Complete ALS Deficiency Associated with a Novel Leu409Phe IGFALS Gene Mutation

DOMENÉ, HORACIO; BERGADÁ, IGNACIO; SCAGLIA, PAULA; KARABATAS, LILIANA; BRASLAVSKY, DÉBORA; COHEN, SARA; JASPER, HÉCTOR

Montevideo

Congreso; XXIII Annual Meeting of the Paediatrics Endocrinology Latinoamerican Society; 2012

XXIII Annual Meeting of the Paediatrics Endocrinology Latinoamerican Society

GH insensitivity has been associated to GHR,GHR, STAT5B, IGF1 and IGFALS gene defects. Despite similar degrees of IGF-I deficiency only IGFALS gene defects result in mild growth deficit. Objective: To characterize the molecular defect in a short boy presenting IGF-I and IGFBP-3 deficiencies. Methods: The proband, a 13.8 year old prepubertal boy, born SGA at term (weight 2810 g, –1.2 SDS; height 44 cm, –3.66 SDS) from consanguineous parents (father 160 cm, –1.88 SDS; mother 157 cm, –0.60 SDS), is the fourth of nine siblings, height –2.65 SDS, BA 12.75 years for CA 13.42. Stimulated GH and IGFBP-3 levels were determined by ICMA, IGF-I by RIA, ALS by Western imm unoblot and in vitro ternary complex (TC) formation by size exclusion chromatography., IGF1 and IGFALS gene defects. Despite similar degrees of IGF-I deficiency only IGFALS gene defects result in mild growth deficit. Objective: To characterize the molecular defect in a short boy presenting IGF-I and IGFBP-3 deficiencies. Methods: The proband, a 13.8 year old prepubertal boy, born SGA at term (weight 2810 g, –1.2 SDS; height 44 cm, –3.66 SDS) from consanguineous parents (father 160 cm, –1.88 SDS; mother 157 cm, –0.60 SDS), is the fourth of nine siblings, height –2.65 SDS, BA 12.75 years for CA 13.42. Stimulated GH and IGFBP-3 levels were determined by ICMA, IGF-I by RIA, ALS by Western imm unoblot and in vitro ternary complex (TC) formation by size exclusion chromatography.IGFALS gene defects result in mild growth deficit. Objective: To characterize the molecular defect in a short boy presenting IGF-I and IGFBP-3 deficiencies. Methods: The proband, a 13.8 year old prepubertal boy, born SGA at term (weight 2810 g, –1.2 SDS; height 44 cm, –3.66 SDS) from consanguineous parents (father 160 cm, –1.88 SDS; mother 157 cm, –0.60 SDS), is the fourth of nine siblings, height –2.65 SDS, BA 12.75 years for CA 13.42. Stimulated GH and IGFBP-3 levels were determined by ICMA, IGF-I by RIA, ALS by Western imm unoblot and in vitro ternary complex (TC) formation by size exclusion chromatography.Objective: To characterize the molecular defect in a short boy presenting IGF-I and IGFBP-3 deficiencies. Methods: The proband, a 13.8 year old prepubertal boy, born SGA at term (weight 2810 g, –1.2 SDS; height 44 cm, –3.66 SDS) from consanguineous parents (father 160 cm, –1.88 SDS; mother 157 cm, –0.60 SDS), is the fourth of nine siblings, height –2.65 SDS, BA 12.75 years for CA 13.42. Stimulated GH and IGFBP-3 levels were determined by ICMA, IGF-I by RIA, ALS by Western imm unoblot and in vitro ternary complex (TC) formation by size exclusion chromatography.Methods: The proband, a 13.8 year old prepubertal boy, born SGA at term (weight 2810 g, –1.2 SDS; height 44 cm, –3.66 SDS) from consanguineous parents (father 160 cm, –1.88 SDS; mother 157 cm, –0.60 SDS), is the fourth of nine siblings, height –2.65 SDS, BA 12.75 years for CA 13.42. Stimulated GH and IGFBP-3 levels were determined by ICMA, IGF-I by RIA, ALS by Western imm unoblot and in vitro ternary complex (TC) formation by size exclusion chromatography. Results: He was GH sufficient (22.0 ng/ml), had low IGF-I (–4.15 and –4.70 SDS) and undetectable IGFBP-3 and ALS levels. He was unable to form TC, even after spiking with rhIGFBP-3.He was GH sufficient (22.0 ng/ml), had low IGF-I (–4.15 and –4.70 SDS) and undetectable IGFBP-3 and ALS levels. He was unable to form TC, even after spiking with rhIGFBP-3. IGFALS gene sequencing revealed a homozygous novel missense mutation (c.1225C>T; p.Leu409Phe), predicted to be probably damaging by in silico analysis. Conclusions: Mild growth retardation with pubertal delay associated to severe IGF-I and IGFBP-3 reductions led to the molecular characterization of another ALS deficient patient.gene sequencing revealed a homozygous novel missense mutation (c.1225C>T; p.Leu409Phe), predicted to be probably damaging by in silico analysis. Conclusions: Mild growth retardation with pubertal delay associated to severe IGF-I and IGFBP-3 reductions led to the molecular characterization of another ALS deficient patient.in silico analysis. Conclusions: Mild growth retardation with pubertal delay associated to severe IGF-I and IGFBP-3 reductions led to the molecular characterization of another ALS deficient patient.