Glycogen Storage Disorder Type IXb: Exploring Clinical Patterns and Genetic Insights Into a Rare Phosphorylase Kinase B (PHKB)-Associated Case

TL;DR

This paper reports a rare case of GSD IXb caused by a deletion in the PHKB gene, highlighting the importance of genetic testing for accurate diagnosis.

Contribution

The study presents a rare deletion mutation in the PHKB gene and emphasizes the genetic diversity in GSD IXb cases.

Findings

A homozygous deletion in exons 2 to 10 of the PHKB gene was identified in a patient with GSD IXb.

Clinical features included hypoglycemia, hepatosplenomegaly, and glycogen accumulation confirmed by histology.

The case underscores the need for individualized diagnosis due to genetic heterogeneity in GSD IXb.

Abstract

Glycogen storage disorders (GSDs) encompass a group of metabolic disorders resulting from deficiencies in enzymes involved in glycogen synthesis or breakdown. Among these, GSD type IX manifests due to a deficiency in phosphorylase kinase enzyme, leading to liver-specific, muscle-specific, or combined forms of the disorder. We present a case report of an exceedingly rare deletion-type mutation in the phosphorylase kinase B (PHKB) gene causing GSD type IXb, offering a comprehensive evaluation of clinical, laboratory, and molecular findings. A one-year and four-month-old male, born of third-degree consanguinity, presented with delayed motor milestones, hypotonicity, short stature, doll-like facies, and hepatosplenomegaly. Preliminary investigations revealed fasting hypoglycemia, ketonuria, elevated liver enzymes, and histological evidence of glycogen accumulation. Whole exome sequencing identified a homozygous deletion encompassing exons 2 to 10 of the PHKB gene, confirming the diagnosis of GSD IXb. GSD IXb due to PHKB mutations is rare, comprising only 10% of liver-specific GSD IX cases. Compared with similar cases reported in the literature, our analysis highlights the genetic heterogeneity within this subtype. Although clinical manifestations may overlap, specific genetic alterations vary, indicating that an individualized diagnostic approach is needed.

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