Scholarlink

Background <p>Pathogenic variants in the <i>HNF1B</i> gene cause a multi</p> <p>system disorder encompassing organ abnormalities—primarily affecting the kidneys and pancreas—as well as metabolic disturbances, collectively referred to as <i>HNF1B</i>-related disease. While maturity-onset diabetes of the young type 5 is a well-recognized manifestation, neonatal diabetes mellitus (NDM) associated with <i>HNF1B</i> is exceedingly rare, and has only been reported in patients harboring single nucleotide variants.</p> Case presentation <p>We describe two unrelated female children presenting with transient NDM caused by a complete <i>HNF1B</i> gene deletion. Both developed hyperglycemia within the first days of life requiring short-term insulin therapy, followed by spontaneous normalization of glycemia. However, their subsequent phenotypes diverged significantly. The first patient exhibited bilateral renal dysplasia while maintaining normal neurodevelopment. In contrast, the second patient developed later-onset cystic kidney disease, neurodevelopmental delay, and dysmorphic features, consistent with a broader 17q12 deletion syndrome spectrum. Although, in both cases, kidney abnormalities and extra-renal features (NDM, hypomagnesemia, hyperuricemia) were observed, both patients experienced a delay in diagnosis. On follow-up, serial oral glucose tolerance tests (OGTT), HbA1c assessments, and glucagon stimulation tests to date demonstrated preserved β-cell function, with the exception of hyperglycemia in 30–60 min of the extended OGTT in one patient.</p> Conclusions <p>These two cases represent the first report of transient NDM due to <i>HNF1B</i> deletion. Our findings broaden the molecular and clinical spectrum of <i>HNF1B</i>-related diabetes, and emphasize the importance of considering <i>HNF1B</i> defects in children with transient neonatal hyperglycemia.</p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

Transient neonatal diabetes mellitus as an early diagnostic clue to HNF1B-related disease – two case reports and a literature review

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年4月16日

查看全文
  • Marcin Kołbuc,
  • Paweł Bednarek,
  • Rafał Motyka,
  • Tomasz Jarmoliński,
  • Marzena Michalak-Kloc,
  • Bodo B. Beck,
  • Małgorzata Urbańska-Kosińska,
  • Marcin Zaniew

摘要

Background

Pathogenic variants in the HNF1B gene cause a multi

system disorder encompassing organ abnormalities—primarily affecting the kidneys and pancreas—as well as metabolic disturbances, collectively referred to as HNF1B-related disease. While maturity-onset diabetes of the young type 5 is a well-recognized manifestation, neonatal diabetes mellitus (NDM) associated with HNF1B is exceedingly rare, and has only been reported in patients harboring single nucleotide variants.

Case presentation

We describe two unrelated female children presenting with transient NDM caused by a complete HNF1B gene deletion. Both developed hyperglycemia within the first days of life requiring short-term insulin therapy, followed by spontaneous normalization of glycemia. However, their subsequent phenotypes diverged significantly. The first patient exhibited bilateral renal dysplasia while maintaining normal neurodevelopment. In contrast, the second patient developed later-onset cystic kidney disease, neurodevelopmental delay, and dysmorphic features, consistent with a broader 17q12 deletion syndrome spectrum. Although, in both cases, kidney abnormalities and extra-renal features (NDM, hypomagnesemia, hyperuricemia) were observed, both patients experienced a delay in diagnosis. On follow-up, serial oral glucose tolerance tests (OGTT), HbA1c assessments, and glucagon stimulation tests to date demonstrated preserved β-cell function, with the exception of hyperglycemia in 30–60 min of the extended OGTT in one patient.

Conclusions

These two cases represent the first report of transient NDM due to HNF1B deletion. Our findings broaden the molecular and clinical spectrum of HNF1B-related diabetes, and emphasize the importance of considering HNF1B defects in children with transient neonatal hyperglycemia.