| Date | Panel | Item | Activity | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Genomic newborn screening: ICoNS v0.33 | BCKDHA | Zornitza Stark Marked gene: BCKDHA as ready | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.33 | BCKDHA | Zornitza Stark Gene: bckdha has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.33 | BCKDHA | Zornitza Stark Phenotypes for gene: BCKDHA were changed from to Maple syrup urine disease, type Ia, MIM# 248600 | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.32 | BCKDHA | Zornitza Stark Classified gene: BCKDHA as Green List (high evidence) | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.32 | BCKDHA | Zornitza Stark Gene: bckdha has been classified as Green List (High Evidence). | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.31 | BCKDHA | Zornitza Stark reviewed gene: BCKDHA: Rating: GREEN; Mode of pathogenicity: None; Publications: ; Phenotypes: Maple syrup urine disease, type Ia, MIM# 248600; Mode of inheritance: BIALLELIC, autosomal or pseudoautosomal | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
| Genomic newborn screening: ICoNS v0.29 | BCKDHA |
José Manuel González de Aledo Castillo gene: BCKDHA was added gene: BCKDHA was added to Genomic newborn screening: ICoNS. Sources: Literature Mode of inheritance for gene: BCKDHA was set to BIALLELIC, autosomal or pseudoautosomal Added comment: Gene–disease association evidence: Disease: Maple syrup urine disease type 1A (MSUD1A), autosomal recessive. Gene: BCKDHA encodes the E1α 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. BCKDHA variants account for ~45% 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.1312T>A, p.Tyr438Asn (Old Order/Swiss Mennonites). High prevalence in these populations 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: Literature |
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||