ESPE Abstracts

Background: Woodhouse-Sakati syndrome (WSS) is a rare, autosomal recessive genetic disorder with variable clinical manifestations mainly affecting the endocrine and nervous systems. Diabetes mellitus is one endocrine manifestation but there are no comprehensive data on the epidemiology, clinical features, underlying mechanisms, and management, particularly within the Qatari population.

Methods: This retrospective study was conducted at Sidra Medicine, Doha, Qatar, focusing on patients diagnosed with WSS. Data related to diabetes were collected for each patient. Additionally, a review of the literature was performed using the PubMed database and Google Scholar. Search keywords included "Woodhouse Sakati" in combination with "Diabetes," "Prediabetes," "Insulin," or specific genes associated with WSS, such as C2orf37 and DCAF17.

Results: We report findings from 18 Qatari patients diagnosed with WSS, comprising 8 females (44%) and 10 males (56%), with an average age of 17 years (range 9-23 years). Notably,11 patients (61%) were diagnosed with diabetes, with an average onset age of 16 years (range 12-22 years). At diagnosis, the average HbA1c was 9% (range 6.6-13%), accompanied by an average C-peptide level of 266 ng/ml and average insulin level of 96 pmol/l. Furthermore, 18% of diabetic patients tested positive for beta cell autoantibodies with average of one positive autoantibody in each patient (GAD antibody, ZNT8 antibody). Additionally, 36% of the diabetic patients presented with hypothyroidism, diagnosed at an average age of 13 years, characterized by negative thyroid peroxidase antibodies (TPO). None of the patients had celiac disease. Treatment modalities varied, with 55% of diabetic patients managed with a combination of insulin and oral medication (metformin and other types of oral medication in adult patients), while 45% were treated solely with oral medication. Moreover, 22% of the total patient cohort had prediabetes, with an average onset age of 11 years (range 9-14 years), and one-quarter of them tested positive for beta cell autoantibodies.

Conclusion: This study suggests that diabetes develops mostly around puberty in WSS patients and that some patients may test positive for beta cell autoantibodies. WSS patients should be monitored for the development of diabetes around pubertal age and these findings underscore the importance of early detection of diabetes in these patients. The molecular basis of the diabetes in WSS in unclear but might involve beta-cell exhaustion or damage. Understanding the mechanism of diabetes in these patients will help to develop management strategies.