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Gene: SUMF1

Green List (high evidence)

- Multisystem lysosomal storage disorder with variable age of onset and wide variability in clinical presentation and rate of progression. Initial symptoms can present from infancy through early childhood.
- Several different clinical subtypes of MSD have been described based on age of onset, rate of progression and disease severity:
1. Neonatal MSD is the most severe with presentation in the prenatal period or at birth with rapid progression and death occurring within the first two years of life.
2. Infantile MSD is the most common variant and may be characterized as attenuated (slower clinical course with cognitive disability and neurodegeneration identified in the 2nd year of life) or severe (loss of the majority of developmental milestones by age 5 years).
3. Juvenile MSD is the rarest subtype with later onset of symptoms and subacute clinical presentation.

- Genotype-phenotype correlation:
1. Biallelic nonsense variants and deletions are associated with a severe neonatal presentation
2. Biallelic p.(Gly263Val) or p.(Ala279Val) missense variants are associated with attenuated late-infantile MSD
3. Biallelic p.Ser155Pro, p.Gly247Arg, or p.Arg349Trp missense variants are associated with severe late-infantile MSD

- Individuals with unstable SUMF1 protein and low residual FGE activity display a severe late-infantile onset phenotype with rapid progression of MSD and neurologic deterioration
- Individuals with higher levels of residual FGE enzyme activity often have attenuated forms of MSD with fewer symptoms, slower disease progression, and later onset of regression

Created: 8 Jan 2025, 6:11 a.m. | Last Modified: 8 Jan 2025, 6:11 a.m.

Panel Version: 1.992

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Multiple sulfatase deficiency (MIM#272200)

Publications

• 30896912

Variants in this GENE are reported as part of current diagnostic practice