title: An unusual presentation of copper metabolism disorder and a possible connection with Niemann-Pick type C.
abstract: Abnormal copper metabolism has been linked with neurological disorders, such as Wilson and Menkes disease. Another disorder causing symptoms similar to copper metabolism disorder is Niemann-Pick type C. However, a definite pathophysiological connection between Niemann-Pick type C and copper metabolism disorders has never been established. The authors present an adolescent with an unusual presentation of copper deficiency-dysarthria, ataxia, and vertical gaze paresis, without significant cognitive degeneration or pathological magnetic resonance imaging (MRI). The patient was found to carry 2 mutations in the NPC1 gene. A possible link, explaining how copper deficiency might induce the Niemann-Pick phenotype might involve overproduction of cholesterol and inhibition of acid sphingomyelinase. We suggest that copper metabolism disorders be included in the differential diagnosis for ataxia and dysarthria, even in cases with unusual presentations. Moreover, should the connection between copper and Niemann-Pick be validated, screening for copper metabolism disorders may be advisable in Niemann-Pick type C patients and vice-versa.
authors.affiliation: Stollery Children’s Hospital in Edmonton, Alberta, Canada. helly.goez@albertahealthservices.ca
authors.forename: Helly R
authors.initials: HR
authors.lastname: Goez
authors.forename: Francois D
authors.initials: FD
authors.lastname: Jacob
authors.forename: Robert D
authors.initials: RD
authors.lastname: Fealey
authors.forename: Marc C
authors.initials: MC
authors.lastname: Patterson
authors.forename: Vijay
authors.initials: V
authors.lastname: Ramaswamy
authors.forename: Rabin
authors.initials: R
authors.lastname: Persad
authors.forename: Edward S
authors.initials: ES
authors.lastname: Johnson
authors.forename: Jerome Y
authors.initials: JY
authors.lastname: Yager
mesh_terms: D000293:Adolescent; D002352:Carrier Proteins / Q000235:genetics; D003300:Copper / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008659:Metabolic Diseases / Q000150:complications* / Q000235:genetics / Q000473:pathology; D009154:Mutation / Q000235:genetics; D000077296:Niemann-Pick C1 Protein; D009542:Niemann-Pick Diseases / Q000150:complications* / Q000235:genetics / Q000473:pathology
chemical_list: D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; C106881:NPC1 protein, human; D000077296:Niemann-Pick C1 Protein; D003300:Copper