ESPE Abstracts (2015) 84 P-2-426

The Acid-Labile Subunit Dose Matters? Response to Human GH Treatment in Patients with Acid-Labile Subunit Deficiency

Susanne Bechtold, Julia Roeb, Claudia Weissenbacher, Carmen Sydlik & Heinrich Schmidt

University Children’s Hospital, Munich, Germany

Background: In patients with acid-labile subunit (ALS) deficiency, the inability to build ternary complexes results in a marked reduction of circulating total IGF1. Height reduction by heterozygosity is about 1 SD in comparison to wild type. In homozygosity or compound heterozygosity a height loss of −2 to −2.5 SD occurs. This is suggestive of a gene-dose effect. How does treatment with human GH influence height development in relation to the underlying genetic defect and the ALS concentration?

Patients: We report on two growth retarded boys with documented ALS deficiency. Patient 1 has a homozygous mutation and undetectable ALS and IGF1 concentrations, and patient 2 has a heterozygous mutation and low levels of ALS and IGF1. Patient 1 had an age of 6.7 years and a height of −3.03 SD and patient 2 an age of 15.8 years and a height of – 1.9 SD when GH treatment was started. After GHD exclusion the patients were treated with GH in escalating doses up to 0.05 mg/kg bw/day.

Results: Patient 1 did not profit from treatment with GH and showed no increase in height-SD. We also used recombinant IGF1 to improve his height development, without any success. There was no change in IGF1 levels throughout treatment. His near final height is −3.0 SD. Patient 2 with low, but detectable IGF1 and ALS levels improved his height during GH treatment and his final height is at −0.4 SD. During GH treatment his IGF1 levels increased.

Discussion: In patients with an absolute deficiency of ALS, treatment with either GH or IGF1 might be without use. However, those patients with low but detectable IGF1 and ALS levels, and a heterozygous mutation, might profit from GH treatment. We speculate that the ALS dose could matter when weighing treatment options in height reduction in ALS deficiency.

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