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| Genomic newborn screening: ICoNS v0.31 | BCKDHB | Zornitza Stark Marked gene: BCKDHB as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.31 | BCKDHB | Zornitza Stark Gene: bckdhb has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.31 | BCKDHB | Zornitza Stark Phenotypes for gene: BCKDHB were changed from to Maple syrup urine disease, type Ib, MIM# 248600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.30 | BCKDHB | Zornitza Stark Classified gene: BCKDHB as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.30 | BCKDHB | Zornitza Stark Gene: bckdhb has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.29 | BCKDHB | Zornitza Stark reviewed gene: BCKDHB: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Maple syrup urine disease, type Ib, MIM# 248600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.29 | BCKDHB |
José Manuel González de Aledo Castillo gene: BCKDHB was added gene: BCKDHB was added to Genomic newborn screening: ICoNS. Sources: Expert Review,Literature Mode of inheritance for gene: BCKDHB was set to BIALLELIC, autosomal or pseudoautosomal Added comment: Gene disease association evidence: Disease: Maple syrup urine disease type 1A (MSUD1B), autosomal recessive. Gene: BCKDHB encodes the E1β subunit of the branched-chain α-ketoacid dehydrogenase complex. Loss of function at the protein level reduces BCKD activity and causes toxic accumulation of branched-chain amino acids and ketoacids. BCKDHB variants account for ~35% of MSUD cases Curation by ClinGen: ClinGen gene–disease validity: Definitive Treatability and evidence behind that including impact of treatment: Standard care is dietary leucine restriction, BCAA-free supplements, supplementation with isoleucine and valine as needed, and frequent biochemical monitoring. Acute metabolic crises need urgent metabolic management. Early treatment of asymptomatic infants detected by NBS means that most who would have developed neonatal manifestations remain asymptomatic with good treatment adherence . NBS cases has better survival than clinically diagnosed cases: 62.5% versus 5.2% For severe MSUD, liver transplantation can be an option Issues with genomic screening Main problem would be turnaround time Any variants of interest The pathogenic spectrum is dominated by missense variants, also there also reported truncating variants. c.548G>C (p.Arg183Pro): well-known Ashkenazi Jewish founder variant. Who has excluded in genomic newborn screening it and why: BeginNGS in previous genelists, now included Traditional newborn screening in any jurisdiction: Included in RUSP and most NBS wordlwide Sources: Expert Review, Literature |
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