グリコーゲン貯蔵病IX型：欧州3カ国の52例の長期追跡調査

Glycogen storage disease type IX (GSD IX) arises from hepatic phosphorylase b kinase (PhK) deficiency attributable to pathogenic variants in the PHKA2, PHKB, and PHKG2 genes. This multicenter retrospective study evaluated clinical and biochemical data from 52 patients diagnosed across three European countries, with a median follow-up of 9.3 years (range: 1-49). In the cohort, 86.5% were classified as GSD IXa, whereas GSD IXb and IXc accounted for 7.7% and 3.8%, respectively; one diagnosis was based solely on enzymatic testing. Null variants in PHKA2 consistently resulted in severe PhK deficiency, whereas missense variants and in-frame deletions were associated with variable enzymatic impairment (8/19 tested cases). The median age at symptom onset was 1.6 years, and the mean age at diagnosis was 2.0 years. Predominant manifestations included hepatomegaly (82%), elevated aminotransferases (81%), hypertriglyceridemia (71%), hypercholesterolemia (67%), hypoglycemia (46%), hyperlactatemia (38%), and short stature (30%). Aberrant apolipoprotein C-III glycosylation was detected in 80% of analyzed samples. Nutritional intervention was associated with improved growth (height SD score - 0.8 ± 1.3 vs -0.2 ± 1.65; p = 0.031) and fewer documented fasting hypoglycemia episodes (20/44 vs 9/44; p = 0.012), although hepatomegaly frequently persisted. Liver biopsies showed steatosis, fibrosis, and/or chronic hepatitis in 52% of examined cases. A single hepatic adenoma was identified in a 14-year-old male. Overall, the clinical course of GSD IX was favorable, with hepatomegaly, elevated liver enzymes, and dyslipidemia as the most prevalent features. Severe hypoglycemic episodes were uncommon, and no clear genotype-phenotype correlation emerged.