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Review
. 2025 Jul 4;19(1):317.
doi: 10.1186/s13256-025-05383-z.

A novel sequence of the PHKG2 mutation associated with the first case of glycogen storage diseases type IXc in Syria: a case report and review of literature

Seba Harh  1 , Shaza Shahoud  2 , Shady Daher  2 , Diana Alasmar  3
Affiliations
Review

A novel sequence of the PHKG2 mutation associated with the first case of glycogen storage diseases type IXc in Syria: a case report and review of literature

Seba Harh et al. J Med Case Rep. .

Abstract

Background: Glycogen storage diseases are a group of inherited metabolic disorders that affect the body's ability to break down and/or store glycogen. Type IX glycogen storage disease is an inherited disorder caused by a deficiency of phosphorylase kinase, which leads to various symptoms. We report the first reported case in Syria of glycogen storage disease type IXc caused by a novel phosphorylase B kinase catalytic subunit gamma 2 gene mutation, emphasizing the importance of early diagnosis and genetic counseling.

Case presentation: A 6-month-old Syrian male infant of Arab ethnicity presented with developmental delay, hepatomegaly, and hypoglycemia. Genetic testing identified a previously unreported phosphorylase B kinase catalytic subunit gamma 2 variant (c.801G > A p.( =)), classified as a variant of uncertain significance. Liver biopsy and clinical features were consistent with glycogen storage disease type IXc.

Discussion: This report expands the current understanding of phosphorylase B kinase catalytic subunit gamma 2-related glycogen storage disease type IXc by documenting a novel synonymous mutation with potential clinical significance. It underscores the critical role of early genetic testing in consanguineous populations, not only for accurate diagnosis but also for guiding family counseling and long-term management.

Conclusion: The identification of this novel mutation contributes to expanding the known phosphorylase B kinase catalytic subunit gamma 2 mutation spectrum and stresses the need for genetic counseling in similar populations.

Keywords: PHKG2 gene; Case report; Cornstarch therapy; Fasting hypoglycemia; GSD IXc; Glycogen storage diseases type IXc; Hepatomegaly; Novel mutation.

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Conflict of interest statement

Declarations. Ethics approval and consent to participate: We have clarified the ethical considerations. Ethical approval was not required for this case report as it does not involve any experimental procedures or interventions on human subjects outside of standard medical care. This determination was waived by the Ethics Committee of Damascus University Faculty of Medicine. Written informed consent for participation in this case report was obtained from the patient’s legal guardian. Consent for publication: Written informed consent was obtained from the patient’s legal guardian for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal. Competing interests: The authors declare that there are no competing interests.

References

    1. Li C, Huang L, Tian L, Chen J, Li S, Yang Z. PHKG2 mutation spectrum in glycogen storage disease type IXc: a case report and review of the literature. J Pediatr Endocrinol Metab. 2018;31(3):331–8. - PubMed
    1. Kim TH, Kim KY, Kim MJ, Seong MW, Park SS, Moon JS, et al. Molecular diagnosis of glycogen storage disease type IX using a glycogen storage disease gene panel. Eur J Med Genet. 2020;63(6):103921. - PubMed
    1. Kido J, Mitsubuchi H, Watanabe T, Sugawara K, Sasai H, Fukao T, et al. A female patient with GSD IXc developing multiple and recurrent hepatocellular carcinoma: a case report and literature review. Hum Genome Var. 2021;8(1):45. - PMC - PubMed
    1. Waheed N, Saeed A, Ijaz S, Fayyaz Z, Anjum MN, Zahoor Y, et al. Variability of clinical and biochemical phenotype in liver phosphorylase kinase deficiency with variants in the phosphorylase kinase (PHKG2) gene. J Pediatr Endocrinol Metab. 2020;33(9):1117–23. - PubMed
    1. Maichele AJ, Burwinkel B, Maire I, Sovik O, Kilimann MW. Mutations in the testis/liver isoform of the phosphorylase kinase gamma subunit (PHKG2) cause autosomal liver glycogenosis in the gsd rat and in humans. Nat Genet. 1996;14(3):337–40. - PubMed

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