title: Zellweger syndrome and secondary mitochondrial myopathy.
abstract: Defects in peroxisomes such as those associated with Zellweger syndrome (ZS) can influence diverse intracellular metabolic pathways, including mitochondrial functioning. We report on an 8-month-old female infant and a 6-month-old female infant with typical clinical, radiological and laboratory features of Zellweger syndrome; light microscopic and ultrastructural evidence of mitochondrial pathology in their muscle biopsies; and homozygous pathogenic mutations of the PEX16 gene (c.460 + 5G > A) and the PEX 12 gene (c.888_889 del p.Leu297Thrfs*12), respectively. Additionally, mitochondrial respiratory chain enzymology analysis in the first girl showed a mildly low activity in complexes II-III and IV. We also review five children previously reported in the literature with a presumptive diagnosis of ZS and additional mitochondrial findings in their muscle biopsies. In conclusion, this is the first study of patients with a molecularly confirmed peroxisomal disorder with features of a concomitant mitochondrial myopathy and underscores the role of secondary mitochondrial dysfunction in Zellweger syndrome, potentially contributing to the clinical phenotype.
authors.affiliation: Department of Paediatric Neurology, Chelsea and Westminster NHS Foundation Trust, London, UK, v.salpietro@imperial.ac.uk.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Salpietro
authors.forename: Rahul
authors.initials: R
authors.lastname: Phadke
authors.forename: Anand
authors.initials: A
authors.lastname: Saggar
authors.forename: Iain P
authors.initials: IP
authors.lastname: Hargreaves
authors.forename: Robert
authors.initials: R
authors.lastname: Yates
authors.forename: Christos
authors.initials: C
authors.lastname: Fokoloros
authors.forename: Kshitij
authors.initials: K
authors.lastname: Mankad
authors.forename: Jozef
authors.initials: J
authors.lastname: Hertecant
authors.forename: Martino
authors.initials: M
authors.lastname: Ruggieri
authors.forename: David
authors.initials: D
authors.lastname: McCormick
authors.forename: Maria
authors.initials: M
authors.lastname: Kinali
mesh_terms: D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008928:Mitochondria / Q000473:pathology*; D017240:Mitochondrial Myopathies / Q000150:complications / Q000175:diagnosis* / Q000235:genetics; D009154:Mutation; D015211:Zellweger Syndrome / Q000150:complications / Q000175:diagnosis* / Q000235:genetics