Blood glucose trends in glycogen storage disease type Ia: A cross‐sectional study

Abstract

Background Glycogen storage disease type Ia (GSDIa) is caused by biallelic pathogenic variants in the glucose‐6‐phosphatase gene (G6PC) and mainly characterized by hypoglycemia, hepatomegaly, and renal insufficiency. Although its symptoms are reportedly mild in patients carrying the G6PC c.648G>T variant, the predominant variant in Japanese patients, details remain unclear. Therefore, we examined continuous glucose monitoring (CGM) data and daily nutritional intake to clarify their associations in Japanese patients with GSDIa with G6PC c.648G>T. Methods This cross‐sectional study enrolled 32 patients across 10 hospitals. CGM was performed for 14 days, and nutritional intake was recorded using electronic diaries. Patients were divided according to genotype (homozygous/compound heterozygous) and age. The durations of biochemical hypoglycemia and corresponding nutritional intake were analyzed. Multiple regression analysis was performed to identify factors associated with the duration of biochemical hypoglycemia. Results Data were analyzed for 30 patients. The mean daily duration of hypoglycemia (<4.0 mmol/L) in the homozygous group increased with age (2–11 years [N = 8]: 79.8 min; 12–18 years [5]: 84.8 min; ≥19 years [10]: 131.5 min). No severe hypoglycemic symptoms were recorded in the patients' diaries. The mean frequency of snack intake was approximately three times greater in patients aged 2–11 years (7.1 times/day) than in those aged 12–18 years (1.9 times/day) or ≥19 years (2.2 times/day). Total cholesterol and lactate were independently associated with the duration of biochemical hypoglycemia. Conclusion Although nutritional therapy prevents severe hypoglycemia in patients with GSDIa with G6PC c.648G>T, patients often experience asymptomatic hypoglycemia.

A splice-switching oligonucleotide treatment ameliorates glycogen storage disease type 1a in mice with G6PC c.648G>T

“…GSD1a was once a fatal disease in infancy due to severe hypoglycemia, but the life expectancy and prognosis have been substantially improved by introducing frequent (every 4–6 h) intake of a starch-rich diet against life-threatening hypoglycemia as a standard of care. Despite the heavy burden on patients and their families, this approach does not sufficiently prevent biochemical hypoglycemia, glycogen accumulation, or other metabolic abnormalities that lead to hepatocellular adenoma/carcinoma (HCA/HCC) and renal injury ( 3 – 8 ).…”