Introduction: 17q12 deletion syndrome is associated with an enlarging phenotype, the most frequent clinical findings being renal and genitourinary malformations, diabetes mellitus (β-cell developmental defect) and exocrine pancreas deficiency, variable cognitive impairment with dysmorphic features.
Diabetes, known as MODY 5 (maturity-onset diabetes of the young), is an autosomal dominant monogenic type and the most commonly identified mutation is an entire HNF1B gene deletion.
Many patients experience progressive deterioration of glucose homeostasis over time. Metformin could be the first-line drug, but early insulin therapy is required.
We present 2 brothers with maternally inherited 17q12 deletion including HNF1β.
Case presentation: At the age of 18 years, the patients' mother was diagnosed with type 1 diabetes (T1DM). By the age of 33, she had given birth to 3 dysmorphic children. The genetic analysis of the mother and children found a 1.4-Mb deletion in chromosome 17q12, including the HNF1β gene.
Patient 1 is an 11-year-old male child who presented with polyuria. His medical history included cognitive delay, hepatic cytolysis, and ophthalmic abnormalities with normal brain magnetic resonance imaging. He was overweight, with mild cognitive impairment, behavioral difficulties and dysmorphic features. The biological check-up revealed: hyperglycemia, glycosuria, without ketonuria, HbA1c 7%, preserved insulin secretion and negative autoimmune markers of T1DM. He also presented mild hyperuricemia and hepatic cytolysis. There were no renal or genitourinary abnormalities.
With a MODY 5/17q12 syndrome diagnosis, metformin was started with immediate good glycemic control. Fifteen months later, he developed a severe keto-acidosis and the treatment was changed; currently, he is under insulin 1.07 u/kg/d.
Patient 2 is a 14-year-old male child who presented with the same phenotypic and genotypic features as his younger brother. At diagnosis, he was asymptomatic, but obese.
His biological check-up revealed fasting glycaemia, HbA1c 6.8%, preserved insulin secretion, normal hepatic and renal function. He had no renal morphological abnormalities. Metformin was started; twelve months later, his HbA1c was 11.6%, and he had lost 4 kg. He is currently receiving insulin 0.32 u/kg/d.
Conclusion: MODY 5 diabetes treatment remains challenging.
Our cases showed similar phenotypes, with some biochemical differences. Their evolution was marked by early insulin requirement, maybe in a context of aggravating obesity, and different response to insulin therapy.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology