Endocrine Abstracts

JOINT1101

Background: Albright hereditary osteodystrophy (AHO) is a rare genetic disorder caused by mutations in the stimulatory GTP-binding protein, Gαs, in the GNAS gene. It exists both with and without multihormone resistance-termed pseudohypoparathyroidism type 1A(PHP1A) and pseudo-pseudohypoparathyroidism(pseudo-PHP). AHO is characterized by obesity, short metacarpals, subcutaneous ossifications, round facies, varying degrees of cognitive impairments, and typically short adult stature.

Case Presentation: A 13-year-old female with the following complaints: retardation of psychomotor development, short stature, disturbance of gait, and pain in the joints admitted to the endocrinological department. She is the 2nd child of the family, was born at 38 months gestational age and antenatally was found to have deformity of the skull. In the 7th month, she was diagnosed with “Congenital hypothyroidism” with hypocalcemia and was prescribed Levothyroxine, which she takes up to this day. On physical examination: Height-114cm, weight-58kg, BMI-44.6kg/m², height SDS- - 7.05. The patient presents with developmental anomalies, including short stature and macrocephaly, with moon-shaped facies and a flat nasal bridge. The proximal segments of the upper limbs are shortened, accompanied by brachydactyly and positive metacarpal sign. The left lower extremity is shorter than the contralateral limb and there is evident hemihypertrophy and subcutaneous thickening is palpable in the area of the tarsal joint. The lower extremities are deformed, contributing to gait disturbances. The skin examination reveals numerous hyperpigmented macules distributed over the face and body, resembling dark moles. Since the age of 3, she has had focal seizures, 1-2 times a year, and is under the supervision of a neurologist, Carbamazepine was prescribed, which later was switched to Letiram. For hypocalcemia, she takes oral calcium daily, now 3000 mg. She also takes Calcitriol 2 tablets daily (since 10 years of age), and Vitamin D3 5000 IU daily. As the patient’s complex presentation including phenotypic overlap, hormonal and metabolic abnormalities, multisystem involvement, and seizures requires multidisciplinary involvement, in 2022, a medical genetic consultation was performed followed by whole genome sequencing, which confirmed GNAS gene mutation likely PHP or pseudo-PHP.

Conclusions: This case highlights the diagnostic complexity of a patient with a rare genetic disorder, multiple developmental anomalies, endocrinopathies, and neurological symptoms. The overlapping phenotypic features and systemic involvement underscore the importance of a multidisciplinary approach to diagnosis and management.