MODY-5 is caused by an autosomal dominant mutation in the HNF1b gene. Our objective is to report a case of a young female with a history of the dysplastic right kidney, diagnosed with gestational diabetes. Morphologic kidney abnormalities, electrolyte abnormalities (low magnesium and high urate), strong family history of diabetes, and renal abnormalities at young ages should alert the clinician of this diagnosis.
A previously healthy 22-year-old female was diagnosed with gestational diabetes after failing her 1-hour glucose tolerance test at 28 weeks gestation with a blood glucose level of 241. Elevated glucose levels were noted on random basic metabolic panels done prior to pregnancy, but the patient did not meet criteria to diagnose diabetes mellitus. Patient had no other symptoms at the time of the abnormal oral glucose tolerance test. The pertinent medical history prior to pregnancy included ultrasounds showing a small multicystic dysplastic right kidney. Patient’s left kidney showed compensatory hypertrophy and a small midpole cyst (Figure
Absent right kidney with compensatory hypertrophy noted in the left kidney.
Due to her diagnosis of gestational diabetes, prior elevated glucose readings, and pertinent medical history, a polycystic disease panel was performed to test for mature onset diabetes of the young (MODY). This panel came back positive for a pathologic mutation to HNF-1
Patient did experience other extrapancreatic symptoms that included low magnesium (1.3 mg/dl), high uric acid (11.1 mg/dl), and pancreatic hypoplasia noted on previous CT done two years prior to her diagnosis. CT scan was done to rule out renal stones and did show pancreatic tail hypoplasia (Figure
The uncinate process, head and body appear normal in size, but pancreatic tail is not visualized on noncontrast CT scan.
Pertinent labs done on the patient, showing low magnesium and high uric acid levels.
Lab | Value | Normal range |
---|---|---|
Fasting glucose | 113 mg/dl | <100 mg/dl |
C-peptide | 2.8 ng/ml | 0.9–7.1 ng/ml |
Magnesium | 1.3 mg/dl | 1.8–2.6 mg/dl |
Calcium | 9.9 mg/dl | 8.5–10.0 mg/dl |
Albumin | 4.5 mg/dl | 3.2–4.6 mg/dl |
Uric acid | 11.1 mg/dl | 2.9–6.3 mg/dl |
PTH | 70.1 pg/ml | 8.5–77 pg/ml |
Creatinine | 1.08 mg/dl | 0.60–1.05 mg/dl |
GFR | 73 ml/min/BSA | <60 ml/min/BSA |
Monogenic forms of diabetes result from a single gene defect with an autosomal dominant pattern of inheritance. A high index of suspicion based on the strong family history of diabetes at young ages in at least three generations is suggestive of this diagnosis which can affect successful patient management, ensure healthy pregnancy in female patients, and offering genetic counselling to the families.
To date, fourteen different genes have been implicated in the etiology of MODY. GCK mutation is the most common culprit mutation accounting for 30–50% of all MODY [
Although the exact prevalence is not known, current estimates suggest that 1–5% of all diabetes cases in the United States and other developed countries are a monogenic form of diabetes [
The first case of MODY-5 was reported in 1997 in a Japanese family [
HNF1B-associated MODY is a multisystem disease and includes genital tract malformation, abnormal liver function test, hypomagnesemia, and hyperuricemia associated early gout; neurological features such as autism spectrum disorders and cognitive impairment are also seen in MODY-5. Renal cysts are the most frequently detected feature of HNF-1
Patients with a strong family history of diabetes at young ages and renal morphologic abnormalities diagnosed at or soon after birth should be considered for the HNF1B screen.
Diabetes prevalence was 80% and that of renal malformations was 91% in HNF-1
Pancreatic hypoplasia with resulting beta-cell hypoplasia results in decreased insulin secretion and release, altered glucose-sensing, and increased hepatic insulin resistance which also play a major role in the development of diabetes. Severity of pancreatic hypoplasia determines the severity of hyperglycemia and possibility of ketoacidosis at initial presentation. Imaging of the pancreas is therefore helpful in MODY-5 patients. Nongenetic factors that affect insulin sensitivity (infection, puberty, pregnancy, and rarely obesity) can trigger diabetes onset and affect the severity of hyperglycemia in MODY but do not play a significant role in the development of MODY [
Renal functional decline is reported; a median yearly decrease in the estimated glomerular filtration rate (eGFR) of 2.45 ml/min/1.73 m2 was observed in a study of 27 adults with an HNF-1
MODY-5 should be considered a multisystem disorder and should be considered in the differential in young patients with renal malformations.
Another group of patients where screening for HNF-1
Maturity onset diabetes of young
Hepatocyte nuclear factor one beta
Oral glucose tolerance test
Glucokinase.
The authors declare that they have no conflicts of interest.