P0894 - Persistent Hypoglycemia with Polycystic Kidneys – A Rare Combination

A one-week old female infant was transferred to the NICU from an outlying hospital for concerns of persistent hypoglycemia, despite glucose boluses and parenteral glucose infusion. The patient was born at 39 weeks to a 25-year-old primigravida mother by spontaneous vaginal delivery. Pregnancy was uncomplicated, and negative for maternal diabetes. Mother’s prenatal labs, and ultrasounds during pregnancy showed no abnormalities. Mother was GBS positive for which she did not receive adequate therapy. Patient’s birth weight was 4119 grams (>90th percentile). Blood culture at the outlying facility was negative. Patient exhibited no fever or other issues while at the outlying hospital aside from the persistent hypoglycemia.
Upon admission to our NICU the patient was found to have a glucose level of 31 mg/dL requiring a 10% dextrose in water bolus of 2mL/kg. Intravenous glucose infusion was started at a rate of 10 mg/kg/minute that was later increased to 15 mg/kg/minute to maintain glucose levels above 40 mg/dL. Insulin and c-peptide levels were 19.6 uIU/mL (normal 2.6-24.9), and 4.1 ng/mL (normal 1.1-4.4), respectively on the initial episode of hypoglycemia. Diazoxide 10 mg/kg/24 hours divided into three doses was begun at two weeks of life. Glucose infusion was weaned after bolus feeds with 20 kcal/oz formula were initiated. The volume of feeding was increased gradually while parenteral fluids were weaned. Pre-prandial point-of-care blood glucose levels remained >50 mg/dL.

Hospital Course
Patient was weaned off Diazoxide, but after 24 hours of discontinuation the patient developed multiple episodes of hypoglycemia and Diazoxide was restarted. Repeat insulin levels during episodes of hypoglycemia remained at a high-normal.
Physical examination was concerning for bilateral renal enlargement. Abdominal ultrasound confirmed bilateral polycystic kidneys (figure 1), consistent with autosomal recessive polycystic kidney disease (ARPKD). Pancreas was not visualized, and liver showed no abnormalities. Both renal and liver function tests were within normal limits for age.
The patient was discharged at 3 weeks of life on full oral feeds, and Diazoxide to be continued on an outpatient basis. Given the findings of hyperinsulinemic hypoglycemia and polycystic kidney disease the patient was to follow with endocrinology, nephrology, and genetics. Molecular genetics testing revealed the patient to be heterozygous in the phophomannomutase 2 (PMM2) gene, with a mutation in the coding region (c.433G>A), and another in the promotor region (c.-167G>T). Repeat abdominal ultrasound after 3 months revealed renal cortical cysts bilaterally and scattered cysts in the liver (figure 2).

Discussion
The co-occurrence of two rare diseases, ARPKD and congenital hyperinsulinemic hypoglycemia (HI), suggests the existence of a different Mendelian disorder. We present, from our knowledge, the first case in the United States of a patient with Hyperinsulinemic Hypoglycemia with Polycystic Kidney Disease due to a PMM2 mutation in the promotor gene.