title: Sodium phenylbutyrate decreases plasma branched-chain amino acids in patients with urea cycle disorders.
abstract: Sodium phenylbutyrate (NaPBA) is a commonly used medication for the treatment of patients with urea cycle disorders (UCDs). Previous reports involving small numbers of patients with UCDs have shown that NaPBA treatment can result in lower plasma levels of the branched-chain amino acids (BCAA) but this has not been studied systematically. From a large cohort of patients (n=553) with UCDs enrolled in the Longitudinal Study of Urea Cycle Disorders, a collaborative multicenter study of the Urea Cycle Disorders Consortium, we evaluated whether treatment with NaPBA leads to a decrease in plasma BCAA levels. Our analysis shows that NaPBA use independently affects the plasma BCAA levels even after accounting for multiple confounding covariates. Moreover, NaPBA use increases the risk for BCAA deficiency. This effect of NaPBA seems specific to plasma BCAA levels, as levels of other essential amino acids are not altered by its use. Our study, in an unselected population of UCD subjects, is the largest to analyze the effects of NaPBA on BCAA metabolism and potentially has significant clinical implications. Our results indicate that plasma BCAA levels should to be monitored in patients treated with NaPBA since patients taking the medication are at increased risk for BCAA deficiency. On a broader scale, these findings could open avenues to explore NaPBA as a therapy in maple syrup urine disease and other common complex disorders with dysregulation of BCAA metabolism.
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Lindsay C
authors.initials: LC
authors.lastname: Burrage
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA.
authors.forename: Mahim
authors.initials: M
authors.lastname: Jain
authors.affiliation: University of South Florida, Tampa, FL, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Gandolfo
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA; Howard Hughes Medical Institute, Houston, TX, USA.
authors.forename: Brendan H
authors.initials: BH
authors.lastname: Lee
authors.affiliation: Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX, USA. Electronic address: Nagamani@bcm.edu.
authors.forename: Sandesh C S
authors.initials: SC
authors.lastname: Nagamani
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000597:Amino Acids, Branched-Chain / Q000097:blood* / Q000172:deficiency; D000601:Amino Acids, Essential / Q000097:blood; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D022124:Hyperammonemia / Q000209:etiology; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D010654:Phenylbutyrates / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D056806:Urea Cycle Disorders, Inborn / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy*; D055815:Young Adult
chemical_list: D000597:Amino Acids, Branched-Chain; D000601:Amino Acids, Essential; D010654:Phenylbutyrates
keywords: Branched-chain amino acids; Sodium phenylbutyrate; Urea cycle disorder