Endocrine Abstracts

Introduction: Glycogen Storage Disease Type VI (GSD VI), typically diagnosed in childhood, is rarely identified in adults. This case highlights a 48-year-old woman with adult-onset non-diabetic hypoglycemia, who was ultimately diagnosed with GSD VI.

Case Description: A 48-year-old woman presented with a ten-year history of intermittent, episodic symptoms including overnight sweating, cramps, morning fatigue, mood swings, and worsening migraines. Initial investigations in primary care failed to identify a cause. Hypoglycemia was confirmed using a Libre sensor, revealing primarily nocturnal and fasting episodes, unrelated to food timing or type. The patient had no significant weight changes and denied alcohol or tobacco use. Her medical history included migraines, managed with naproxen and sumatriptan. She had no history of gastric surgery, diabetes, or a family history of similar conditions. Extensive testing at our clinic included normal HbA1c, 9 am cortisol level, kidney and liver functions, and pituitary profile. Sulfonylurea screening was negative. C-peptide and insulin responses during a prolonged fasting test were appropriate, and the IGF-2:IGF-1 ratio was normal. Further fasting tests revealed elevated free fatty acids, beta-hydroxybutyrate, and some urinary organic acids, with normal carnitine and CK levels. Imaging studies, including a CT abdomen and pelvis (CTAP), were unremarkable. These findings excluded hyperinsulinemia-related causes such as insulinoma and pointed towards a possible metabolic cause related to glycogen utilization. Our endocrine MDT recommended a workup for GSD. Despite no pathogenic variant detected in genetic analysis for GSD, enzymatic analysis revealed abnormal kinetic activity in the glycogen phosphorylase enzyme, leading to a diagnosis of GSD VI (Hers disease).

Conclusion: This case underscores the complexity of diagnosing adult-onset non-diabetic hypoglycemia and highlights the importance of comprehensive metabolic evaluation and enzyme activity analysis in identifying the cause. The diagnosis in this patient suggests that mild variants of GSD VI may be underdiagnosed in the adult population.