An extremely rare case of glycogen storage disease type VI diagnosed on top of celiac disease in a 4.2-year-old girl

Abstract Glycogen storage disease type VI (GSD VI) (also known as Hers disease) caused by biallelic variants in the PYGL gene results in the deficiency of hepatic glycogen phosphorylase enzyme and commonly presents during early childhood. Celiac disease is a systemic immune-mediated disorder triggered by the ingestion of dietary gluten in genetically-predisposed individuals also presenting in early childhood. Herein, we report an extremely rare case of genetically confirmed GSD VI, diagnosed in association with celiac disease in a 4.2-year-old Libyan girl with non-consanguineous parents. To our knowledge, celiac disease has never been reported previously in association with GSD VI. The patient was initially diagnosed with celiac disease at the age of 3 years and showed partial improvement on a strict gluten-free diet. However, her abdominal distention persisted due to marked hepatomegaly and for this she was referred for consultation at Cairo University Children Hospital, Cairo, Egypt. A liver biopsy was subsequently performed at the age of 4.2 years and was consistent with the diagnosis of GSD. Whole exome sequencing confirmed the diagnosis of GSD VI through the detection of two heterozygous likely pathogenic PYGL variants: a previously reported NM_002863.5:c.1499T > G; p.(Leu500Arg), and a novel variant NM_002863.5:c.1736T > C; p.(Leu579Ser). The patient was promptly prescribed uncooked cornstarch alongside the continued gluten-free diet. At the age of 6 years, abdominal ultrasonography showed a 4.4 cm reduction in the liver size along the mid-clavicular line and improved laboratory studies. We came to the conclusion that in pediatric practice, a definitive diagnosis of one disease should not deter from searching for other disease(s) particularly if the symptoms and/or signs are not adequately explained.