Permanent neonatal diabetes mellitus: an important reason for genetic study

Neonatal Diabetes Mellitus is a rare type of Diabetes Mellitus. Moreover, when hyperglycemia begins before the age of 6 months and lasts for more than 14 days, it is considered as neonatal diabetes. The prevalence of this type of diabetes is about 1 in 500,000 live births.Overally, neonatal diabetes is categorized into two groups. In the transient form, the patients’ hyperglycemia is spontaneously improved. In the other type, the patients’ hyperglycemia is permanent and is called Permanent Neonatal Diabetes Mellitus (PNDM). One of the most prevalent causes of PNDM is activating mutation in KCNJ11 and ABCC8 genes which encode Kir6.2 subunit of the sensitive potassium (KATP) channel. Overall, oral hypoglycemic agent sulfonylurea is used in order to treat the PNDM patients with KCNJ11 gene mutation and in fact, the treatment is switched from Insulin therapy to sulfonylurea. A 28-day-old newborn is introduced who had presented with neonatal diabetes. After Insulin therapy, analysis of KCNJ11 gene was performed for the patient and after diagnosis of the mutation in this gene at the age of 2 months, the treatment was switched from Insulin to glibenclamide. After switching the treatment method to glibenclamide, the patient showed desirable glycemic control during the follow-ups.The case was a 28-day-old male newborn who had been referred to Namazi Hospital, Shiraz, Iran 7 days before the admission due to poor feeding, restlessness. He was born through the cesarean section by a 28-year-old mother with the gestational age of 36 weeks, birth weight of 2450 g, and good APGAR. The mother had undergone the cesarean section because of hypertension. The parents had non-consanguineous marriage and no history of special diseases such as diabetes was there in the family. He had desirable health status up to 1 week prior to the admission. Then, he presented with poor feeding, restlessness, and was referred to the hospital. In the physical examination, the patient seemed dehydrated and lethargic. Weight, length, and head circumference of the patient were 2800 gr, 48 cm, and 35.5 cm, respectively and the rest of the physical examinations were normal. Moreover, the patient’s laboratory findings revealed BS = 410 mg/dl, BUN = 25 mg/dl, Na = 140 mEq/lit, K = 3.9 mEq/lit, pH =7.32, Hco3 = 18, Pco2 = 24, calcium=9.2 mg/dl, CRP and blood culture negative.The patient’s treatment was started with intravenous fluid followed by Insulin. During the hospital stay. After recovery from the acute phase of the disease, since the patient had permanent hyperglycemia, NPH Insulin was started for him and finally he was discharged with 2 units NPH Insulin in the morning and 1 unit in the evening.Afterwards, blood sample was obtained from the patient and sent to the laboratory for genetic study. Analysis of KCNJ11 gene was performed for the patient and after diagnosis of the mutation in this gene at the age of 2 months and after one month treatment with Insulin, the treatment was switched from Insulin to glibenclamide. At first, 0.1 mg/kg/day glibenclamide was given to the patient in the morning and at night. Then, based on the blood sugar level, glibenclamide was increased to 0.6 mg/kg/day. After the treatment with glibenclamide, the patient’s hyperglycemia was successfully controlled and he did not need Insulin anymore. Now, the case is a 6-month-old infant with controlled hyperglycemia who only receives glibenclamide. Therefore, genetic study is recommended for KCNJ11 gene mutation in such patients because if the mutation is found, treatment can be switched from insulin to sulfonylurea. Although PNDM is a rare form of diabetes, it is important because KCNJ11 gene mutation can be identified as a common cause of PNDM in half of such patients. Furthermore, genetic study and finding this mutation is important since it helps the physician to change the patient’s treatment from Insulin to sulfonylurea.