Introduction: Pseudohypoparathyroidism (PHP) is a rare disease, characterized by parathyroid hormone (PTH) resistance and it refers to different mineral disorders of bone metabolism, classified as PHP type 1a (Albright-OHA Hereditary Osteodystrophy), PHP1b and PHP1c (OHA).
Four cases reports: Four children were identified as having PHP, being three of them female. PHP was diagnosed at six years of age (three cases) and at seven years (one case). All children had diagnosis of hypothyroidism and one of them also had type 1 diabetes (T1DM) diagnosed at 12 years of age (six years after PHP diagnosis). One subject presented a mother with OHA phenotype, but normal laboratory assessment, characterizing pseudopseudohypoparathyroidism (PPHP). Different clinical manifestations were observed in the cases as craniofacial dysmorphisms (rounded facies, prominent forehead, flat nose...), brachydactyly, short neck, mild mental retardation, subcutaneous calcifications, short stature and obesity. Radiologic findings evidenced shortening of III, IV, and V metacarpals, epiphyses anomalies, lytic lesions andheterotopic ossification, suggestive of OHA. At diagnosis, all cases had elevated levels of PTH (Case 1: 807.3 pg/mL; 2: 281 pg/mL; 3: 111.5pg/mL and 4: 132 pg/mL reference value [RV] 15-65pg/mL), hypocalcemia (1: 9.0 mg/dL, 2: 7.3 mg/dL, 3: 9.8 mg/dL and 4: 8.1 mg/dL) was observed in three cases (RV: 8.2-10.3mg/dL) and hyperphosphataemia (1: 6.8 mg/dL, 2: 9.4 mg/dL, 3: 5.4 mg/dL and 4: 6.4 mg/dL) in only one case (RV: 4,0-7,0mg/dL). All cases were treated with calcitriol with or without oral calcium supplementation and molecular analysis was yet not available.
Discussion: PHP is characterized by renal defect in response to PTH, with hyperphosphatemia and elevated PTH, usually preceding hypocalcemia, being more commonly diagnosed during childhood. Genetically, PHP is caused by mutations in the gene that encodes the alpha subunit of G protein (GNAS), PTH action signaling protein, thyroid stimulating hormone(TSH), gonadotrophins andadrenocorticotropic hormone(ACTH) and others. The cases described in this series were all diagnosed in childhood and presented clinical and radiological manifestations suggestive of OHA.
19 - 21 Sep 2019
European Society for Paediatric Endocrinology