TY - JOUR
T1 - Total absence of functional acid labile subunit, resulting in severe insulin-like growth factor deficiency and moderate growth failure
AU - Hwa, Vivian
AU - Haeusler, Gabriele
AU - Pratt, Katherine L.
AU - Little, Brian M.
AU - Frisch, Herwig
AU - Koller, Dieter
AU - Rosenfeld, Ron G.
PY - 2006/5
Y1 - 2006/5
N2 - Context: Primary IGF deficiency (IGFD) describes the condition in which serum concentrations of IGF-I are low in the face of normal to elevated GH production. Because IGF-I, which circulates as part of a ternary complex with IGF binding protein (IGFBP)-3 and acid-labile subunit (ALS), mediates the growth-promoting effects of GH, IGFD is associated with severe growth failure in humans. Objective: We investigated a case of IGFD in which serum IGF-I and IGFBP-3 were abnormally low, yet growth failure was modest (-2.1 SD score at 15.5 yr of age). Results: The young male subject, from a consanguineous pedigree, had a postnatal growth profile consistently below the third percentile. The subject had a normal fasting GH level of 3.7 μU/ml and normal serum GH binding protein level (1258 pmol/liter; normal range 431-1892 pmol/liter), but serum IGF-I and IGFBP-3 were profoundly reduced (-5.8 and -7.2 SD score, respectively, at age 12.3 yr), even through puberty. A novel homozygous missense mutation was subsequently identified in the ALS gene, which resulted in severe deficiency of serum ALS (undetectable). Conclusions: ALS is critical for maintaining normal serum concentrations of IGF-I and IGFBP-3, most likely by prolonging the halflives of both proteins. ALS deficiency can be associated with moderate growth failure, but in this patient, the onset and progression of puberty appear to be normal. Altogether the results support a modest role for the ternary complex in the regulation of stature.
AB - Context: Primary IGF deficiency (IGFD) describes the condition in which serum concentrations of IGF-I are low in the face of normal to elevated GH production. Because IGF-I, which circulates as part of a ternary complex with IGF binding protein (IGFBP)-3 and acid-labile subunit (ALS), mediates the growth-promoting effects of GH, IGFD is associated with severe growth failure in humans. Objective: We investigated a case of IGFD in which serum IGF-I and IGFBP-3 were abnormally low, yet growth failure was modest (-2.1 SD score at 15.5 yr of age). Results: The young male subject, from a consanguineous pedigree, had a postnatal growth profile consistently below the third percentile. The subject had a normal fasting GH level of 3.7 μU/ml and normal serum GH binding protein level (1258 pmol/liter; normal range 431-1892 pmol/liter), but serum IGF-I and IGFBP-3 were profoundly reduced (-5.8 and -7.2 SD score, respectively, at age 12.3 yr), even through puberty. A novel homozygous missense mutation was subsequently identified in the ALS gene, which resulted in severe deficiency of serum ALS (undetectable). Conclusions: ALS is critical for maintaining normal serum concentrations of IGF-I and IGFBP-3, most likely by prolonging the halflives of both proteins. ALS deficiency can be associated with moderate growth failure, but in this patient, the onset and progression of puberty appear to be normal. Altogether the results support a modest role for the ternary complex in the regulation of stature.
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U2 - 10.1210/jc.2005-2842
DO - 10.1210/jc.2005-2842
M3 - Article
C2 - 16507628
AN - SCOPUS:33646424087
SN - 0021-972X
VL - 91
SP - 1826
EP - 1831
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 5
ER -