title: Premature atherosclerosis with photomyoclonic epilepsy, deafness, diabetes mellitus, nephropathy, and neurodegenerative disorder in two brothers: a new syndrome?
abstract: We describe two brothers with sensorineural deafness, diabetes mellitus, progressive neurological deterioration with photomyoclonic epilepsy, and progressive deterioration in renal function, resulting in death in the third decade of life. Autopsy showed diffuse atherosclerosis and arteriolosclerosis of the systemic vasculature. There was no evidence of these abnormalities in the patients' 2 sisters or either parent. Mitochondrial enzyme analysis documented partial deficiencies of Complex III and IV of the respiratory chain. This deficiency was expressed in skin fibroblasts, kidney and liver but not in muscle. This suggests that the disease-causing mutation is either in the mitochondrial or nuclear DNA. Various modes of inheritance are considered, including maternal, autosomal recessive, or X-linked recessive. We suggest this is a new genetic syndrome characterized by an underlying metabolic disease and premature atherosclerosis, possibly of mitochondrial origin.
authors.affiliation: Division of Genetics and Paediatrics, Hospital for Sick Children, Toronto, Ontario, Canada.
authors.forename: A
authors.initials: A
authors.lastname: Feigenbaum
authors.forename: C
authors.initials: C
authors.lastname: Bergeron
authors.forename: R
authors.initials: R
authors.lastname: Richardson
authors.forename: J
authors.initials: J
authors.lastname: Wherrett
authors.forename: B
authors.initials: B
authors.lastname: Robinson
authors.forename: R
authors.initials: R
authors.lastname: Weksberg
mesh_terms: D000328:Adult; D000740:Anemia / Q000235:genetics; D001161:Arteriosclerosis / Q000235:genetics*; D003638:Deafness / Q000235:genetics*; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D004392:Dwarfism / Q000235:genetics; D004831:Epilepsies, Myoclonic / Q000235:genetics*; D017809:Fatal Outcome; D006312:Hearing Loss, Bilateral / Q000235:genetics; D006801:Humans; D008297:Male; D008928:Mitochondria / Q000473:pathology; D009404:Nephrotic Syndrome / Q000235:genetics*; D009468:Neuromuscular Diseases / Q000235:genetics*; D013577:Syndrome