What is Multiple Sulfatase Deficiency (MSD)?

Multiple Sulfatase Deficiency (MSD) is an extremely rare, autosomal recessive genetic disorder that is both a leukodystrophy (affecting the brain’s white matter) and a lysosomal storage disease (caused by the accumulation of cellular waste).

MSD is caused by pathogenic variants in the SUMF1 gene, which provides instructions for making the formylglycine-generating enzyme (FGE). FGE is essential for activating all 17 known sulfatase enzymes in the body. Without functional FGE, sulfatases remain inactive, leading to the build-up of toxic substances (such as sulfatides and glycosaminoglycans) in cells and tissues throughout the body.

Because every sulfatase enzyme is affected, MSD combines the features of multiple single-sulfatase deficiencies. This leads to a progressive loss of function across many systems in the body. MSD is estimated to affect fewer than 1 in 500,000 people worldwide.

What are the Symptoms?

The symptoms of MSD vary widely, but may include:

  • Developmental delay and intellectual disability
  • Progressive loss of motor skills and communication abilities
  • Increased muscle stiffness (spasticity)
  • Blindness and hearing loss
  • Difficulty with oral feeding and swallowing
  • Coarse facial features
  • Skeletal abnormalities (progressive dysplasia)
  • Hydrocephalus (fluid on the brain)
  • Skin changes (dry, scaly skin, sometimes with excess hair)

The age of onset and severity depend on the specific SUMF1 variants a child inherits. Traditionally, MSD was classified into three subtypes:

  • Neonatal form – the most severe, with onset at or shortly after birth
  • Late-infantile form – onset within the first 2 years of life
  • Juvenile form – later onset with somewhat slower progression

More recently, MSD is considered a spectrum disorder, with cases described as attenuated (milder) or severe, rather than falling neatly into subtype categories. Symptoms usually appear between infancy and early childhood.

The average life expectancy for a child with MSD is around 13 years, though this can vary.

How is MSD Inherited?

MSD is inherited in an autosomal recessive pattern. This means that a child must receive one non-working copy of the SUMF1 gene from each parent to develop the disease. Parents who carry one non-working copy are called carriers. Carriers typically do not show symptoms.

How is MSD Diagnosed?

Diagnosis can be made through:

  • Biochemical Testing: Low activity of two or more sulfatase enzymes suggests MSD. Urine tests may also show elevated glycosaminoglycans or sulfatides.
  • Genetic Testing: Confirms the diagnosis by identifying biallelic pathogenic variants in SUMF1.

Genetic testing is recommended even after biochemical testing, as it provides a definitive diagnosis.

Is there a treatment for MSD?

Currently, there is no cure for MSD. Treatment focuses on managing symptoms and improving quality of life through expert, proactive, and multidisciplinary care. Supportive care may include physical therapy, seizure management, feeding support, and interventions for vision, hearing, and breathing challenges.

Research is ongoing, and there is hope for future clinical trials that may lead to disease-modifying therapies.

For more information, visit the Leukodystrophy Care Network page.

Helpful Resources

Leukodystrophy Care Network
Hunter’s Hope Foundation – Family Care
MSD Patient Resource Guide
Clinical Guidelines for MSD
United MSD Foundation