NORMOCHALCAEMIC PSEUDOHYPOPARATHYROIDISM TYPE-1A AND PSEUDOPSEUDOHYPOPARATHYROIDISM IN A FAMILY WITH ALBRIGHT HEREDITARY OSTEODYSTROPHY - ENDOCRINE AND MOLECULAR BIOLOGICAL STUDIES

A German family with Albright hereditary osteodystrophy (AHO) was examined. One female infant clinically presented with mental retardation, round face, obesity, brachymetacarpia and osteoma cutis. She had normal serum levels of calcium and phosphate, whereas PTH and TSH were evaluated. Injection of synthetic 1-38hPTH resulted in a blunted response of plasma and urine cAMP. Therefore, the diagnosis of normocalcaemic pseudohypoparathyroidism type Ia (PHP-Ia) was suggested. The mother presented also with AHO, but she had normal serum levels of calcium, phosphate and PTH, and a rapid increase in plasma cAMP after injection of 1-38hPTH, suggesting pseudopseudohypoparathyroidism (pseudo-PHP). In Northern blot experiments healthy and AHO-affected family members showed almost the same expression of mRNA coding for the G protein that stimulates the adenylyl cyclase (G(Salpha)). This suggests a mutation of the translation initiator codon of the G(Salpha)-gene, leading to normal steady-state levels of G(Salha)-mRNA, but to an aberrant form of G(Salpha)-protein.