Endocrine Abstracts

JOINT2527

Background: Sanjad-Sakati Syndrome (SSS) is a rare autosomal recessive disorder predominantly reported in individuals of Arab descent. The hallmark endocrinological feature of SSS is primary hypoparathyroidism.

Aim: To define the clinical phenotypes and common complications of SSS in a Kuwaiti cohort.

Subjects and methods: This retrospective study included 17 patients from 14 families with SSS who were diagnosed, treated, or referred for follow-up at our center between 2005 and 2024. Their data were collected and analyzed.

Results: Seventeen patients (10 females, 59%) were recruited with median age of 10.7 years. Consanguinity was present in 9/14 families (64%). All patients were homozygous for TBCE founder mutation (c.155_166del; p. Ser52-Gly55del). One patient was additionally homozygous for the c.157+8A>T splice-site variant in intron 2 of ABCD4 gene, associated with methylmalonic aciduria and homocystinuria- an association not previously reported with SSS. The mean age of presentation was 34 days, primarily due to symptomatic hypocalcaemia. The main referral reasons were neonatal seizures (10/17), apnea (2/17) and poor activity (3/17). Dysmorphic features were present in all patients, including deep seated eyes, low set ears and peaked nose. Hypomagnesemia was observed in 24%, and 59% developed bilateral medullary nephrocalcinosis (median age: 3.5 years), with one of them progressing to end stage renal disease. All patients have hypoparathyroidism, while 18% have autoimmune hypothyroidism, 18% have adrenal insufficiency, and 41% experienced delayed puberty. Additionally, one patient has autoimmune hyperthyroidism, and one has growth hormone deficiency. Gastrointestinal manifestations included gastroesophageal reflux disease (41%), chronic constipation (18%) and recurrent intestinal obstruction (18%). Immune dysfunction was observed in 18%, characterized by reduced CD4 counts and low antibody response to vaccines. Ophthalmologic abnormalities were noted in 35%, including refractive errors and corneal opacity in one patient. Bilateral basal ganglia calcifications were present in 29%, with epilepsy diagnosed in two patients. MRI brain findings in three patients revealed corpus callosum and white matter volume loss with small pituitary gland. Nocturnal ventilatory support with bi-level positive airway pressure was required in 35% of patients. The mortality rate was 18% with septic shock as the leading cause of death.

Conclusion: SSS is a rare multisystem genetic disorder with significant morbidity and mortality. The novel association with ABCD4-related methylmalonic aciduria and homocystinuria expands the genetic and phenotypic spectrum of the disease. Given the high burden of complications, early diagnosis, multidisciplinary management, and vigilant long-term follow up are essential for optimizing patient outcomes.