title: Distal vacuolar myopathy in nephropathic cystinosis.
abstract: Nephropathic cystinosis is a lysosomal storage disorder leading to renal failure by age 10 years. Prolonged patient survival following renal transplantation has allowed the development of previously unknown long-term complications. Muscle involvement has been reported in a single posttransplant cystinosis patient, but the range of clinical, electrophysiologic, and histologic features has not been fully described. Thirteen of 54 post-renal-transplant patients that we examined developed weakness and wasting in the small hand muscles, with or without facial weakness and dysphagia. Tendon reflexes were preserved and sensory examinations were normal. Electrophysiologic studies in 11 affected patients showed normal nerve conduction velocities and preserved sensory action potentials. The voluntary motor units in the affected distal muscles had reduced amplitude and brief duration, confirmed with quantitative electromyography in 4 patients. Biopsy of the severely affected abductor digiti minimi or extensor carpi radialis brevis muscles in 2 patients revealed marked fiber size variability, prominent acid phosphatase-positive vacuoles, and absence of fiber type grouping or inflammatory cells. Crystals of cystine were detected in perimysial cells but not within the muscle cell vacuoles. The muscle cystine content of clinically affected muscles was markedly elevated. We conclude that a distal vacuolar myopathy is a common late complication of untreated nephropathic cystinosis. Although the cause is unclear, the general lysosomal defect in this disease may also affect the lysosomes within muscle fibers.
authors.affiliation: Section on Human Biochemical Genetics, National Institute of Child Health and Human Development, Bethesda, MD 20892.
authors.forename: L R
authors.initials: LR
authors.lastname: Charnas
authors.forename: C A
authors.initials: CA
authors.lastname: Luciano
authors.forename: M
authors.initials: M
authors.lastname: Dalakas
authors.forename: R W
authors.initials: RW
authors.lastname: Gilliatt
authors.forename: I
authors.initials: I
authors.lastname: Bernardini
authors.forename: K
authors.initials: K
authors.lastname: Ishak
authors.forename: V A
authors.initials: VA
authors.lastname: Cwik
authors.forename: D
authors.initials: D
authors.lastname: Fraker
authors.forename: T A
authors.initials: TA
authors.lastname: Brushart
authors.forename: W A
authors.initials: WA
authors.lastname: Gahl
mesh_terms: D000293:Adolescent; D000328:Adult; D003553:Cystine / Q000378:metabolism; D003554:Cystinosis / Q000150:complications / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology / Q000378:metabolism / Q000473:pathology* / Q000503:physiopathology; D016030:Kidney Transplantation; D009135:Muscular Diseases / Q000209:etiology* / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009431:Neural Conduction; D014617:Vacuoles / Q000648:ultrastructure
chemical_list: D003553:Cystine