ESPE Abstracts

Background: Isolated growth hormone deficiency type IA (IGHD IA) is described in families with homozygous GH1 deletions that arise from unequal recombination and crossing over within the GH gene cluster during meiosis. Patients with IGHD IA show early and severe growth failure and tend to develop antibodies upon treatment with recombinant human growth hormone (rhGH).

Aims: To present the follow−up of three patients with IGHD IA treated with rhGH.

Methods: GH1 gene was analysed by PCR.

Results: Three female patients were included in the study. All patients were of Avars origin and were born from consanguineous marriages. Two girls were second cousins. Me of birth weight was +0.2 SD, Me of birth length +0.5 SD. The patients had typical features of congenital GHD: frontal bossing, doll face, acromicria and truncal obesity. Low height velocity was detected at the age of 3−6 months. The first evaluation showed severe growth retardation: −6.4 SD (1.9 year, case 1), −4.9 SD (1 year, case 2), −7.3 SD (1.6 year, case 3) with normal BMI. IGF-I level was undetectable (less than 3 ng/ml); TSH, fT4, prolactin and cortisol levels were normal. DNA analysis revealed homozygous deletion of GH1 gene in all three patients. Diagnosis of IGHD IA was established. rhGH therapy ("Rastan", Russia) was started at dose 0.033 mg/kg per day. Height and HV were measured at baseline and every 6 months during the treatment period (from 1 to 5 years). IGF-I levels were monitored during therapy and were in the normal limits according to age and sex. HV increased after 2-4 months of rhGH, during the first year of therapy median of growth velocity was 20 cm/year. Over 2 years of treatment (cases 1 and 3), patients' height increased from 60.8 ± 2.5 to 93.9 ± 3.7 cm, with an increase in height SDS from −6.85 ± 0.45 to −0.18 ± 0.05. After 5years' follow-up of patient 3, Δ height SD was +7 and growth velocity was 10.2 cm/year.

Conclusions: GH resistance is not a uniform feature of IGHD IA. The sustained GH response observed in the above cases may be related to the patients' genotypes and/or type of rhGH preparation.