Case of Maturity Onset Diabetes of Young-Type V

Maturity Onset Diabetes of Young (MODY) is a rare cause of diabetes and accounts for 1-5% of cases and has an autosomal dominant mode of inheritance. Diagnostic criteria set forth for MODY include 1. Onset before 25 years of age in one family member 2. Presence of DM in two consecutive generations 3. Absence of β-cell autoantibodies 4. Sustained endogenous insulin secretion.

Case Description:

A male university student, aged 21 years, presented with uncontrolled DM. He was incidentally diagnosed with a case of T2D three years ago while undergoing pre-operative assessment for a right inguinal hernia repair and orchidopexy. He had a history of decreased shaving frequency (every 15 days) and no morning erections. There was a strong family history of DM, both from maternal and paternal sides.

He was obese with a BMI of 31.8 kg/m2 and had normal vital signs. On genital examination, the right testicle was undescended, while the left was present in the scrotum with normal size and consistency. There was no evidence of gynecomastia.

His first HbA1C from three years ago was 12.9% and subsequent levels were 6.4%, 10.0%, and 6.3%. C-peptide was normal (3.8 ng/ml), insulin level was also normal (13.0 mIU/L), and a high HOMA-IR of 3.21. His LH and FSH were 5.82 mIU/ml and 2.06 mIU/ml respectively. Serial testosterone levels were checked; showed fluctuating levels between 260.0 - 479.0 ng/dl. TSH and prolactin were normal; he also had hyperuricemia (7.8mg/dl) and hypomagnesemia (1.5 mg/dl). Liver function tests revealed raised ALT (51 U/L) and GGT (91U/L). His semen analysis was done twice and showed severe asthenospermia. His right testis measured 2.2x1.1cm, was located in the right inguinal canal, while the left scrotal testis was 4.1x3.1 cm, on ultrasound. It also showed distended epididymis and vas deferens. CT scan abdomen revealed fatty liver, normal kidneys but absent body and tail of pancreas representing partial agenesis of the pancreas. Genetic testing could not be done due to resource constraints.

Lifestyle Modification was advised along with sitagliptin, metformin, and glimepiride. He was referred to a urologist for removal of undescended testis and biopsy of scrotal testis. Counseling was done for fertility issues.

Discussion:

At diagnosis, MODY cannot be distinguished easily from T1D & T2D based on clinical characteristics alone. T1D mostly differs from MODY in terms of disease etiology, as the pathogenesis of MODY does not involve pancreatic β-cell autoimmunity. Patients usually maintain β-cell function, & their diabetes is well-controlled with no or low-dose insulin for at least 5 years after diagnosis, as in our case. To date, at least 14 different gene mutations are associated with MODY. Among them, HNF-1B (previously called MODY 5), is associated with developmental renal disease, especially cysts, genitourinary malformations, gout, and pancreatic insufficiency. Additionally, these patients can have elevated liver enzymes, hyperuricemia, and hypomagnesemia. On the basis of these features, a diagnosis of MODY 5 was made in our patient.