Human Acid-Labile Subunit Deficiency: Clinical, Endocrine and Metabolic Consequences

HORACIO M. DOMENÉ; VIVIAN HWA; JESÚS ARGENTE; JAN M. WIT; CECILIA CAMACHO-HÜBNER; HÉCTOR G. JASPER; JESÚS POZO; HERMINE A. VAN DUYVENVOORDE; SHOSHANA YAKAR; OLGA V. FOFANOVA-GAMBETTI; RON G. ROSENFELD; ON BEHALF OF THE INTERNATIONAL ALS COLLABORATIVE GROUP.; THE INTERNATIONAL ALS COLLABORATIVE GROUP ARE PAULA A. SCAGLIA AND SONIA V. BENGOLEA (BUENOS AIRES, ARGENTINA).......

HORMONE RESEARCH

Karger

Lugar: Basilea; Año: 2009 vol. 72 p. 129 - 141

0301-0163

The International ALS Collaborative Group are Paula A. Scaglia and Sonia V. Bengolea (Buenos Aires, Argentina); Aida Lteif and Salman Kirmani (Rochester, Minn., USA); Farid H. Mahmud (London, Canada); Jan Frystyk (Aarhus, Denmark); Ad Hermus, T.B. Twickler and Marlies J.E. Kempers (Nijmegen, The Netherlands); Vicente Barrios and Gabriel Á. Martos-Moreno (Madrid, Spain); Alessia David (London, UK); and Stephen Rose (Birmingham, UK). Horm Res 2009; 72(3):129-141. 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