Pseudohypoparathyroidism Type Ia-Clinical Case with a Novel Mutation of GNAS1 Gene

Pseudohypoparathyroidism (PHP) is a rare autosomal dominant disorder resulting from loss of function mutations in the GNAS gene. Several forms of PHP are noted. PHP type 1a occurs most commonly and is characterized by physical features termed Albright’s Hereditary Osteodystrophy (AHO), a constellation of physical features which may include short stature, obesity, round facies, heterotopic ossification, brachydactyly and mental retardation, and increased levels of parathyroid hormone (PTH) due to the end organ hormone resistance to its action. Here we report a new GNAS mutation in a 3.5 years old African American female patient with a history of round facies, developmental delays, obesity and seizure disorder; she was admitted for apneic episode and noted to have prolonged QTc interval on cardiac monitor. A lab evaluation showed severe hypocalcaemia, hyperphosphatemia, high PTH with normal magnesium and alkaline phosphatase levels. She also had slightly elevated Thyroid Stimulating Hormone (TSH) levels indicative of type 1 a PHP where resistance to multiple Gs protein-coupled hormones (e.g. PTH, TSH, Luteinizing Hormone (LH), Follicular Stimulating Hormone (FSH), and Growth Hormone Releasing Hormone (GHRH)) is present. Full genomic DNA sequencing of the exons and adjacent intronic regions of the GNAS gene revealed a novel heterozygous mutation in intron 7, c.585+1G>A, in both the patient and her mother.