Endocrine Abstracts

JOINT300

Background and Aim: MODY 12 (Maturity-Onset Diabetes of the Young, type 12) is a rare form of monogenic diabetes caused by mutations in the ABCC8 gene. The current report describes the case of a young patient diagnosed with Type 1 Diabetes, who experienced prolonged intervals of hyperglycemia alternating with episodes of hypoglycemia and vice versa. Further investigation through genetic testing identified a heterozygous (HG38, chr11:17394379C>T, c.4432G>A) mutation in exon 37 of the ABCC8 gene, leading to the p.(Gly1478Arg) variant. The aim of the report is to show the difficulties and uncertainty of the management and treatment of patients with such clinical presentations.

Case Presentation: A 13-year-old Caucasian male, presented to the Emergency Department, with complaints of polyuria, polydipsia, and nocturia last 30 days. He also reported a weight loss of about 10 kg, current weight was 57kg (SDS=+0,96). HbA1c was 8.2%, fasting glucose was 19mmol/l, C-peptide was 1.48ng/ml (normal=1.1-4.4), antidiabetic antibodies were negative. The patient was initially diagnosed with type 1 diabetes with ketosis and subcutaneous insulin-therapy started with total of 0.105 units/kg of rapid-acting insulin. During next several years he stopped insulin-therapy and initiated again 2-3 times per year due to ketosis. After approximately four years the patient began experiencing frequent episodes of hypoglycemia, with blood glucose levels dropping as low as 2.0mmol/l without insulin injections, alternating with periods of hyperglycemia. Continuous alternation between hyperglycemia and hypoglycemia, prompted a genetic test. Since opportunities for genetic testing are limited in our country, the patient underwent testing abroad, in Moscow. In the ABCC8 gene (NM_000352.6), a heterozygous variant HG38, chr11:17394379C>T, c.4432G>AHG38, chr11:17394379C>T, c.4432G>AHG38, chr11:17394379C>T, c.4432G>A was identified in exon 37, resulting in the amino acid substitution p.(Gly1478Arg)p.(Gly1478Arg)p.(Gly1478Arg), with a sequencing depth of 225x (rs72559715rs72559715rs72559715). This variant has been previously reported as pathogenic in patients with autosomal dominant congenital hyperinsulinism and autosoma ldominant ABCC8-associated diabetes (MODY 12) (PMID: 19475716, 30098243, 30977832, 32928245). Now, the patient is 21 years old and experiences hypoglycemic episodes approximately 7–8 times per year without receiving any specific treatment.

Discussion: Current case highlights the diagnostic and clinical challenges associated with rare conditions, particularly in countries like Armenia, where access to genetic testing is limited. On the other hand, due to the lack of precise guidelines for the treatment and management of such patients, they could be misdiagnosed with other types of diabetes and receive inappropriate management.