Endocrine Abstracts (2010) 22 P510

Growth failure in a girl harbouring digenic heterozygote mutations in the Ferroportin1-gene and the HFE-gene

Marco Janner1, Christa Flück1, Sabina Galllati2 & Primus Mullis1


1Paediatric Endocrinology, Diabetology and Metabolism, University Children’s Hospital, 3010 Bern, Switzerland; 2Human Genetics, University Children’s Hospital, 3010 Bern, Switzerland.


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 (50–400), transferrin 2.1 g/l (1.8–3.3), transferrin-saturation 23% (15–50). 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.

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