Biochemical phenotype and its relationship to treatment in 16 individuals with PCCB c.1606A > G (p.Asn536Asp) variant propionic acidemia.
Title
Biochemical phenotype and its relationship to treatment in 16 individuals with PCCB c.1606A > G (p.Asn536Asp) variant propionic acidemia.
Creator
Wenger O;Brown M;Smith B;Chowdhury D;Crosby AH;Baple EL;Yoder M;Laxen W;Tortorelli S;Strauss KA
Publisher
Molecular Genetics and Metabolism
Date
2020
2020-10-03
Description
Propionic acidemia (PA) is caused by inherited deficiency of mitochondrial propionyl-CoA carboxylase (PCC) and results in significant neurodevelopmental and cardiac morbidity. However, relationships among therapeutic intervention, biochemical markers, and disease progression are poorly understood. Sixteen individuals homozygous for PCCB c.1606A > G (p.Asn536Asp) variant PA participated in a two-week suspension of therapy. Standard metabolic markers (plasma amino acids, blood spot methylcitrate, plasma/urine acylcarnitines, urine organic acids) were obtained before and after stopping treatment. These same markers were obtained in sixteen unaffected siblings. Echocardiography and electrocardiography were obtained from all subjects. We characterized the baseline biochemical phenotype of untreated PCCB c.1606A > G homozygotes and impact of treatment on PCC deficiency biomarkers. Therapeutic regimens varied widely. Suspension of therapy did not significantly alter branched chain amino acid levels, their alpha-ketoacid derivatives, or urine ketones. Carnitine supplementation significantly increased urine propionylcarnitine and its ratio to total carnitine. Methylcitrate blood spot and urine levels did not correlate with other biochemical measures or cardiac outcomes. Treatment of PCCB c.1606A > G homozygotes with protein restriction, prescription formula, and/or various dietary supplements has a limited effect on core biomarkers of PCC deficiency. These patients require further longitudinal study with standardized approaches to better understand the relationship between biomarkers and disease burden.
Subject
Treatment; Phenotype; Biomarker; Propionic acidemia
Identifier
Format
journalArticle
URL Address
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Rights
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ISSN
1096-7206 1096-7192
NEOMED College
NEOMED College of Medicine
NEOMED Department
Department of Pediatrics
Department of General Surgery
NEOMED Student Publications
Update Year & Number
October 2020 List
Affiliated Hospital
Akron Children's Hospital
Summa Health System Akron City Hospital
Citation
Wenger O;Brown M;Smith B;Chowdhury D;Crosby AH;Baple EL;Yoder M;Laxen W;Tortorelli S;Strauss KA, “Biochemical phenotype and its relationship to treatment in 16 individuals with PCCB c.1606A > G (p.Asn536Asp) variant propionic acidemia.,” NEOMED Bibliography Database, accessed December 3, 2022, https://neomed.omeka.net/items/show/11347.