Multiple Sulfatase Deficiency

Multiple sulfatase deficiency is a complex, inherited disorder caused by a genetic mutation. The condition results in the dysfunction of specialized proteins known as enzymes responsible for the breakdown of certain sugars and fats in the body. As a result, these sugar and fat molecules accumulate to toxic levels in many of the body’s tissues and organ systems, especially the central nervous and skeletal systems. Because the disease affects different children at many different stages, multiple sulfatase deficiency is often classified as “neonatal,” “late-infantile,” or “juvenile.” Multiple sulfatase deficiency is one of about 50 diseases classified as lysosomal storage disorders (LSD).

Lysosomes contain specific proteins (enzymes) responsible for breaking down and recycling molecules such as fats and sugars. Individuals with a lysosomal storage disorder lack one of these necessary enzymes or do not have one of these enzymes in sufficient quantities to break down molecules for proper cell function.

Timing of symptoms depend on whether a child has neonatal, late-infantile, or juvenile multiple sulfatase deficiency. Symptoms may include:

• Seizures
• Developmental delay
• Movement problems
• Loss of developmental skills (developmental regression)
• Dry, scaly skin (ichthyosis)
• Excess hair growth (hypertrichosis)
• Skeletal abnormalities
• Distinct facial features (coarse facial features)
• Enlarged liver or spleen (hepatosplenomegaly)

Multiple sulfatase deficiency is caused by mutations in the SUMF1 gene, which contains instructions for the production of an enzyme called formylglycine-generating enzyme (FGE). This enzyme is responsible for the modification of many other enzymes known as sulfatases. Sulfatases are located in the lysosomes of a cell and work to break down complex sugars and fats. Mutations in the SUMF1 gene result in lack of properly functioning FGE, which in turn leads to deficient production of sulfatase enzymes. This deficiency causes the abnormal accumulation of fats and sugars broken down by sulfatases in properly functioning cells, eventually leading to signs of disease.

This genetic condition is inherited in an autosomal recessive pattern. This means that an affected child has received one defective copy of the SUMF1 gene from each of their parents.

There are currently no approved therapies that reverse the effects of multiple sulfatase deficiency. Current approaches to multiple sulfatase deficiency involve interdisciplinary collaboration to provide supportive therapies and targeted management for specific symptoms.

At the Boston Children’s Lysosomal Storage Disorder (BoLD) Program, our team of providers is committed to the care of complex patients. As part of Boston Children’s Hospital, we are prepared to meet the challenge of providing multifaceted care by partnering with you and your child to deliver direct care in our BoLD clinic. We work with the broad array of world-class specialists at Boston Children’s to optimize the care we provide your child with multiple sulfatase deficiency.