HNF1B Mutation Misdiagnosed as Polycystic Kidney Disease

Introduction: HNF1b-related kidney disease, also known as autosomal dominant tubulointerstitial kidney disease (ADTKD) with renal cysts, is a rare genetic disorder caused by mutations in the HNF1b gene. It is characterized by the development of kidney cysts, tubulointerstitial fibrosis, and progressive renal dysfunction, and extrarenal manifestations that can be found in these patients are pancreatic failure, transaminitis, and genital tract abnormalities. Patients often present with features similar to Polycystic Kidney Disease (PKD), including hypertension, proteinuria, and renal insufficiency. Case Description: A 40 year old woman was evaluated by a Nephrologist after being informed that she had PKD based on magnetic resonance imaging. These images were captured during her pregnancy, for which she was noted to have fetal loss due to unknown causes. Pertinent laboratory results were random blood glucose level of 734 mg/dL, glycated hemoglobin 13%, erythrocyte sedimentation rate level was elevated at 26 mm/hr, urinalysis showed ketone bodies and sugar >1000 mg/dL. The results showed that her fasting glucose level was 398 mg/dL and serum C-peptide was 0.78 ngl/mL. Serum creatinine and eGFR were 0.6 mg/dL and 110, respectively. She was informed during a pregnancy that the fetus was presumed to have autosomal dominant PKD as evidenced by several small cysts in the maternal kidneys on magnetic resonance imaging. There was also a previous ultrasound that indicated a large cyst. Patient denied any family history of PKD. Patient reported that she was diagnosed with type 1 diabetes mellitus, which was misdiagnosed. It was deemed that the patient has Maturity-onset diabetes of the young, type 5 (MODY-5) due to testing negative for Anti-GAD, anti-IAA and anti-ICA antibodies, which is unique to type 1 diabetes. Discussion: Considering the patient had a cyst in the left kidney, negative for diabetes related antibodies, bicornuate uterus, pancreatic insufficiency, the patient was presumed to have MODY5 with the HNF1B score of 20. Upon further investigation to establish a working diagnosis, DNA sequencing revealed whole gene deletion of 17q12 deletion consistent with HNF1B mutation. Genetic testing plays a role in identifying specific mutations that can guide clinical management and counseling, particularly in cases where invasive procedures such as kidney biopsies are contraindicated, such as in pregnant individuals.