Laron sendromlu 5 olgu: Klinik ve moleküler değerlendirme

Laron sendromu, primer büyüme hormon direnci veya duyarsızlığı olarak tanımlanan bir hastalıktır. Bu çalışmada kliniğimizde izlenen Laron sendromu tanılı olguların klinik, laboratuvar ve "Büyüme Hormon Reseptor" gen mutasyonlarının değerlendirilmesi amaçlandı. Beş (2 kız, 3 erkek) olgunun, tedavi öncesi boy SDS, yıllık büyüme hızları, büyüme hormonu, IGF-1, IGF-BP3 düzeyleri, tedavi başlama yaşı, tedavini etkinliğini belirlemek amacıyla tedavinin birinci, ikinci ve üçüncü yıllarında boy SDS ve yıllık büyüme hızı ölçümleri, hedeflenen ve kullanılabilen ilaç dozları (mg/kg/yıl) değerlendirildi. "Büyüme Hormon Reseptor" gen mutasyonları çalışıldı. Tanıda ortalama yaş 3,0±2,7 yıl, boy SDS -5,06±0,7, hedef boy SDS -0,72±0,95, tedavi öncesi yıllık büyüme hızı 3,5±1,7 cm idi. Laboratuvar incelemelerinde bazal büyüme hormonu tüm hastalarda 40 pg/ml üzerinde, bazal IGF-1 düzeyleri 9,7±9,9 ng/ml, IGF jenerasyon testine ortalama IGF yanıtı 10,7±9,8 ng/ml saptandı. İlaç temininde oluşan aksaklıklar nedeni ile rekombinant IGF-1 tedavisine başlama yaşı 4,06±2,6 idi. Yıllık uygulanan ilaç miktarlarının genel olarak hedeflenen düzeyin altında kaldığı saptandı. Olguların ortalama yıllık büyüme hızı tedavinin 1. yılında; 3,73 cm/yıl, 2. yılında 4,24 cm/yıl, 3. yılında 3,55 cm/yıl olarak bulundu. Olguların birinde "Büyüme Hormon Reseptor" geninde homozigot missense c.1630 A>C (p.I544L) mutasyon ve iki kardeşte c.1419 C>T (p.S473S) polimorfizmi, 1 olguda c.1681 C>A (p.P561T) homozigot mutasyonu, 1 olguda c.629 T>G (p.V210G) ve c.1567 A>C (p.I526L) bileşik heterozigot mutasyonu saptandı. Sonuç olarak, Laron sendrom'lu bu olgularda rekombinant IGF-1 tedavisine yeterli klinik yanıt olmadığı gösterildi.

Five cases with Laron syndrome: Clinical and molecular evaluation

Laron Syndrome is defined as primary growth hormone resistance or insensitivity. Our aim is to discuss the clinical,laboratory findings and growth hormone receptor gene mutation analysis of the Laron Syndrome cases.5 patients'(two girls, 3 boys) pretreatment height standard deviation score (SDS), annual growth rates, growth hormone, and IGF-1, IGFBP3 levels , age at initial treatment age, and also the height SDS, and annual growth rates, at first, second, and third years of the treatment, the doses of the targeted drugs which can be used were evaluated to find the effectiveness of the treatment.Growth hormone receptor gene mutations were evaluated. The mean age was 3.0±2.7 years, height SDS was -5.06±0.7 and target height SDS was -0.72±0.95. Pretreatment annual growth rate was 3.5±1.7 cm (1.8-6.0). Baseline growth hormone levels were over 40 pg/ml in all patients. Mean baseline IGF, mean IGF response to IGF generation test values were 9.7±9.9 ng/ml, and 10.7±9.8 ng/ml, respectively. Due to the difficulties to get the recombinant IGF treatmen, we could start the therapy at the mean age of 4.06±2.6 years. Usually the doses of the drugs used per year were under the targeted doses for the patients. The average annual growth rates were 3.73 cm/year, 4,24 cm/year, 3,55 cm/year, at 1st, second and third years, respectivelly. Growth hormone receptor gene analysis revealed homozygote missense c.1630 A>C(p.I544L) mutation in one patient and; c.1419 C>T(p.S473S) polymorphism in two siblings and c.1681 C>A(p.P561T) homozygous mutation in one patient, c.629 T>G(p.V210G) ve c.1567 A>C(p.I526L) compound heterozygous mutation in one patient. As a result, it has been demonstrated that cases with Laron syndrome patients do not give adequate clinical response to recombinant IGF treatment.

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