BabyScreen+ newborn screening

Gene: CBS

Green List (high evidence)

Upgraded to Green following reassessment of mapping issues on WGS vs ES.

Created: 21 Oct 2023, 5:52 a.m. | Last Modified: 21 Oct 2023, 5:52 a.m.

Panel Version: 1.107

Well established gene-disease association.

Multi-system disorder, onset in infancy.
In general, individuals appear normal at birth but have a progressive disease course if untreated. Clinical features typically manifest in the first or second decade of life. Intellectual disability may be the first recognizable sign and may present as developmental delay after the first to second year of life. Myopia typically occurs after age one with the majority of untreated individuals developing ectopia lentis by age 8. Roughly half of patients show signs of osteoporosis by their teens. Cerebrovascular events typically manifest during young adulthood, though they have been reported earlier. Thromboembolism is the major cause of early death and morbidity. Among B₆-responsive individuals, a vascular event in adolescence or adulthood is often the presenting feature.

Treatment: vitamin B6 (pyridoxine), methionine-restricted diet, folate, vitamin B12, betaine. Management guidelines PMID 27778219.

Non-genetic confirmatory testing: plasma total homocysteine and plasma amino acids

Paediatric actionable gene by ClinGen.

Note excluded from reproductive carrier screening tests due to poor mappability: downgraded to Amber for now.

Created: 29 Sep 2022, 7:14 a.m. | Last Modified: 19 Oct 2022, 6:46 a.m.

Panel Version: 0.585

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Homocystinuria (MIM# 236200)

Publications

• 27778219

Green List (high evidence)

is on the current VCGS newborn screening panel

Created: 26 Sep 2022, 2:12 a.m. | Last Modified: 26 Sep 2022, 2:12 a.m.

Panel Version: 0.199

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal