title: Long-term follow-up of a pseudohypoparathyroidism type 1A patient with missense mutation (Pro115Ser) in exon 5.
abstract: Pseudohypoparathyroidism (PHP) refers to end-organ resistance that primarily impairs the renal actions of parathyroid hormone (PTH). The patients with PHP type Ia (PHP-Ia), one of the 4 types of PHP, show resistance to other peptide hormones as well as clinical features of Albright hereditary osteodystrophy (AHO), a constellation of short stature, obesity, brachydactyly, ectopic ossifications, and/or mental retardation. Here we report clinical follow-up for a long-term period in a PHP-Ia case who had a missense mutation leading to the substitution of proline by serine (Prol115Ser) in exon 5 which has been reported previously in only two patients. An 11-year-old boy applied for hand spasm to our hospital. On physical examination, he had short stature, round-shaped face and brachydactly. Laboratory evaluation revealed PTH and TSH resistance. Molecular genetic analysis of the GNAS gene revealed a P115S substitution. The patient was followed up for 13 years. Normocalcaemia was achieved with reduced doses of calcitriol (0.25 μg/day) and calcium supplements (40 mg/kg/day). Daily requirement for levothyroxine supplementation was still high (2.3 μg/kg) to achieve euthyroidism. His pubertal development was Tanner stage V and he has no gonadotropin resistance. To our knowledge, this is the first report concerning long-term follow-up of this rare mutation. We believe that despite the genetic heterogeneity of AHO, phenotype/genotype correlations of this kind of rare mutations may help to understand progress of the disease.
authors.affiliation: Ankara University School of Medicine, Department of Pediatrics, Division of Pediatric Endocrinology, Ankara, Turkey. senaysavas@yahoo.com
authors.forename: Şenay
authors.initials: Ş
authors.lastname: Savaş Erdeve
authors.forename: Merih
authors.initials: M
authors.lastname: Berberoğlu
authors.forename: Zeynep
authors.initials: Z
authors.lastname: Şıklar
authors.forename: Olcay
authors.initials: O
authors.lastname: Evliyaoğlu
authors.forename: Olaf
authors.initials: O
authors.lastname: Hiort
authors.forename: Gönül
authors.initials: G
authors.lastname: Öcal
mesh_terms: D002117:Calcitriol / Q000627:therapeutic use; D002648:Child; D002864:Chromogranins; D005091:Exons / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D019205:GTP-Binding Protein alpha Subunits, Gs / Q000235:genetics*; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D011547:Pseudohypoparathyroidism / Q000145:classification / Q000188:drug therapy / Q000235:genetics*; D013997:Time Factors; D014815:Vitamins / Q000627:therapeutic use
chemical_list: D002864:Chromogranins; D014815:Vitamins; C406732:GNAS protein, human; D019205:GTP-Binding Protein alpha Subunits, Gs; D002117:Calcitriol