Ketotic hypoglycemia in patients with Down syndrome

Abstract

Background: Ketotic hypoglycemia (KH) without an identifiable underlying metabolic or hormonal disease is historically named idiopathic KH. The prevalence is unknown, but idiopathic KH is considered the most frequent cause of hypoglycemia beyond the neonatal period. KH in Down syndrome (DS) has not been reported. Methods:We conducted a web-based survey on KH in DS through the nonprofit patient organization Ketotic Hypoglycemia International. The responses were evaluated for consistency with KH by two authors. Two DS patient histories with documented KH were shared in more details. Results: Survey data on 139 DS patients were obtained. After validation, 10 patients (7.2%) had reported episodes of documented hypoglycemia, ketosis, and/or symptoms compatible with KH beyond the neonatal period. Glucose concentrations ranged 1.2-2.9 mmol/L; betahydroxybutyrate was up to 5.5 mmol/L during hypoglycemia. One girl had trisomy 21 with no response to i.m. glucagon also had a heterozygous Xp22.23 deletion including GYG2, which protein, glycogenin 2, is a substrate for glycogen synthase. Treatment with extended release cornstarch was effective.Conclusion: This is the first demonstration of a possible high prevalence of KH in DS. Even though this finding needs to be confirmed in other research settings, identification of KH in DS could have a dramatic impact, as simple treatments with cornstarch, protein and frequent meals may prevent KH attacks and, analogous to other conditions with KH, improve growth, stamina and prevent overeating and obesity. GYG2 deletion may contribute to KH in DS, resembling glycogen storage disease type 0.

Ketotic hypoglycemia in patients with Down syndrome: an example of extreme citizen science in biomedicine

“…glucagon also had a heterozygous Xp22.23 deletion including GYG2, which protein, glycogenin 2, is substrate for glycogen synthase. Treatment with extended-release cornstarch was effective [18].…”

Hypoglycemia Associated With PEG-asparaginase and 6-MP Therapy During Treatment of Acute Lymphoblastic Leukemia in Pediatric Patients: A Case Series

“…There also appears to be a higher prevalence of ketotic hypoglycemia in children with DS. 29 Given that an increased frequency of both ketotic and nonketotic hypoglycemia has been reported in children with DS, both within our study (associated with ALL therapy) and outside of our study, we believe that clinicians need to have a higher index of suspicion for the risk of hypoglycemia in children with DS with secondary risk factors for hypoglycemia (including ALL therapy) and that further study needs to be done to better understand the mechanism of both forms of hypoglycemia in this population.…”

Idiopathic ketotic hypoglycemia in children: an update

“…Furthermore, it was claimed that IKH is common in African children with chronic malnutrition or severe malaria [12,13]. Drachmann et al [14] found for the first time a high frequency of KH in 10 (7.2%) of 139 Down syndrome (DS) patients, with a median age of 8.0 years, in their study on the prevalence of KH in DS patients. Despite the fact that this result has to be verified in different study contexts.…”

“…This finding warranted verification in different study contexts. The authors suggested screening for KH in DS patients because it is possible to prevent KH attacks, enhance growth, and avoid overeating and obesity with simple therapies such as frequent meals, increased protein intake, and cornstarch consumption [ 14 ].…”