Abnormalities in chromosome 6q24 as a cause of early‐onset, non‐obese, non‐autoimmune diabetes mellitus without history of neonatal diabetes

Abstract

Abnormalities in the imprinted locus on chromosome 6q24 do not necessarily cause transient neonatal diabetes. Non-penetrant 6q24-related diabetes could be an underestimated cause of early-onset, non-autoimmune diabetes in patients who are not obese and born small-for-gestational age.

ISPAD Clinical Practice Consensus Guidelines 2018: The diagnosis and management of monogenic diabetes in children and adolescents

“…Interestingly, some carrier relatives develop type 2 diabetes or gestational diabetes in adulthood without any evidence of having had NDM, as well as in a small fraction of patients with early‐onset, non‐obese, and non‐autoimmune diabetes without a history of NDM. This suggests significant variability in phenotype, possibly related to other genetic or epigenetic factors that may influence the clinical expression alterations of chromosome 6q24 …”

“…This suggests significant variability in phenotype, possibly related to other genetic or epigenetic factors that may influence the clinical expression alterations of chromosome 6q24. 36,56 The role of genetic counseling depends on the underlying molecular mechanism. Uniparental disomy of chromosome 6 is generally sporadic and therefore the risk of recurrence in siblings and offspring is low.…”

Permanent neonatal diabetes caused by abnormalities in chromosome 6q24

“…It has been reported that the loss of 6q24 methylation can also cause early-onset, non-obese, non-autoimmune diabetes mellitus; in this situation, being small for gestational age appears to be an essential marker [6,7]. It has been reported that the loss of 6q24 methylation can also cause early-onset, non-obese, non-autoimmune diabetes mellitus; in this situation, being small for gestational age appears to be an essential marker [6,7].…”

“…This case expands the clinical features of neonatal diabetes, especially 6q24 methylation defects. It has been reported that the loss of 6q24 methylation can also cause early-onset, non-obese, non-autoimmune diabetes mellitus; in this situation, being small for gestational age appears to be an essential marker [6,7]. Clinical hypoglycaemia was observed after diabetes remission in some people with 6q24 transient neonatal diabetes mellitus [8,9].…”

Congenital Diabetes: Comprehensive Genetic Testing Allows for Improved Diagnosis and Treatment of Diabetes and Other Associated Features

“…The hyperglycemia in these cases is often identified within the first few days of life and resolves spontaneously within the first year of life, but it returns later, usually around adolescence. However, two atypical cases of 6q24-related diabetes have recently been reported, including a case of permanent diabetes (still insulin-requiring at age 5.5 years) [5] and a case that did not have hyperglycemia during the infancy period [6]. Insulin is frequently used, although non-insulin therapies, particularly sulfonylureas, have been beneficial in some cases [7–9].…”