What is multiple sulfatase deficiency (MSD)?

Multiple sulfatase deficiency (MSD) is a very rare genetic disorder that affects the brain and many other parts of the body. It is a type of leukodystrophy, a group of conditions that affect the white matter of the brain. These conditions damage the myelin sheath — the protective coating around nerve cells in the brain and spinal cord. Myelin helps messages travel quickly between cells in the brain and body. 

Causes of multiple sulfatase deficiency

People with MSD are born with a change in the SUMF1 gene. This gene makes a helpful protein that controls enzymes called sulfatases. Sulfatases break down certain molecules that have sulfate in them. In people with MSD, the protein doesn’t work the way it should, and the sulfate-containing molecules don’t get broken down. Instead, they build up in the body.

In MSD, this buildup harms cells in the brain and other parts of the body. Because of the damage, messages from the brain and spinal cord move more slowly, or don’t get through at all. This causes the symptoms below.

Signs and Symptoms of multiple sulfatase deficiency

There are multiple forms of MSD, based on when symptoms appear: late infantile, early juvenile, late juvenile and adult. Symptoms usually include:

• Seizures
• Delayed development (learning or growing slower than usual)
• Trouble walking
• Trouble speaking
• Eye problems
• Nerve damage
• Breathing problems
• Heart problems
• Skin problems
• Bone and joint changes
• Muscles that are too loose or too tight
• Trouble eating or swallowing
• Constipation 

Testing and diagnosis

In addition to looking at physical symptoms, diagnosing MSD involves several tests: 

• A brain MRI (magnetic resonance imaging) can show patterns in brain tissue that are typical of MSD.
• X-rays can show bone problems in the spine, hands, feet and skull.
• Blood and urine tests, called biochemical testing, check levels of sulfatases and the concentration of compounds that contain sulfate.
• Genetic testing looks for changes in the genes linked to MSD. This test is done from a blood or saliva sample or a cheek swab.

Together, results from these tests give a clear picture and help confirm the diagnosis.

Treatment for multiple sulfatase deficiency

There is currently no cure for MSD, but there are treatments to help manage symptoms and keep children comfortable. Each child’s treatment is unique depending on their symptoms.

Children with MSD should be monitored for:

• Heart and blood vessel changes (checked with EKG and echocardiogram)
• Skin changes
• Bone health issues (may need checkups with an orthopedist or endocrinologist)
• Gallbladder, liver or spleen changes (watched with regular belly scans)
• Eye movement or vision problems (may need testing by an eye doctor)
• Growth or weight changes (possibly linked to feeding problems)
• Breathing changes, including snoring

If any of these conditions are found, pediatric subspecialists can help treat them. Many children with MSD also benefit from physical, occupational and speech therapy to combat challenges caused by the disease.

Follow-up

Children with MSD need regular monitoring by neurologists, as well as ongoing therapy and coordinated care by other medical subspecialists as needed. At Children’s Hospital of Philadelphia (CHOP), families have access to advanced, multidisciplinary care, delivered by clinicians with deep expertise in leukodystrophies, all within a compassionate, family-centered environment.

Long-term outlook for children with multiple sulfatase deficiency

MSD is a progressive, life-limiting disease, with symptoms that worsen over time. However, there are treatments that can improve a child’s quality of life. CHOP is one of the premiere institutions for leukodystrophy care and a designated Center of Excellence. Our ongoing research efforts aim to enhance outcomes for children with MSD and offer families hope for the future of leukodystrophy care.