title: A Japanese child with asymptomatic elevation of serum creatine kinase shows PTRF-CAVIN mutation matching with congenital generalized lipodystrophy type 4.
abstract: Congenital generalized lipodystrophy (CGL), characterized by generalized absence of adipose tissue, has heterogeneous causes. Recently, a novel type of CGL complicated by muscular dystrophy was categorized as CGL4 caused by PTRF-CAVIN deficiency. However, it is unknown whether CGL4 exhibits clinical abnormalities during the infantile period. Here, we describe the youngest Japanese case of CGL4-a Japanese girl with asymptomatic high serum creatine kinase (CK) levels at 3months old. She was referred to our hospital at 5months of age because of her elevated serum CK (2528IU/L). Generalized absence of adipose tissue was first recognized at 2years of age. Mutation analysis of genes known to be responsible for CGL1-3 failed to disclose any abnormalities. Instead, analysis of the PTRF-CAVIN gene encoding PTRF-CAVIN revealed compound heterozygous mutations, one allele contained an insertion (c.696_697insC) and the other allele harbored a novel nonsense mutation (c.512C>A). Our patient had low serum leptin and adiponectin levels and insulin resistance. Pathological studies on biopsied muscle disclosed mild dystrophic change and highly reduced expression of PTRF-CAVIN. It was concluded that our PTRF-CAVIN deficient patient showed not only CGL but also asymptomatic elevation of serum CK because of her mild muscle dystrophic change.
authors.affiliation: Department of Pediatrics, Graduate School of Medicine, Kobe University, Kobe, Japan.
authors.forename: Ery Kus
authors.initials: EK
authors.lastname: Dwianingsih
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Takeshima
authors.forename: Kyoko
authors.initials: K
authors.lastname: Itoh
authors.forename: Yumiko
authors.initials: Y
authors.lastname: Yamauchi
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Awano
authors.forename: Rusdy Ghazali
authors.initials: RG
authors.lastname: Malueka
authors.forename: Atsushi
authors.initials: A
authors.lastname: Nishida
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ota
authors.forename: Mariko
authors.initials: M
authors.lastname: Yagi
authors.forename: Masafumi
authors.initials: M
authors.lastname: Matsuo
mesh_terms: D052242:Adiponectin / Q000097:blood; D044466:Asian People / Q000235:genetics; D051242:Caveolin 1 / Q000235:genetics*; D002675:Child, Preschool; D003402:Creatine Kinase; D005260:Female; D006801:Humans; D007223:Infant; D007333:Insulin Resistance; D020738:Leptin / Q000097:blood; D052497:Lipodystrophy, Congenital Generalized / Q000235:genetics* / Q000503:physiopathology; D009136:Muscular Dystrophies / Q000235:genetics*; D010375:Pedigree; D016601:RNA-Binding Proteins / Q000235:genetics*
chemical_list: D052242:Adiponectin; C495540:CAV1 protein, human; C497835:CAVIN1 protein, human; D051242:Caveolin 1; D020738:Leptin; D016601:RNA-Binding Proteins; D003402:Creatine Kinase