A novel PHKA2 mutation in a Chinese child with glycogen storage disease type IXa: a case report and literature review

Junling Fu,Tong Wang,Xinhua Xiao

doi:10.1186/s12881-019-0789-8

Abstract

BackgroundPHKA2 gene mutations can cause liver phosphorylase kinase (PhK) deficiency, resulting in glycogen storage disease type IXa (GSD IXa). Elevated liver transaminase levels and liver enlargement are the most frequent phenotypes of GSD IXa. However, whether the phenotypes are applicable to Chinese patients remains unclear.Case reportA boy aged 2 years and 8 months with a history of episodic fatigue and weakness since he was 2 years old was referred to our endocrinology clinic. Apart from symptomatic ketotic hypoglycemic episodes (palpitation, hand shaking, sweating, etc.), no abnormalities of liver transaminase levels or liver size were found. To identify the aetiology of his clinically diagnosed hypoglycaemia, the proband and his parents were screened for PHKA2 gene mutations by next-generation sequencing. A heterozygous mutation (c.2972C > G, p.G991A) in PHKA2 was found in the proband and his mother. Twenty-one Chinese cases with GSD IXa have been reported in the literature to date, and elevated liver transaminase levels (95%) and liver enlargement (91%) are the most frequent phenotypes of GSD IXa in Chinese patients. Hypoglycaemia may be one of the early onset symptoms in infants with GSD IXa.ConclusionsThis study enriches our knowledge of the PHKA2 gene mutation spectrum and provides further information about the phenotypic characteristics of Chinese GSD IXa patients.

Highlights

PHKA2 gene mutations can cause liver phosphorylase kinase (PhK) deficiency, resulting in glycogen storage disease type IXa (GSD IXa)
This study enriches our knowledge of the PHKA2 gene mutation spectrum and provides further information about the phenotypic characteristics of Chinese Glycogen storage diseases (GSDs) IXa patients
Molecular results Through data mining combined with genetic characteristics and clinical manifestations, we identified a novel heterozygous c.2972C > G mutation in PHKA2 of the proband, which is considered to be the pathogenic mutation

Summary

Introduction

PHKA2 gene mutations can cause liver phosphorylase kinase (PhK) deficiency, resulting in glycogen storage disease type IXa (GSD IXa). Elevated liver transaminase levels and liver enlargement are the most frequent phenotypes of GSD IXa. whether the phenotypes are applicable to Chinese patients remains unclear. Twenty-one Chinese cases with GSD IXa have been reported in the literature to date, and elevated liver transaminase levels (95%) and liver enlargement (91%) are the most frequent phenotypes of GSD IXa in Chinese patients. The subunits possess tissue-specific isoforms encoded by different genes [2]. The liver-specific isoforms of the α-, β- and γ-subunits are encoded by PHKA2, PHKB and PHKG2, respectively [2]. GSD IXa (MIM: 306000), due to a defect in the liver-particular α isoform (PHKA2), shows X-linked recessive inheritance characteristics [3]

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