750 ). RESULTS: The disease onset and symptoms differed significantly from those in compound heterozygotes. MRI and muscle morphology demonstrated an age-dependent progression of disease with predominant involvement of white matter, late appearance of @entity21 , and @entity2057 in addition to the relatively late onset of @entity1121 . The @entity920 uptake of cultured fibroblasts was significantly increased. CONCLUSIONS: The clinical spectrum of @entity32749 deficiency includes the delayed development of @entity1121 and severe @entity2057 . There is increased @entity920 uptake in @entity1 ' fibroblasts indicating that the @entity70728 mutation effects cellular @entity920 metabolism.
