Pseudopseudohypoparathyroidism

A 37-year-old man with a history of bicuspid aortic valve surgically replaced at age 31 years was admitted to our hospital in March, 2013, with 6 weeks of fever and 4 weeks of mild left mandibular pain. On examination we noted that he had short stature (155 cm) and shortened fourth and fifth fingers without fourth or fifth metacarpophalangeal knuckles bilaterally (figure). Hand radiographs confirmed symmetric abnormalities of both hands with shortening of the first and third distal phalanges and fourth and fifth metacarpals bilaterally (figure) consistent with Albright's hereditary osteodystrophy. He had no ectopic calcifications on chest radiograph, serum calcium and phosphate were normal, and he had intact parathyroid hormone (PTH) levels, confirming the diagnosis of pseudopseudohypoparathyroidism. Fuller Albright reported patients with pseudohypoparathyroidism who had short stature, obesity, round facies, shortened metacarpals and metatarsals, and PTH resistance causing hypocalcaemia and hyperphosphataemia in 1942. In 1952 he described patients with the same physical appearance but without PTH resistance, a condition that he termed pseudopseudohypoparathyroidism. Both conditions are caused by loss of function mutations in the α subunit of the Gs protein encoded by the first 13 exons or intervening introns of the complex GNAS gene locus (location 20q13.32). Maternal transmission causes pseudohypoparathyroidism type 1a whereas paternal transmission leads to pseudopseudohypoparathyroidism, a phenomenon known as genomic imprinting. This difference is thought to be caused by the variable expression of GNAS isoforms in tissues arising from the parental origin of the gene. Renal tubular cells predominantly express the maternal allele of GNAS so a paternally inherited mutation results in a normal renal response to PTH. Offspring of a woman with pseudopseudohypoparathyroidism have a 50% chance of pseudohypoparathyroidism type 1a. Pseudopseudohypoparathyroidism needs no treatment, but genetic counselling is recommended. Our patient declined genetic testing. He reported that his father was short in stature but had no hand abnormalities. He was diagnosed with a dental abscess as the underlying cause of his febrile illness and discharged home with oral antibiotics. Contributors All authors cared for the patient and wrote the report. Written consent to publication was obtained.