Primary acid-labile subunit deficiency due to recessive IGFALS mutations results in postnatal growth deficit associated with low circulating insulin growth factor (IGF)-I, IGF binding protein-3 levels, and hyperinsulinemia.
J Clin Endocrinol Metab
; 93(5): 1616-24, 2008 May.
Article
en En
| MEDLINE
| ID: mdl-18303074
ABSTRACT
CONTEXT Up to 90% of circulating IGF-I and IGF-II are carried bound to either IGF binding protein (IGFBP)-3 or IGFBP-5 and the acid-labile subunit (ALS) in the form of tertiary complexes that extend their circulating half-life. Three cases of complete ALS deficiency have been recently reported in short-stature patients with very low circulating IGF-I and IGFBP-3 levels who presented with homozygous or compound heterozygous mutations in the ALS encoding gene (IGFALS; 16p13.3), thus supporting a role for ALS in the regulation of the bioavailability of IGFs during postnatal growth. OBJECTIVE:
We present the molecular and clinical characterization of two novel IGFALS mutations that caused complete ALS deficiency in three unrelated patients with postnatal growth deficit, low IGF-I and IGFBP-3 levels, and no GH deficiency.RESULTS:
IGFALS mutation screening identified a novel homozygous IGFALS missense mutation, which altered a conserved residue, N276S, in two of the probands. The third proband presented a novel homozygous nonsense mutation, Q320X, that is predicted to generate a severely truncated ALS protein. The affected probands presented a similar phenotype characterized by a moderate postnatal growth deficit associated with undetectable ALS, low IGF-I, IGF-II, and IGFBP-3, and hyperinsulinemia, and, in two cases, delayed puberty.CONCLUSIONS:
Primary ALS deficiency due to IGFALS mutations should be considered as a possible cause of postnatal growth deficit in IGF-I-deficient patients in the absence of GH deficiency or insensitivity. Determination of serum ALS levels and basal insulinemia can be helpful in the differential diagnosis of patients with idiopathic IGF-I deficiency.
Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Factor I del Crecimiento Similar a la Insulina
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Glicoproteínas
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Proteínas Portadoras
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Proteína 3 de Unión a Factor de Crecimiento Similar a la Insulina
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Trastornos del Crecimiento
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Hiperinsulinismo
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Mutación
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Límite:
Adolescent
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Child, preschool
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Humans
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Male
Idioma:
En
Revista:
J Clin Endocrinol Metab
Año:
2008
Tipo del documento:
Article
País de afiliación:
España