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: Şenay Savaş Erdeve, Merih Berberoğlu, Zeynep Şıklar, Olcay Evliyaoğlu, Olaf Hiort, Gönül Öcal
• Journal: Journal of clinical research in pediatric endocrinology (J Clin Res Pediatr Endocrinol) Vol. 2 Issue 2 Pg. 85-8 ( 2010) ISSN: 1308-5735 [Electronic] Turkey
• PMID: 21274345 (Publication Type: Case Reports, Journal Article)

Chemical References

• Chromogranins
• Vitamins
• GNAS protein, human
• GTP-Binding Protein alpha Subunits, Gs
• Calcitriol

Topics

• Calcitriol (therapeutic use)
• Child
• Chromogranins
• Exons (genetics)
• Female
• Follow-Up Studies
• GTP-Binding Protein alpha Subunits, Gs (genetics)
• Humans
• Male
• Mutation, Missense
• Pedigree
• Pseudohypoparathyroidism (classification, drug therapy, genetics)
• Time Factors
• Vitamins (therapeutic use)