435 - Metabolomic-Based Amino Acid and Biogenic Amine Plasmatic Profile of Brazilian Cri-du-Chat Patients

Abstract

Cri-du-chat syndrome (CDCS) is a rare innate disease attributed to chromosome 5p deletion characterized by a cat-like cry, craniofacial malformation, and altered behavior of affected children. Here, UHPLC/MS and chemometrics were employed to analyze blood samples withdrawn from CDCS carriers (n=18) and normal parental subjects (n=18), all aged 0-34 years, aiming to set up a representative CDCS profile constructed from 33 targeted amino acids and biogenic amines. Methionine sulfoxide (MetO), nitrotyrosine and His were of particular concern with respect to CDCS redox balance. Increased serotonin (3-fold), methionine sulfoxide (2-fold), and Asp (50%) levels, and a little lower Orn (26%), citrulline (23%), Leu (29%), Val (20%), Ile (16%), Asn (17%), Gln (10%), Trp (15%), Thr (13%), His (12%), Phe (11%), Met (6%), and creatinine (35%) levels were found in the plasma of CDCS patients. Nitrotyrosine did not differ in normal and CDCS individuals, whereas the ratio Trp/Σtotal metabolites was 37% higher in the latter group. The accumulated metabolites may reflect disturbances in the redox balance, deficient purine biosynthesis, and altered behavior, whereas the amino acid abatement in the latter group may affect the homeostasis of the urea cycle, citric acid cycle, branched chain amino acid synthesis, Tyr and Trp metabolism and amino acid biosynthesis. The identification of enzymatic deficiencies leading to the amino acid burden in CDCS is further required for elucidating its molecular bases and eventually propose specific or mixed amino acid supplementation to newborn patients aiming to balance their metabolism. Support: FAPESP, CNPq, CAPES.