Chromosome 6q24-related diabetes mellitus

• Published in: Clinical Pediatric Endocrinology Vol. 27; no. 2; pp. 59 - 65
• Main Authors: Yorifuji, Tohru, Higuchi, Shinji, Hosokawa, Yuki, Kawakita, Rie
• Format: Journal Article
• Language: English
• Published: Japan The Japanese Society for Pediatric Endocrinology 01.01.2018
• Subjects: 6q24; diabetes; imprinting; neonate; Review; neonate; imprinting; diabetes; 6q24
• ISSN: 0918-5739; 1347-7358
• DOI: 10.1297/cpe.27.59

Chromosome 6q24-related diabetes mellitus is the most common cause of transient neonatal diabetes (TNDM), accounting for approximately two-thirds of all TNDM cases. Patients with 6q24-TNDM develop insulin-requiring diabetes soon after birth, followed by the gradual improvement and eventual remission of the disorder by 18 mo of age. The most important clinical feature of affected patients is a small-for-gestational age (SGA) birth weight, which reflects the lack of insulin in utero. It is believed that 6q24-TNDM is caused by the overexpression of the paternal allele of the imprinted locus in chromosome 6q24, which contains only two expressed genes, PLAGL1 and HYMAI. Identified mechanisms include: (1) duplication of the paternal allele, (2) paternal uniparental disomy, and (3) hypomethylation of the maternal allele. Many patients with TNDM relapse after puberty. Relapsed 6q24-related diabetes is no longer transient and typically occurs in non-obese patients who are autoantibody negative. Thus, these patients possess features indistinguishable from those of maturity-onset diabetes of the young (MODY). Conversely, it has been shown that not all patients with 6q24-related diabetes have a history of TNDM. 6q24-related diabetes should therefore be considered as one of the differential diagnoses for patients with MODY-like diabetes, especially when they are SGA at birth.