title: Muscular dystrophy with large mitochondria associated with mutations in the CHKB gene in three British patients: extending the clinical and pathological phenotype.
abstract: Three patients with CHKB deficient muscular dystrophy are described which broadens the previously described phenotype. Blood smear in one patient showed Jordans anomaly (vacuolated leukocytes). Gastrointestinal features occurred in two patients and there appeared to be acute deterioration with infection/general anaesthesia. Brain imaging showed no structural changes but brain magnetic resonance proton spectroscopy (MRS) demonstrated significant reduction in choline:N-acetyl aspartate and choline:creatine ratios in keeping with a general decrease in the amount of choline and phosphocholine-based substrate. Muscle pathology showed either myopathic or dystrophic features, uneven oxidative enzyme staining, COX deficient fibres and peripherally located large mitochondria. CHKB activity was reduced in all three patients and complex 1 activity was significantly reduced in one patient.
authors.affiliation: Dubowitz Neuromuscular Centre, UCL Institute of Child Health & Great Ormond Street Hospital for Children, London, UK. r.quinlivan@ucl.ac.uk
authors.forename: Ros
authors.initials: R
authors.lastname: Quinlivan
authors.forename: Satomi
authors.initials: S
authors.lastname: Mitsuahashi
authors.forename: Caroline
authors.initials: C
authors.lastname: Sewry
authors.forename: Sebahattin
authors.initials: S
authors.lastname: Cirak
authors.forename: Chieko
authors.initials: C
authors.lastname: Aoyama
authors.forename: David
authors.initials: D
authors.lastname: Mooore
authors.forename: Stephen
authors.initials: S
authors.lastname: Abbs
authors.forename: Stephanie
authors.initials: S
authors.lastname: Robb
authors.forename: Tina
authors.initials: T
authors.lastname: Newton
authors.forename: Celia
authors.initials: C
authors.lastname: Moss
authors.forename: Daniel
authors.initials: D
authors.lastname: Birchall
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sugimoto
authors.forename: Kate
authors.initials: K
authors.lastname: Bushby
authors.forename: Michela
authors.initials: M
authors.lastname: Guglieri
authors.forename: Francesco
authors.initials: F
authors.lastname: Muntoni
authors.forename: Ichizo
authors.initials: I
authors.lastname: Nishino
authors.forename: Volker
authors.initials: V
authors.lastname: Straub
mesh_terms: D001921:Brain / Q000378:metabolism / Q000473:pathology; D002675:Child, Preschool; D002797:Choline Kinase / Q000235:genetics*; D002892:Chromosomes, Human, Pair 22; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D008297:Male; D008928:Mitochondria / Q000235:genetics*; D009136:Muscular Dystrophies / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D009154:Mutation / Q000235:genetics*; D010641:Phenotype; D055815:Young Adult
chemical_list: C542592:CHKB protein, human; D002797:Choline Kinase