Case series of monogenic diabetes due to HNF1B mutation

Ayman Elhomoudi; V Tziaferi; James Greening; Prem Sundaram

doi:10.1530/endoabs.58.P075

Introduction: A case series of three children diagnosed with MODY at a university hospital between November 2015 and May 2018. All of them was found to have HNF1B mutation.

Background: HNF1β-MODY (MODY5) is a rare form of monogenic diabetes that is often associated with a wide range of urinary tract anomalies including renal cysts. It’s a dominantly inherited disease including maturity-onset diabetes of the young (MODY), pancreatic insufficiency and some psychological disorders. Clinical presentation of renal cyst and diabetes syndrome (RCAD) includes renal involvement, deranged liver function, hyperuricemia and early-onset gout and reproductive tract abnormalities. In this case series report, we describe 3 cases of atypical non-autoimmune diabetes associated with a confirmed HNF1β mutation.

Management: Two children needed insulin for their diabetes management. Emphasis should be on lifestyle modifications such as weight loss and diet control. All three cases and their families had extensive genetic counseling and advise.

Conclusion: In our case series, we have shown that early diagnosis of HNF1B disease in childhood can help in early detection and management of diabetes and other co-morbidities. Co-morbidities include electrolytes imbalance, liver enzymes derangement, exocrine pancreas insufficiency and Psychological disorders were detected in case one and three. Molecular diagnosis has huge implications for the counselling and treatment of the patients and their family members.

Clinical presentations: See Table 1.

Table 1
	Case 1	Case 2	Case 3
Age at diagnosis (years)/sex	15/Male	13/Male	12/Male
BMI at diagnosis kg/m² (SDS)	33 (2.96)	18.4 (0.06)	34 (3.35)
HbA1c at diagnosis (mmol/mol)	117 (12.8%)	55 (7.1%)	52 (6.9%)
Initial treatment	MDI regime	Gliclazide	Metformin
Renal scan findings	Normal	Echogenic kidneys and single cyst	Single renal cyst
MODY genetics	HNF1B whole gene deletion	Chromosome 17q12 micro-deletion including HNF1B gene deletion	HNF1B c.884G>A
Other morbidities	Depression, ASD, ADHD	Exocrine pancreas insufficiency	Depression
Present treatment	MDI insulin+ Metformin	Insulin BD regime	Metformin
Family history	Type 2 diabetes	Mother and half-sister have same mutation	Mother type1, grandmother type2
Recent HbA1c (mmol/mol)	42 (6%)	51 (6.8%)	42 (6%)
Diabetes antibodies	Negative	Anti-GAD antibody 28	Negative

Endocrine Abstracts

P075