PDX1-MODY and dorsal pancreatic agenesis: New phenotype of a rare disease
PDX1-MODY and dorsal pancreatic agenesis: New phenotype of a rare disease
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DOI：
10.1111/cge.13044
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发表时间：
2018-02-01
影响因子：
3.5
通讯作者：
Teles, M. G.
中科院分区：
文献类型：
--
作者：
Caetano, L. A.;Santana, L. S.;Teles, M. G.
青少年发病型糖尿病 (MODY) 4 型或 PDX1-MODY 是一种罕见的单基因糖尿病，由 PDX1 杂合变异引起。仅在新生儿糖尿病病例中报道了与 PDX1 相关的胰腺发育异常。在这里，我们描述了 2 名 PDX1-MODY 患者的背侧胰腺发育不全。先证者自 14 岁起就患有糖尿病，并在患糖尿病 38 年后通过低剂量基础胰岛素和可检测到的 C 肽水平维持定期血糖控制。怀疑诊断为MODY。靶向下一代测序鉴定出 PDX1 中的杂合变体：c.188delC/p。 Pro63Argfs*60。计算机断层扫描显示尾部胰腺发育不全。粪便弹性蛋白酶低表明外分泌功能不全。他的儿子患有葡萄糖耐量受损，表现出类似的胰腺发育不全，并具有相同的等位基因变异。这个巴西家庭的不寻常表现使得罕见疾病表型得以扩展，证明即使在出生后一年后诊断出的 PDX1 相关糖尿病病例中也有可能检测到胰腺畸形。这一发现可以改善 MODY4 患者的治疗，从而导致胰腺发育不全和外分泌功能障碍的早期研究。
Maturity-Onset Diabetes of the Young (MODY) type 4 or PDX1-MODY is a rare form of monogenic diabetes caused by heterozygous variants in PDX1. Pancreatic developmental anomalies related to PDX1 are reported only in neonatal diabetes cases. Here, we describe dorsal pancreatic agenesis in 2 patients with PDX1-MODY. The proband presented with diabetes since 14 years of age and maintained regular glycemic control with low doses of basal insulin and detectable C-peptide levels after 38 years with diabetes. A diagnosis of MODY was suspected. Targeted next-generation sequencing identified a heterozygous variant in PDX1: c.188delC/p. Pro63Argfs*60. Computed tomography revealed caudal pancreatic agenesis. Low fecal elastase indicated exocrine insufficiency. His son had impaired glucose tolerance, presented similar pancreatic agenesis, and harbored the same allelic variant. The unusual presentation in this Brazilian family enabled expansion upon a rare disease phenotype, demonstrating the possibility of detecting pancreatic malformation even in cases of PDX1-related diabetes diagnosed after the first year of life. This finding can improve the management of MODY4 patients, leading to precocious investigation of pancreatic dysgenesis and exocrine dysfunction.