Background: Pseudohypoparathyroidism (PHP) is a rare group of disorders characterised by end-organ resistance to parathyroid hormone (PTH), and possibly TSH, with or without features of Albrights hereditary osteodystrophy.
Case presentation: A 14-year-old boy presented with fatigue and spontaneous carpal spasms in association with a febrile viral infection. Past medical history was significant for an episode of asymptomatic hypocalcemia treated with calcium and alphacalcidol. He had discontinued therapy and he was lost to follow-up. Family history was remarkable for episodes of hand numbness for the mother, muscle cramps for maternal grandfather and carpal spasms and multiple fractures for maternal great grand mother. Physical examination revealed an adolescent with no dysmorphic features, normal height and weight, fully pubertal, with no skeletal abnormalities except for mild genu valgum. He had positive Chvostek and Trousseau signs. Laboratory investigation revealed markedly low serum calcium (5.3 mg/dl), phosphate (5.6 mg/dl), while magnesium, albumin, ALP and TSH were normal. There were also markedly elevated PTH levels (299.4 pg/ml) and vitamin D deficiency (16.5 μg/lt). ECG showed prolonged corrected QT interval. The patient was initially treated with calcium and alphacalcidol. In summary, this patient presented with PTH resistance, and no phenotypic signs of Albrights osteodystrophy, normal puberty, thyroid function and cortisol production, consistent with the diagnosis of PHP-I. A molecular genetic analysis was performed that revealed loss of methylation at the GNAS locus consistent with the diagnosis of PHP type 1b.
Conclusion: PHP-Ib is the result of defects in the methylation pattern of the complex GNAS locus and can be inherited in an autosomal-dominant manner or may occur sporadically. The human GNAS gene is located on chromosome 20q13 and defects are heterogeneous. Genetic counselling is important for the patient and the family, as well as the need for life-long treatment with calcium and activated vitamin D.
01 - 03 Oct 2015
European Society for Paediatric Endocrinology