ESPE Abstracts

Background: Primary ovarian insufficiency (POI) manifests with delayed puberty, primary amenorrhea, and elevated levels of gonadotropins (LH, FSH). A variability in genetic factors in the origin of POI has been reported so far. Here we are reporting a case of POI with non-immune diabetes mellitus and mild intellectual disability suspected to have Woodhouse-Sakati Syndrome.

Case presentation: A 14 year and 4 months old adolescent female following in pediatric endocrinology clinic for delayed puberty. She is known to have mild intellectual disability with bad school performance and primary nocturnal enuresis. Parents are consanguineous (first cousin). By examination: she has subtle dysmorphic features, short for age (height: 142cm (-3.1 SD) with BMI:26 (+1.2SD). At the age of 15yr5mon she developed diabetes mellitus without DKA with absence of acanthosis nigricans. Investigations: HbA1C:8%, anti-GAD: negative consist with non-immune process, and for primary amenorrhea: karyotype was done XX, thyroid function test consist with autoimmune hypothyroidism, basal LH: 3.6U/L, FSH :23U/L. Pelvic US: uterine & ovaries could not visualized. Pelvic MRI: uterus is rudimentary, no ovaries seen. Bone age close to 14years. LHRH stimulation test showed LH level at 0, 20, 40, and 60 min:3.6, 13.6, 21.9, 24, and FSH: 33, 40,50, 58 respectively.

Discussion: Our patient diagnosed with primary ovarian failure based on the exaggerated response of LH and FSH to LHRH stimulation with the presence of delayed puberty. A recent diagnosis of non-immune diabetes mellitus with background of intellectual disability, mild alopecia mild defeaness, raised possibility of monogenic causes of DM. Genetic testing is done and showed homozygous pathogenic frameshift variant in her DCAF17 gene (NM_025000.4:c.436delC, p.(Ala147Hisfs*9). She was started on estrogen replacement therapy, along with metformin, then insulin therapy was added due to poor glucose control. segregation of parents and her brothers still pending.as had one brother 17.5yr old with dysarthria but normal puberty, and father had deafness with intelectual disability. After reviewing the family tree for similar condition, we found the daughter of maternal cousin was present with primary amenorrhea & with dm control on metformin with similar genetic mutation, so our case reflect the 3^rd case in Palestine diagnose with Woodhouse-Sakati.

Conclusion: Woodhouse–Sakati syndrome (WSS) is a rare multisystemic disease, with wide range of clinical features, and severity. Primary amenorrhea can be the presenting symptom caused by ovarian failure followed by other manifestations of DM, alopecia and neurological symptoms, so suspect this disorder in consanguineous family with hypogonadism & non-immune diabetes and intellectual disability. Also suspect any neurological manifestation in family member could be due to this genetic mutation.