Changes in plasma amino acids metabolites, caused by long-term IGF-I deficiency, are reversed by IGF-I treatment - A pilot study.

Abstract

Laron Syndrome (LS), (OMIM# 262500), a rare recessively inherited disease caused by deletions or mutations of the GH receptor, gene characterized by dwarfism with low or undetectable serum IGF-I in the presence of high serum GH. In addition to dwarfism, the IGF-I deficiency leads to metabolic abnormalities including aberrations in protein biosynthesis and homeostasis. The only available treatment for LS patients is (r)IGF-I administration. The present study was aimed to determine the plasma concentrations of specific amino acids and their metabolites in the blood of untreated and IGF-I-treated LS patients. The study involved a total of 10 LS patients (3 untreated and 7 treated), 2 heterozygote mothers and 3aged subjects. Forty healthy boys and girls served as controls. The analysis of amino acids and their metabolites was performed using the LC-MS/MS analysis and Waters Acc-Q Tag ultra-derivatization kit. Serum IGF-I levels were measured by a one-step sandwich chemiluminescence immunoassay. The results revealed that long-term IGF-I deficiency in LS patients led to abnormal changes in the plasma amino acids metabolism, such as low levels of plasma citrulline, sarcosine and taurine that increased upon IGF-I replacement. The plasma amino acid levels of the heterozygous family members resembled those of the untreated LS patients, whereas the pattern in the 2 double heterozygote sisters previously treated with IGF-I resembled that of the presently IGF-I-treated patients. In addition, plasma ɑ-amino adipic acid levels were elevated in both untreated and IGF-I-treated patients. In summary our data revealed that LS patients, a condition associated with congenital IGF-I deficiency, have an abnormal plasma amino acid metabolism that is partially restored by IGF-I treatment.

• Authors: Chen Barazani, Haim Werner, Zvi Laron
• Journal: Growth hormone & IGF research : official journal of the Growth Hormone Research Society and the International IGF Research Society (Growth Horm IGF Res) Vol. 52 Pg. 101312 (06 2020) ISSN: 1532-2238 [Electronic] Scotland
• PMID: 32200226 (Publication Type: Journal Article)
• Copyright: Copyright © 2020 Elsevier Ltd. All rights reserved.

Chemical References

• Amino Acids
• Biomarkers
• IGF1 protein, human
• Insulin-Like Growth Factor I

Topics

• Adolescent
• Adult
• Aged
• Aged, 80 and over
• Amino Acids (metabolism)
• Biomarkers (blood)
• Case-Control Studies
• Child
• Child, Preschool
• Female
• Follow-Up Studies
• Growth Disorders (complications)
• Hearing Loss, Sensorineural (complications)
• Humans
• Infant
• Insulin-Like Growth Factor I (administration & dosage, deficiency)
• Laron Syndrome (etiology, metabolism, pathology, prevention & control)
• Male
• Middle Aged
• Pilot Projects
• Prognosis
• Young Adult