ESPE Abstracts (2018) 89 P-P1-055

Wolfram Syndrome Case with Hypergonadotropic Hypogonadism: A Novel Mutation

Zeynep Uzan Tatlıa, Gul Direka, Mervenur Hepokura, Nihal Hatipoglua, Leyla Akına, Mustafa Kendircia & Selim Kurtoglub


aErciyes Univercity of Medicine, Pediatric Endocrinology Clinic, Kayseri, Turkey; bMemorial Hospital, Pediatric Endocrinologist, Kayseri, Turkey


Introduction: A rare cause of diabetes mellitus is Wolfram Syndrome, which arises from mutations in wolframin gene found on chromosome 4. Optic nerve atrophy, diabetes insipidus, sensorineural deafness, psychiatric problems can accompany diabetes mellitus, so it can be also named as DIDMOAD syndrome. Hypergonadotrophic hypogonadism can be rarely observed in Wolfram syndrome. A case of novel homozygous mutation in the wolframin gene has been reported because of concomitant rarely reported hypergonadotropic hypogonadism.

Case: The patient admitted with complaints of drinking too much water and frequent urination at the age of 2.8 years. He was born at term with 3500gr and his parents were second-degree cousin. At the beginning patient’s blood sugar was 234 mg/dl and HbA1c was 10% with no metabolic acidosis. Insulin treatment was started immediately with the diagnosis of diabetes mellitus. Older sister of the patient had DIDMOAD syndrome. According to the history and examination, the diagnosis of Wolfram syndrome was considered. There was no optic nerve atrophy in the ophthalmic examination. Diabetes insipidus was not considered due to the normal values of urine density and serum sodium levels. The laboratory examination of the patient for Celiac and Hashimoto diseases was also normal. HbA1c values of the patient being followed for many years with insulin therapy are shown in graph 1. Optic atrophy was detected for the first time when the patient was 10.4 years old. Neither diabetes insipidus nor deafness has been observed so far. Pubertal development of the patient was compatible with Tanner stage 2 when he was 12.8 years old. In follow-up, it was observed that the testicle volumes increased by 10ml, but did not show any progress. Laboratory examination suggested hypergonadotropic hypogonadism with serum levels of LH (luteinizing hormone): 20.9 mIU/ml, FSH (follicle-stimulating hormone): 49.9 mIU/ml ve Total Testosterone: 347 ng/dl. Intramuscular testosterone treatment was initiated after azoospermia was detected in the spermiogram and gradually decreased testosterone levels. Genetic examination revealed a homozygous mutation of c.2069G> A/p(Cys690Tyr) in the wolframine gene, which was not previously reported.

Conclusion: DIDMOAD syndrome should be considered in patients who are diagnosed with antibody-negative diabetes mellitus. It is well known that diabetes insipidus and optic atrophy may develop in the follow-up of these patients, but it should be kept in mind that rarely hypergonadotropic hypogonadism may also accompany Wolfram syndrome as seen in our case.

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