Neurological Involvement in Glycogen Storage Disease Type IXa due to PHKA2 Mutation

Can J Neurol Sci. 2020 May;47(3):400-403. doi: 10.1017/cjn.2020.18.

Abstract

Glycogen storage diseases (GSDs) result from the deficiency of enzymes involved in glycogen synthesis and breakdown into glucose. Mutations in the gene PHKA2 encoding phosphorylase kinase regulatory subunit alpha 2 have been linked to GSD type IXa. We describe a family with two adult brothers with neonatal hepatosplenomegaly and later onset of hearing loss, cognitive impairment, and cerebellar involvement. Whole-exome sequencing was performed on both subjects and revealed a shared hemizygous missense variant (c.A1561G; p.T521A) in exon 15 of PHKA2. The phenotype broadens the clinical and magnetic resonance imaging spectrum of GSD type IXa to include later onset neurological manifestations.

Keywords: Cerebellar atrophy; Exome sequencing; Glycogen storage disease; PHKA2.

Publication types

  • Case Reports

MeSH terms

  • Adult
  • Brain / diagnostic imaging
  • Cerebellar Ataxia / physiopathology*
  • Cognitive Dysfunction / physiopathology*
  • Epilepsy / physiopathology*
  • Exome Sequencing
  • Fecal Incontinence / physiopathology
  • Genetic Diseases, X-Linked / genetics
  • Genetic Diseases, X-Linked / physiopathology*
  • Glycogen Storage Disease / genetics
  • Glycogen Storage Disease / physiopathology*
  • Hearing Loss, Sensorineural / physiopathology*
  • Hepatomegaly / physiopathology
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Mutation, Missense
  • Pedigree
  • Peripheral Nervous System Diseases / physiopathology*
  • Phenotype
  • Phosphorylase Kinase / genetics*
  • Siblings
  • Splenomegaly / physiopathology

Substances

  • PHKA2 protein, human
  • Phosphorylase Kinase

Supplementary concepts

  • Glycogen Storage Disease, Type IXA2