Medicina molecular y genética

Two Cases of X-linked Liver Glycogenosis in Hunan Province: Transmission from the Undiagnosed Maternal Grandfather

Abstract

Li P, Xu T, Xie X, Zhang Z, Hu Y and Lao Y

X-linked liver glycogenosis (XLG), also known as glycogen storage disease (GSD) type-IXa, is characterized by hepatomegaly, abnormal liver functions and growth retardation. This disease is a result of a deficiency of hepatic phosphorylase kinase (PHK), which plays an important role in glycogen metabolism by activating phosphorylase. We aim at identifying the genetic cause of the GSD running in a family with two affected boys, and hence develop proper management and genetic counseling. The boys presented with typical GSD signs and symptoms. The histology of the liver biopsy from the old brother showed glycogen accumulation in hepatocytes and confirmed his condition of GSD. The younger brother did not have a biopsy. Whole exome sequencing was used to analyze the genetic structure of the proband patients and their parents. Sanger sequencing was used to validate and confirm the identified mutation. The results showed that there was a known pathogenic mutation (p.E1125K) in PHKA2 gene located on chromosome Xp22, which encodes the regulatory subunit of PHK. Pedigree analysis revealed that the mother was a carrier, and the disease of both brothers was transmitted through their undiagnosed maternal grandfather. This is the first report of XLG caused by this mutation in China, and it indicated that GSD may be undiagnosed or underestimated since GSD IXa is one of the mild form of glycogenosis in terms of clinical symptoms. However, it is necessary to identify the genetic cause in order to perform effective intervention and genetic counseling.