Hypoglycaemia following diabetes remission in patients with 6q24 methylation defects: expanding the clinical phenotype.
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ABSTRACT:
SUBMITTER: Flanagan SE
PROVIDER: S-EPMC3982857 | biostudies-literature | 2013 Jan
REPOSITORIES: biostudies-literature
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Hypoglycaemia following diabetes remission in patients with 6q24 methylation defects: expanding the clinical phenotype.
Flanagan S E SE Mackay D J G DJ Greeley S A W SA McDonald T J TJ Mericq V V Hassing J J Richmond E J EJ Martin W R WR Acerini C C Kaulfers A M AM Flynn D P DP Popovic J J Sperling M A MA Hussain K K Ellard S S Hattersley A T AT
Diabetologia 20121031 1
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Project description: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.
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Project description:BackgroundTransient neonatal diabetes mellitus (TNDM) is the most common cause of diabetes in the first week of life, with an overall incidence of 1 in 90,000 to 160,000 live births. TNDM occurs soon after birth and undergoes spontaneous remission during infancy; however, it may relapse to a permanent form of diabetes mellitus in childhood or adolescence. We report a case of TNDM due to hypomethylation on chromosome 6q24, associated with a rare clinical finding of nonsuppurative submandibular sialadenitis managed by subcutaneous insulin, and who underwent remission by three months of age. Case Presentation. We report a male neonate of Arab ancestry delivered by caesarean section at 37 weeks of gestation. He had intrauterine growth retardation with a birth weight of 2.099 kg. He presented with hyperglycemia on the first day of life, which was managed with parenteral insulin infusion. Blood glucose control was initially difficult to achieve due to difficulties in preparing such small doses of insulin and the significant variations in blood glucose concentrations, without ketosis. Blood tests revealed low serum insulin and C-peptide levels. Genetic analysis revealed multiple loci hypomethylation of the PLAGL1/HYMAI-DMR in the TNDM region in chromosome 6q24 and two pathogenic heterozygous variants in the ZFP57 gene. Segregation analysis showed that both parents were heterozygous carriers of familial ZFP57 variants. The clinical course was associated with bilateral nonsuppurative sialadenitis, which is extremely rare among newborns.ConclusionSialadenitis is a well-known phenomenon that is rarely diagnosed in neonates. To the best of our knowledge, this is the first case report to describe the exceedingly rare association of nonsuppurative submandibular sialadenitis in a neonate with TNDM due to multiple loci hypomethylation of the PLAGL1/HYMAI-DMR in the TNDM region in 6q24 and heterozygous pathogenic variants in the ZFP57 gene.
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