Early Onset of Mody5 Due to Haploinsufficiency of HNF1B

Abstract

Objective: To report two patients with haploinsufficiency of HNF1B that results in the onset of MODY5 before three years of age. Methods: We present two unusual patients with MODY5 that was diagnosed at 33 and 22 months of age, respectively. We describe the presentations, clinical course and genetic tests of both patients, and lastly, we review the literature on the prevalence and the age of presentation of MODY5 both in children and in adult patients. Results: The first patient had severe congenital renal dysplasia, and DNA Microarray indicated the deletion of 17q12. HgbA1C was obtained due to the concern of MODY5, and the initial level (6.6%, 49 mmol/mol) was abnormally elevated. The second patient had mild renal dysplasia and 17q12 deletion encompassing the HNF1B gene. Hyperglycemia was identified during an episode of respiratory illness. HgbA1C (6.2%, 44 mmol/mol) level was abnormally elevated. Pancreatic autoantibodies were absent in both patients. Diet modification resulted in an improvement of HgbA1C in both patients. Conclusions: Our report highlights the importance of considering MODY5 in patients with congenital anomalies of kidney. Identification of children with MODY5 permits early management of hyperglycemia.

Maturity Onset Diabetes of the Young—New Approaches for Disease Modelling

“…In patients with HNF1B-MODY presence of cystic kidneys, pancreatic abnormalities and elevated liver enzymes are common and were used as predictors of HNF1B mutations [ 101 ]. Similarly, the presence of renal/pancreatic abnormalities in young patients with diabetes are suggestive for genetic testing for HNF1B-MODY [ 102 , 103 ].…”

17q12 Microdeletion Syndrome as a Rare Cause of Elevated Liver Enzymes: Case Report and Literature Review

“…Our patient has shown a structural renal anomaly which is a solitary right kidney with left renal agenesis that has been diagnosed during antenatal ultrasound screening. Structural and functional renal anomalies represent the most frequent cardinal presentation of the affected individuals with 17q12 recurrent deletion syndrome [1,2,6,7]. The congenital anomalies of kidneys and urinary tract (CAKUT) are associated with HNF1B mutation and include multicystic kidneys, renal dysplasia, renal hypoplasia, renal agenesis, hydronephrosis, hydroureter, pyelectasis, duplicated collecting system, vesicoureteric reflux and horseshoe kidney [2].…”

“…In addition to pancreatic structural anomalies, 17q12 deletion syndrome is also a common cause of MODY5 [7,9,10], which is an autosomal dominant type of monogenic diabetes [5]. The presentation onset of MODY5 is usually at the age between 13 and 25 years of age [3,7], but it may occur in any age group [1].…”

“…In addition to pancreatic structural anomalies, 17q12 deletion syndrome is also a common cause of MODY5 [7,9,10], which is an autosomal dominant type of monogenic diabetes [5]. The presentation onset of MODY5 is usually at the age between 13 and 25 years of age [3,7], but it may occur in any age group [1]. Bustamante et al have reported two cases where the patients presented early with MODY5 along with renal manifestations at the age of 22 and 33 months [7].…”

“…HNF1B gene belongs to the homeodomain-containing family of transcription factors whose mutation contributes to renal, hepatic, pancreatic, and urogenital tract disorders as it is involved in the organogenesis of the previously mentioned organs [2,5,6]. HNF1B gene mutation is a cause of MODY5 and renal abnormalities [2,5,7,8] that should be considered during screening for the disease or after the diagnosis is made, especially if there is renal involvement [7,9]. The LHX1 gene is responsible for early brain development and cognitive functions [8].…”