Long-term follow-up of a pseudohypoparathyroidism type 1a patient with missense mutation (pro115ser) in exon 5


Erdeve Ş. S. , Berberoǧlu M., Şiklar Z., EVLİYAOĞLU S. O. , Hiort O., Öcal G.

JCRPE Journal of Clinical Research in Pediatric Endocrinology, cilt.2, sa.2, ss.85-88, 2010 (SCI Expanded İndekslerine Giren Dergi) identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 2 Konu: 2
  • Basım Tarihi: 2010
  • Doi Numarası: 10.4274/jcrpe.v2i2.85
  • Dergi Adı: JCRPE Journal of Clinical Research in Pediatric Endocrinology
  • Sayfa Sayıları: ss.85-88

Özet

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. © Journal of Clinical Research in Pediatric Endocrinology.