PDX1‐MODY and dorsal pancreatic agenesis: New phenotype of a rare disease

Abstract

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.

Causal variants in Maturity Onset Diabetes of the Young (MODY) – A systematic review

“…Its symptoms may include overweight or obesity in some cases [ 19 ]. Dorsal pancreatic agenesis was reported with this MODY type [ 20 ].…”

Agenesis of the dorsal pancreas presenting with diabetic ketoacidosis – a case report and literature review

“…The pancreas develops from the ventral and dorsal buds, which fuse during the seventh week of gestation. The ventral bud gives rise to the uncinate process, post-inferior portion of the head, and Wirsung duct, whereas the dorsal bud, which drains into the minor papilla through the Santorini duct, gives rise to the upper head, body and tail [5]. Monogenic mutations in insulin promoter factor 1 [6], pancreas associated transcription factor 1 [7], and transcription factor-2 / hepatocyte nuclear factor-1 homeobox B [8] have been reported to associate with pancreatic agenesis, multigenic traits are likely to contribute to this disorder.…”

First Case Report of Maturity-Onset Diabetes of the Young Type 4 Pedigree in a Chinese Family

“…Pancreatic agenesis has only been reported in PDX1 mutated homozygosity (16) or compound heterozygosity (6). However, Caetano et al (17) recently described dorsal pancreatic agenesis in two Brazilian patients with MODY4, and one of them also had exocrine insufficiency. In our study, although no pancreatic agenesis was detected, the proband suffered from abdominal pain, and his serum lipase was slightly low, which characterizes exocrine pancreatic insufficiency.…”