Endocrine Abstracts

JOINT696

We present a 7-year-old black African girl with no significant past medical history. The patient presented to the acute paediatric assessment unit following a fall whilst running for the bus. In the preceding week, she experienced multiple falls, several of which occurred where she had fallen from standing still without identifiable cause. The falls were preceded by a 2-month history of abnormal gait and arm positioning. No prodrome occurred prior to the falls, with no recollection of the fall itself. She was not post-ictal and become responsive immediately after. She denied any recent coryzal illness or fever. There was no birth, personal or family history of note. At initial assessment, her weight was 39.3kg (>99.6^th centile), height 1.3m (>92.0^nd centile) and BMI 23.18kg/m² (99.7^th centile). She had a normal clinical examination, excluding difficulty performing heel-to-toe gait movements and left-sided dysdiadochokinesia. CT imaging of her head demonstrated symmetrical intra-axial calcifications predominantly involving subcortical white matter, basal ganglia and thalami. No evidence of intracranial haemorrhage or space-occupying lesions existed. Based on the distribution of calcifications, the imaging suggested a metabolic or genetic origin. X-ray of her hands showed normal contour and length of metacarpal bones. The appearance was within normal limits, with no bony exostosis or soft tissue calcifications. Laboratory investigations revealed significant hypocalcaemia, adjusted Ca²⁺ 1.43 mmol/l, high serum phosphate 3.25 nmol/l, low 25-hydroxy vitamin D 38 nmol/l and markedly elevated PTH 619 pmol/l. Further studies demonstrated a calcium:creatinine ratio of 0.04 and normal thyroid function. She responded to treatment with oral calcium, colecalciferol and alfacalcidol, with normalisation of bone biochemistry and resolution of gait/coordination deficits. Methylation-specific MLPA demonstrated almost complete loss of the maternal methylation pattern at all four differentially methylated regions (DMRs) of the GNAS locus. No deletion was detected within GNAS or STX16. These findings confirmed a diagnosis of pseudohypoparathyroidism (PHP) type 1b. Pseudohypoparathyroidism is a rare heterogeneous group of disorders characterised by end-organ resistance to parathyroid hormone (PTH), in which other hormonal deficiencies, such as hypothyroidism and hypogonadism, may coexist. In PHP-1b, defective methylation leads to impaired Gsα expression, causing renal resistance to PTH. The basal ganglia are the most common sites of CNS calcification in PHP. This case highlights a rare but important cause of CNS calcifications. Early diagnosis and genetic confirmation are crucial for effective management, precise family counselling, and identifying at-risk relatives for early intervention.