Mini Review

Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences
Horacio M. Domené^a, Vivian Hwa^g, Jesús Argente^b, Jan M. Wit^d, Cecilia Camacho-Hübner^c, Héctor G. Jasper^a, Jesús Pozo^b, Hermine A. van Duyvenvoorde^d-f, Shoshana Yakar^h, Olga V. Fofanova-Gambetti^g, Ron G. Rosenfeld^g, on behalf of The International ALS Collaborative Group

^aCentro de Investigaciones Endocrinológicas (CEDIE-CONICET), Hospital de Niños R. Gutiérrez, Buenos Aires, Argentina;
^bHospital Infantil Universitario Niño Jesús, Departament of Endocrinology, Universidad Autónoma de Madrid, Departament of Pediatrics y CIBER Fisiopatología, Obesidad y Nutrición, Instituto de Salud Carlos III, Madrid, Spain;
^cPediatric Endocrinology, Women and Child Health, Karolinska Institute, Stockholm, Sweden;Departments of
^dPediatrics,
^eEndocrinology and Metabolism, and
^fClinical Genetics, Leiden University Medical Center, Leiden, The Netherlands;
^gDepartment of Pediatrics, Oregon Health and Science University, Portland, Oreg., and
^hEndocrine Divisions, Mount Sinai School of Medicine, New York, N.Y., USA

Address of Corresponding Author

Horm Res 2009;72:129-141 (DOI: 10.1159/000232486)

  Key Words

• Acid-labile subunit
• Insulin-like growth factor-I
• Insulin-like growth factor binding protein
• Growth hormone insensitivity
• Insulin insensitivity
• IGFALS gene mutations

  Abstract

The majority of insulin-like growth factor (IGF)-I and IGF-II circulate in the serum as a complex with the insulin-like growth factor binding protein (IGFBP)-3 or IGFBP-5, and an acid-labile subunit (ALS). The function of ALS is to prolong the half-life of the IGF-I-IGFBP-3/IGFBP-5 binary complexes. Fourteen different mutations of the human IGFALS gene have been identified in 17 patients, suggesting that ALS deficiency may be prevalent in a subset of patients with extraordinarily low serum levels of IGF-I and IGFBP-3 that remain abnormally low upon growth hormone stimulation. Postnatal growth was clearly affected. Commonly, the height standard deviation score before puberty was between -2 and -3, and approximately 1.4 SD shorter than the midparental height SDS. Pubertal delay was found in 50% of the patients. Circulating IGF-II, IGFBP-1, -2 and -3 levels were reduced, with the greatest reduction observed for IGFBP-3. Insulin insensitivity was a common finding, and some patients presented low bone mineral density. Human ALS deficiency represents a unique condition in which the lack of ALS proteins results in the disruption of the entire IGF circulating system. Despite a profound circulating IGF-I deficiency, there is only a mild impact on postnatal growth. The preserved expression of locally produced IGF-I might be responsible for the preservation of linear growth near normal limits.

Copyright © 2009 S. Karger AG, Basel

  Author Contacts

Horacio M. Domené
Centro de Investigaciones Endocrinológicas (CEDIE-CONICET)
División de Endocrinología, Hospital de Niños R. Gutiérrez
Gallo 1330, Buenos Aires 1425 (Argentina)
Tel. +54 11 4963 5931, Fax +54 11 4963 5930, E-Mail hdomene@cedie.org.ar

  Article Information

H.M.D. and H.G.J. are members of the Sociedad Latino-Americana de Endocrinología Pediátrica (SLEP); J.A., J.M.W., C.C.-H., J.P., O.V.F.-G., and R.G.R. are members of the European Society for Paediatric Endocrinology (ESPE).

Received: January 30, 2009
Accepted: June 15, 2009
Published online: September 1, 2009
Number of Print Pages : 13
Number of Figures : 2, Number of Tables : 5, Number of References : 65