Endocrine Abstracts

Introduction: Woodhouse-Sakati syndrome (WSS) is a rare autosomal recessive disorder characterized by diabetes, hypogonadism, hypothyroidism, sensorineural hearing loss, alopecia totalis, extrapyramidal findings and specific changes on ECG. This syndrome belongs to a heterogeneous group of neurodegenerative disorders and is caused by mutations of the DCAF17 gene. Treatment is symptomatic and patients are managed by multidisciplinary teams. About 90 cases were reported since 2008 when WSS was discovered.

Case report: We describe two sisters 18- and 29 years old affected by combined endocrine disorders such as diabetes, hypergonadotropic hypogonadism (with ultrasonic signs of uterine hypoplasia), hypothyroidism with negative thyroid auto antibodies, obesity and extrapyramidal symptoms such as dyslexia, sensorineural hearing loss, mild intellectual disability and dysmorphic facial features as well as alopecia totalis. GH, prolactin and ACTH levels were normal, but it should be noted that the younger sister had a low level of IGF. On ECG both of them had specific changes in the form of T-wave flattening. Brain MRI showed multiple brain cysts. Sisters differed in severity of clinical symptoms. The severity of the diabetic state is also varied between sisters. The younger sister had intact secretion of both basal and stimulated C-peptide levels, thus, she was prescribed sulfonylurea drugs with great glucose-lowering response. The older sister had a satisfactory basal and insufficient stimulated C-peptide levels, so she was switching to basis-bolus insulin therapy in conjunction with SGLT-2 inhibitors. They did not take levothyroxine and hormone replacement therapy with estrogen before. Common genetic, metabolic and mitochondrial disorders were excluded. WSS was suspected. Sequencing of DCAF17 gene detected new nucleotide variant NM_025000.3: c.1422 + 3G > T in homozygous state. This nucleotide variant has not been previously described.

Discussion: In the case of combinations of several endocrine pathologies with different characteristic features, genetic testing plays an important role. Thus, we can assume the progression of the disease as well as provide an integrated personalized approach to treatment. WSS was previously described in Arabian families and this is the first case in Russian family. Since we expect that diagnostic methodology and our understanding of disease pathology, including genes, allelic variants will improve in the future, DNA banking of affected individuals should be considered.