BabyScreen+ newborn screening

Gene: ARSA

Green List (high evidence)

reatment for metachromatic leukodystrophy

PMID: 25987178
It takes 12 – 24 months after BMT for the disease to stabilise, so if the patient already has clinical disease it will progress during this time.
“Even in asymptomatic patients with the infantile onset type, neurological deterioration and progression of white matter abnormalities on MRI were reported”.


Study by Martin et al 2013 (PMID: 23348427): asymptomatic children with the infantile form stabilise

PMID: 33195324
IV and probably intrathecal ERT doesn’t work

Autologous bone marrow transduced with lentiviral ARSA was effective in a child. The company concerned is registering the therapy with the EMA

So, on balance it looks like treatment (be it BMT or gene therapy delivered to autologous bone marrow) would be of benefit to an asymptomatic child. Therefore, I would suggest we include it the gene.

Created: 19 Oct 2022, 10:59 p.m. | Last Modified: 19 Oct 2022, 10:59 p.m.

Panel Version: 0.588

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• PMID: 25987178
• PMID: 23348427
• PMID: 33195324

Green List (high evidence)

Well established gene-disease association.

Progressive disorder, variable age of onset, including severe infantile forms, which are fatal. However, adult onset also reported.

Treatment: bone marrow transplant.

Clinical trials with intrathecal ARSA, SHP611, among others.

Created: 22 Sep 2022, 1:39 a.m. | Last Modified: 22 Sep 2022, 1:39 a.m.

Panel Version: 0.125

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Metachromatic leukodystrophy, MIM# 250100