2 research outputs found
A cautionary tale of pyridoxine toxicity in cystathionine betaâsynthase deficiency detected by twoâtier newborn screening highlights the need for clear pyridoxine dosing guidelines
Classic homocystinuria is due to deficiency of cystathionine betaâsynthase (CBS), a pyridoxineâdependent enzyme that, depending on the molecular variants, may be coâfactor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a twoâtier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, coâfactor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with highâdose pyridoxine to determine responsiveness. Here we describe our NBSâidentified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weightâbased dosing and duration recommendations for pyridoxine challenge in neonates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163455/2/ajmga61815.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163455/1/ajmga61815_am.pd
A cautionary tale of pyridoxine toxicity in cystathionine betaâsynthase deficiency detected by twoâtier newborn screening highlights the need for clear pyridoxine dosing guidelines
Classic homocystinuria is due to deficiency of cystathionine betaâsynthase (CBS), a pyridoxineâdependent enzyme that, depending on the molecular variants, may be coâfactor responsive. Elevated methionine is often used as the primary analyte to detect CBS deficiency (CBSD) on newborn screening (NBS), but is limited by increased detection of other biochemical disorders with less clear clinical significance such as methionine aminotransferase (MAT) I/III heterozygotes. Our state has implemented a twoâtier NBS algorithm for CBSD that successfully reduced the number of MATI/III heterozygotes, yet effectively detected a mild, coâfactor responsive form of CBSD. After initial diagnosis, newborns with CBSD often undergo a pyridoxine challenge with highâdose pyridoxine to determine responsiveness. Here we describe our NBSâidentified patient with a mild form of pyridoxine responsive CBSD who developed respiratory failure and rhabdomyolysis consistent with pyridoxine toxicity during a pyridoxine challenge. This case highlights the need for weightâbased dosing and duration recommendations for pyridoxine challenge in neonates.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/163455/2/ajmga61815.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/163455/1/ajmga61815_am.pd