Endocrine Abstracts

Pseudohypoparathyroidism (PHP) is highly heterogeneous rare disorder characterized by end organ resistance to PTH action with proven genetic component. PHP-Ib classically refers to a condition characterized by renal resistance to PTH in the absence of other endocrine or physical abnormalities and in the presence of a normal GNAS alfa activity and only few cases have been reported so far. We report a case of 43 year old gentleman was diagnosed to have seizures at the age of 13 and was commenced on anti-epileptic medication. During the work up for cataract at the age of 31, he was found to have low calcium. As his seizures were thought to be related to hypocalcaemia, his antiepileptic medications were stopped and he was commenced on alfacalcidol and calcium supplements. His older brother and nephews were also later found to have low calcium. His thyroid function and pituitary profile were within the normal range. He had elevated parathyroid hormone levels with normal 25 hydroxy vitamin D and normal adjusted calcium levels. On genetic testing, GNAS sequencing was normal but Methylation of GNAS showed complete loss of the maternal methylation pattern, confirming the diagnosis of pseudohypoparathyroidism type 1b, without the features of short stature, developmental delay and short metacarpals. PHP Ib is most often a sporadic disorder, but sex-linked autosomal dominant inheritance has been reported. In inherited cases, PTH resistance in PHP type 1B develops only after maternal transmission of the molecular defect, whereas paternal transmission of the defect is not associated with PTH resistance. This case emphasises the importance of appropriate referral and timely management as the diagnosis of such rare disorders is often delayed, leading to an initially inappropriate management.