Background: GH deficiency due to iron overload is well known in thalassaemic children, yet this association has not been described in children with haemochromatosis.
Case report and methods: We report on a girl who was first seen at the age of 9.6 years (height 117.5 cm, −3.3 SDS, weight 21 kg, −2.5 SDS). She had a normal physical examination and was prepubertal. Target height-SDS was −0.9. Her bone age was delayed by 10 months. IGF1 was 78.7 ng/ml (−2.17 SDS), IGFBP3 2.4 mg/l (−1.7 SDS). Thyroid hormones, tissue-transglutminase-IgA as well as liver function tests were normal. Her caryotype was 46,XX. Ferritin concentration was 1136 μg/l (50400), transferrin 2.1 g/l (1.83.3), transferrin-saturation 23% (1550). For genetic analysis of haemochromatosis genomic DNA was isolated.
Results and follow-up: Analysis of the ferroportin-1-gene and the HFE-gene revealed a heterozygote point mutation Arg88Gly in the ferroportin-1-gene and a heterozygote point mutation His63Asp in the HFE-gene. A first GH stimulation test (insulin induced hypoglycaemia) showed a maximal GH of 14.5 ng/ml (expected normal peak>10 ng/ml).
Two years later, at the age of 12 years (height 130.1 cm, −2.6 SDS; weight 26.8 kg, −2.4 SDS) her pubertal development corresponded to a Tanner stage 3 and bone age was delayed by 18 months. IGF1 was 116 ng/ml (−1.86 SDS) and IGFBP3 3.3 mg/l (−2.86 SDS). Because of persistent growth failure a second GH stimulation test (insulin induced hypoglycaemia) was performed which showed a maximal GH of 7.8 ng/ml suggesting partial GH deficiency. A MR of the pituitary gland could not be performed because of the presence of an orthodontic device.
Conclusion: This is the first case of patient with digenic heterozygote mutations in the ferroportin-1 and HFE-genes and isolated partial GH deficiency. We hypothesize that iron overload in the pituitary developed over time and interferes with GH secretion causing growth failure in our patient.
Prague, Czech Republic
24 - 28 Apr 2010
European Society of Endocrinology