Hepatic Glycogen Storage Disease Type IX: Long-Term Outcomes in the UK From 89 Patients

Hepatic glycogen storage disease type IX (GSD IX) is due to a deficiency of phosphorylase kinase and is one of the most common types of GSD. We conducted a retrospective, observational cohort study on individuals with GSD IX from across the United Kingdom. We describe the natural history and long-term outcomes for 89 individuals with GSD IX with a median age of 16.4 years (range 4 months to 73 years). This included 60 patients with IXα2, 12 with IXβ and 13 with IXγ2. We report 49 novel alleles in PHKA2, PHKB and PHKG2. The median age at initial presentation was 2.5 years, with 82% (n = 68) presenting with hepatomegaly and 46% (n = 38) presenting with ketotic hypoglycaemia. Steatosis was reported in 71% (n = 12) who had a liver biopsy. The mean Z-score for height at initial presentation was -1.21, and this significantly improved over childhood. A spectrum of severity was seen in all subtypes, with some requiring more intensive dietary management after initial presentation and others requiring no formal dietary treatment at all. No patients developed adenomas or hepatocellular carcinomas, and 75% (n = 33) of adults were on no dietary therapy. Individuals with IXγ2 had a more severe disease course and had significantly worse biochemistry at initial presentation compared to other subtypes. They were diagnosed at a younger age and required more intensive dietary management across the lifespan. We believe that GSD IXγ2 is an ideal target for novel therapies. We recommend regular monitoring and multidisciplinary input in all patients with GSD IX and encourage more formal assessment of protein intake with each review.