X-linked glycogen storage disease IXa manifested in a female carrier due to skewed X chromosome inactivation.
BACKGROUND
Glycogen storage disease (GSD) is a group of inherited metabolic disorders due to enzymatic deficiency involved in glycogen breakdown. In various subtypes of GSD, GSD IXa is an X-linked recessive disorder, which only manifested in males. Here, we report a case of X-linked GSD IXa manifested in a female Chinese patient accompanying a skewed X-chromosome inactivation (XCI).


METHODS
A 29-y-old Chinese female was admitted to evaluate mild hepatomegaly, which was repeatedly observed in serial abdominal ultrasonographic examinations. GSDIXa was suspected. To identify the mutation and the disease mechanism, we performed sequencing analysis of the PHKA2 gene, XCI assay and cDNA expression analysis.


RESULTS
Sequencing analysis revealed a heterozygous mutation in the PHKA2 gene (c.3614C>T; p.P1205L) of the patient. In XCI assay, the proband showed a skewed XCI pattern cDNA expression analysis showed a preferential expression of the mutant allele in leukocytes of the patient.


CONCLUSIONS
This is a rare report of X-linked GSD IXa manifested in a female carrier with skewed XCI. Skewed XCI can play a key role in the manifestation of X-linked recessive disorders in female carriers.
Department of Pathology, The University of Hong Kong, Hong Kong, China; Department of Laboratory Medicine, School of Medicine, Kyung Hee University, Seoul, Republic of Korea.
Sun Young
SY
Cho
Ching-wan
CW
Lam
Sui-Fan
SF
Tong
Wai-Kwan
WK
Siu
D000328:Adult; D000483:Alleles; D002681:China; D041321:Chromosomes, Human, X / Q000235:genetics*; D004252:DNA Mutational Analysis; D005260:Female; D006008:Glycogen Storage Disease / Q000235:genetics*; D006801:Humans; D009154:Mutation; D010764:Phosphorylase Kinase / Q000235:genetics; D049951:X Chromosome Inactivation / Q000235:genetics*
D010764:Phosphorylase Kinase
Glycogen storage disease; Liver glycogenosis; Phosphorylase kinase deficiency; X-linked