Introduction: Hypoglycemia harbors a broad differential diagnosis but is most often thought of in relation to poorly controlled diabetes. Recently however, there is growing evidence that genetic mutations, in the setting of hyperinsulinemic hypoglycemia (HH), are more common than previously noted as the primary cause of symptomatic hypoglycemia. One of 16 known genetic mutations implicated in HH is the gene that codes for the enzyme glucokinase, which has an integral role in glucose metabolism. Case: We describe the case of a 36-year-old relatively healthy male presenting with acute on chronic spells of shakiness relieved by eating who, after thorough work up for metabolic, hormonal, and structural causes of hypoglycemia, was determined to carry a previously undiscovered mutation in glucokinase that was responsible for his symptoms. Of note, his four-year-old son had already been diagnosed with HH that was successfully controlled with diazoxide by this time. Genetic testing confirmed that the patient and his son, along with the patient's father, all carried the same GCK missense variant Tyr215Phe which has not yet been documented in the scientific literature. Discussion: The patient, his father, and his son all had markedly different presentations, in both disease severity and treatment response, despite carrying the same mutation. This clinical variability within families with HH has been described before, but the specific explanation for this finding, given the apparent autosomal dominant transmission, remains poorly understood and understudied. The roles of micro RNA, the immune system, tissue specific promoters, and other individual metabolic differences in people with HH have all been explored with this in mind. We also discuss the short-term physiologic response to hypoglycemia and analyze compensatory mechanisms that those with HH may harbor to endure longer durations of hypoglycemia. Conclusion: The discovery of the new variant in the GCK gene located on chromosome 7 in this case suggests that there are still undiscovered mutations responsible for HH. This case also highlights the need for further research characterizing the physiology, phenotypic variability, and natural history of the disease, particularly as its prevalence increases in the setting of more advanced diagnostic methods.
|Original language||English (US)|
|Journal||Journal of Clinical and Translational Endocrinology: Case Reports|
|State||Published - Jun 2021|
ASJC Scopus subject areas
- Endocrinology, Diabetes and Metabolism