Ann Pediatr Endocrinol Metab.  2023 Jun;28(2):149-154. 10.6065/apem.2142188.094.

A case of maturity-onset diabetes of the young type 4 in Korea

• Park GM
• Lee S
• Seo JY
• Lim KI

• KMID: 2543297
• DOI: http://doi.org/10.6065/apem.2142188.094

Abstract

Maturity-onset diabetes of the young (MODY) is a rare, autosomal dominant disease characterized by non-ketogenic diabetes mellitus (DM). MODY type 4, caused by PDX1 mutation, is a very rare subtype of MODY, especially in Korea. We report a case of a 10-year-old, nonobese girl with a family history of type 2 DM. After diagnosis, the patient’s serum glucose level was well controlled using metformin monotherapy; however, the glycated hemoglobin level increased to 9.0% approximately 2 years after treatment. No obesity or lifestyle problems were observed, and serum fasting C-peptide level was within the normal range. Furthermore, no islet-related autoantibodies were detected. A genetic screening for MODY using a next-generation sequencing panel was performed, and a likely heterozygous pathogenic PDX1 mutation (p.Gly246ArgfsTer21) was identified. The PDX1 variant was not detected in her mother, implying that the mutation had arisen de novo in the proband. She was prescribed insulin degludec in addition to metformin therapy, which improved her hyperglycemia. This report presents a novel MODY type 4 phenotype and highlights the importance of genetic screening in patients with MODY characteristics.

Keyword

Maturity-onset diabetes of the young; MODY type 4

Figure

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  Fig. 1. Pedigree of diabetes mellitus in the case family. Black symbols indicate individuals with diabetes, and open symbols indicate nondiabetic individuals. The arrow indicates the proband. Two maternal uncles recently had been diagnosed with type 2 diabetes mellitus; however, her mother did not know their exact information. Genotype is indicated by N, normal sequence allele and M, mutant allele. Age at diagnosis of diabetes (A) and present age (B) are represented as A/B.

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  Fig. 2. Results of Sanger sequencing of exon 2 in the PDX1 gene of the proband and her mother. (A) Binary alignment map visualization of the variant in PDX1. A partial sequence of PDX1 NM_000209.3 is shown. The position of the PDX1 exon 2 mutation c.735dup (p.Gly246ArgfsTer21) is highlighted by the vertical purple bar. (B) Targeted-NGS sequence analysis identified a heterozygous variant c.735dup (p.Gly246ArgfsTer21) in PDX1, a duplication of adenosine at exon 2 in the proband. The c.735dup heterozygous mutation is indicated by the red arrow. The variant was absent in electropherograms from the mother. Confirmation of the NGS-detected variant by Sanger sequencing. NGS, next-generation sequencing.

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  Fig. 3. Changes in glycated hemoglobin (HbA1c) level in the proband over a four-year follow-up period.

Reference

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