The role of acid-labile subunit (ALS) in aetiology and diagnostic procedures of short stature
Authors:
L. Toni 1; K. Pádrová 2; L. Plachý 1; P. Dušátková 1; L. Elblová 1; S. Koloušková 1; M. Pechová 2; M. Šnajderová 1; Z. Šumník 1; Š. Průhová 1; J. Lebl 1
Authors place of work:
Pediatrická klinika a 2Ústav lékařské chemie a klinické biochemie 2. lékařské fakulty UK a Fakultní nemocnice Motol, Praha
1
Published in the journal:
Čes-slov Pediat 2020; 75 (4): 214-218.
Category:
Summary
Aims: Acid-labile subunit (ALS) as a glycoprotein component of the ternary complex IGF-1/IGFBP-3/ALS co-regulates bioactivity and prolongs half-life of IGF-1 and thus substantially contributes to regulation of statural growth. Protein component of ALS is encoded by IGFALS gene. We studied the impact of growth hormone (GH) on circulating levels of ALS and additional ternary complex components, and the option to identify carriers of pathogenic variants of IGFALS gene according to low ALS levels.
Methods: We studied interrelations between ternary complex components in 511 children on GH therapy. Children with low ALS levels underwent IGFALS sequencing. We monitored the effect of GH therapy on the ternary complex in 23 children treated for GH deficiency (GHD) or for short stature after having been born small for gestational age (SGA-SS).
Results: In 511 children with GHD and/or SGA-SS on long-term GH therapy ALS level was 8750 µg/l (median; Q1-Q3: 6353–10963), IGF-1 was 233 µg/l (Q1-Q3: 147–329), corresponding to +1.21 SD (Q1-Q3: from -0.11 to +2.45), and IGFBP-3 was 5660 µg/l (Q1-Q3: 4668–6800), corresponding to +3.65 SD (Q1-Q3: from +1.81 to +5.97 SD). ALS is strongly interrelated with IGF-1 (r=0.70; p<0.0001) and with IGFBP-3 (r=0.61; p<0.0001). IGFALS Sanger sequencing in three children with low ALS levels (369, 487 and 1490 µg/l) displayed normal results. In 23 children following 3–4 months of GH therapy, ALS increased from 4859 (median; Q1-Q3: 4176-6240) to 6681 (5413-8332) µg/l (p=0.0004), IGF-1 from 68 (46-114) to 146 (84-178) µg/l (p<0.0001) and IGFBP-3 from 3390 (2820–4030) to 4700 (3940–5300) µg/l (p<0.0001). The impact of GH is more pronounced in IGF-1 (213% increase) compared to IGFBP-3 (132%; p<0.0001) and ALS (139%; p<0.0001).
Conclusions: Our results suggest that estimation of ALS levels is ineffective to detect IGFALS gene mutations. Biochemical measurements of ALS do not substantially contribute to diagnostic work-up and to follow-up in short stature children, according to our experience.
Keywords:
Growth hormone – acid-labile subunit – IGF-1 – IGFBP-3 – ternary complex – IGFALS
Zdroje
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Štítky
Neonatology Paediatrics General practitioner for children and adolescentsČlánok vyšiel v časopise
Czech-Slovak Pediatrics
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