Biochemical phenotype and its relationship to treatment in 16 individuals with PCCB c.1606A > G (p.Asn536Asp) variant propionic acidemia.
Treatment; Phenotype; Biomarker; Propionic acidemia
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.
Wenger O;Brown M;Smith B;Chowdhury D;Crosby AH;Baple EL;Yoder M;Laxen W;Tortorelli S;Strauss KA
Molecular Genetics and Metabolism
2020
2020-10-03
journalArticle
<a href="http://doi.org/10.1016/j.ymgme.2020.09.006" target="_blank" rel="noreferrer noopener">10.1016/j.ymgme.2020.09.006</a>
Intravenous infusion of iPSC-derived neural progenitors expressing GCase ameliorates alpha-synuclein aggregates in a mouse model of Gaucher disease
Endocrinology & Metabolism; Genetics & Heredity; medicine; Research & Experimental
Peng Y Y; Liou B; Inskeep V; Blackwood R; Fleming S; Mayhew C N; Sun Y
Molecular Genetics and Metabolism
2019
2019-02
Journal Article
<a href="http://doi.org/10.1016/j.ymgme.2018.12.295" target="_blank" rel="noreferrer noopener">10.1016/j.ymgme.2018.12.295</a>