Genomic Newborn Screening Expands to 777 Genetic Conditions, a 633% Increase Over Existing U.S. Recommendations
The BRIDGES-NBS study has chosen 777 condition entries, linked to 743 genes, for a project testing whether genome sequencing can be added to newborn screening run by public health laboratories in several U.S. states and territories. In a paper in Genetics in Medicine, the team describes building the list from published resources, then having it revised by clinical experts, molecular geneticists, genetic counsellors, the public health laboratory programs, rare disease advocacy organisations, the study's Community Advisory Board and project leaders at the National Institutes of Health.
Researchers have identified 777 genetic conditions for expanded newborn screening in the United States and United Kingdom, including 671 conditions beyond those classified as core conditions on the U.S. Recommended Uniform Screening Panel (RUSP). The BRIDGES-NBS project describes the largest collection of genetic conditions and genes proposed for genomic newborn screening, representing a 633% increase in the number of conditions evaluated compared with the 106 entries classified as core RUSP conditions.
Inherited immune disorders, known as inborn errors of immunity, account for 37.2% of the entries, followed by inherited metabolic disorders (18.7%) and endocrine disorders (18.1%). Importantly, 93.3% of the entries have an available non-genetic confirmatory test, providing a pathway to verify screening results before clinical intervention.
For each condition, the researchers documented the benefits of early detection, characteristic symptoms, laboratory findings, and available treatments or monitoring strategies. The collection also includes one copy number variant, involving a deletion or duplication of DNA, and two chromosomal aneuploidies, in which an individual has an extra or missing chromosome.
Where early detection can save lives
The clinical benefits of expanded newborn screening are particularly significant for conditions where treatment before symptoms appear can prevent irreversible damage or life-threatening complications. Five examples illustrate the potential impact:
- Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency (ACADM, core RUSP): This inherited metabolic disorder prevents the body from properly breaking down certain fats for energy. Without treatment, it can cause dangerously low blood sugar and potentially fatal complications. Early detection allows medical evaluation within one to two days and preventive measures, including feeding the newborn every three to four hours until a specialist provides further guidance.
- Galactosemia (GALT, core RUSP): Babies with this condition cannot properly metabolise galactose, a sugar found in milk. Within days of consuming lactose-containing milk, affected newborns can develop dangerously low blood sugar, liver damage and life-threatening E. coli infections. Early diagnosis allows an immediate switch to a suitable lactose-free formula, helping prevent these complications.
- Spinal muscular atrophy (SMN1, core RUSP): This genetic disorder progressively damages the nerve cells responsible for controlling muscles, leading to muscle weakness and wasting. Identifying affected newborns before symptoms appear allows treatment to begin when it is most effective, potentially preserving muscle function and preventing severe disability.
- Long QT syndrome (KCNH2, not a core RUSP condition): This inherited heart condition disrupts the electrical signals controlling the heartbeat and can cause dangerous, potentially fatal heart rhythms. Early detection lets doctors start preventive treatments, including beta blockers, which reduce the risk of life-threatening cardiac events.
- Ornithine transcarbamylase deficiency (OTC, not a core RUSP condition): This inherited metabolic disorder prevents the body from properly removing ammonia, a toxic waste product. Dangerous ammonia accumulation can cause irreversible brain injury or death, sometimes shortly after birth. Early diagnosis enables dietary management, medication and emergency treatment to prevent or reduce these complications.
The 106 entries already represented in U.S. newborn screening recommendations
The following gene symbols and chromosomal abnormalities are classified as core RUSP entries in the BRIDGES-NBS spreadsheet, grouped into eight clinical categories.
Some genes, including FOXN1, PTPN11 and RAC2, appear in multiple entries because they are associated with distinct conditions. The RUSP also includes critical congenital heart disease and hearing loss, which are screened using non-genetic methods such as pulse oximetry and hearing tests.
Inherited metabolic disorders (34 entries): ACADM, ACADVL, ACAT1, ARSA, ASL, ASS1, BCKDHA, BCKDHB, BTD, CBS, DBT, FAH, GAA, GALC, GALT, GAMT, GCDH, HADHA, HADHB, HLCS, HMGCL, IDS, IDUA, IVD, MCCC1, MCCC2, MMAA, MMAB, MMUT, MTHFR, PAH, PCCA, PCCB, SLC22A5
Inborn errors of immunity (21 entries): ADA, AK2, CD3D, CD3E, CORO1A, DCLRE1C, FOXN1, IL2RG, IL7R, JAK3, LAT, LCP2, LIG4, NHEJ1, PRKDC, PTPRC, RAC2, RAG1, RAG2
Cardiac disorders (19 entries): 22q11.2 region, BRAF, KDM6A, KMT2D, KRAS, LZTR1, MAP2K1, Monosomy X, MRAS, NRAS, PRKAR1A, PTPN11, RAF1, RIT1, RRAS2, SOS1, SOS2, Trisomy 21
Endocrine disorders (14 entries): DUOXA2, FOXE1, IGSF1, IRS4, IYD, NKX2-1, PAX8, SLC5A5, TBL1X, TG, THRA, TPO, TRHR, TSHB
Hearing loss disorders (13 entries): ADGRV1, CDH23, CIB2, CLRN1, GJB2, MYO7A, OTOF, PCDH15, SLC26A4, USH1C, USH1G, USH2A, WHRN
Neurologic disorders (3 entries): ABCD1, DMD, SMN1
Pulmonary disorders (1 entry): CFTR
Hematologic disorders (1 entry): HBB
The complete BRIDGES-NBS dataset, including descriptions of each condition, the clinical rationale for screening, reporting criteria and conditions considered but excluded from the current panel, is freely available from the BRIDGES-NBS project website.
By establishing a shared list of genetic conditions, the BRIDGES-NBS study provides participating public health laboratories with a consistent framework for evaluating whether genome sequencing can be integrated into routine newborn screening. The findings could help determine whether population-wide genomic screening is practical, reliable and clinically beneficial, potentially enabling earlier diagnosis and treatment of hundreds of inherited diseases.
Written by the Genomes desk from the primary sources cited and linked above and checked against them. Research use only; not medical advice. Corrections: [email protected].