Sly syndrome (MPS VII)

MPS VII is one of the mucopolysaccharidoses (MPS), a group of lysosomal storage disorders. Lysosomes are the parts of a cell that break down and recycle used material. In MPS VII, the enzyme beta-glucuronidase is missing or weak. Several kinds of long sugar chains called glycosaminoglycans (GAGs) cannot be broken down and build up in cells.

It is extremely rare. A 2024 review estimated that it affects fewer than 1 in 1 million people and makes up under 3 in 100 of all MPS diagnoses. It was first described in 1973 by Dr. William Sly and his colleagues.

Severity ranges widely. The most severe cases start before birth. Rare people with mild disease have lived into their forties.

MPS VII is caused by changes in both copies of the GUSB gene. This gene carries the instructions for making the beta-glucuronidase enzyme.

It is inherited in an autosomal recessive pattern. Each parent usually carries one changed copy and has no symptoms. When both parents are carriers, each child has a 1 in 4 chance of being affected.

It is not caused by anything a parent did, and it cannot be caught from another person. A genetic counselor can explain what test results mean for brothers, sisters and future pregnancies.

A feature that sets MPS VII apart is hydrops fetalis, a buildup of fluid in an unborn baby's body. In an international survey of 56 people with MPS VII, 23 had a history of hydrops. Most babies with this severe form are stillborn or die soon after birth. Some recover, and their later course can be mild or severe.

Other signs usually appear in infancy or early childhood. They include a large head, coarse facial features, a large tongue, a large liver and spleen, hernias and heart valve problems. Narrow airways can cause frequent infections and pauses in breathing during sleep (sleep apnea). The clear front of the eye (the cornea) can turn cloudy, and hearing loss is common.

Most people have short stature and bone changes. Stiff joints, hip problems and a curved spine are common, and a narrow spinal canal in the neck can press on the spinal cord. Many children have developmental delay and learning disability that get worse over time, but some people with MPS VII have normal intelligence.

MPS VII is sometimes first suspected before birth, when an ultrasound shows hydrops. It is among the lysosomal disorders most often found in babies with hydrops, so experts suggest testing for it. Before birth, the enzyme can be measured in cells from the placenta (chorionic villus sampling), from the fluid around the baby (amniotic fluid) or from cord blood.

After birth, doctors suspect it in a child with a large liver and spleen, hernias, coarse facial features, bone changes or developmental delay. Urine tests often show raised GAGs, though one normal result does not rule it out. The key test measures beta-glucuronidase activity in blood, white blood cells, skin cells or a dried blood spot.

A gene test of GUSB is usually done to confirm the diagnosis. It matters because some people have harmless gene changes that make the enzyme look low on lab tests (pseudodeficiency). MPS VII is not on the U.S. recommended newborn screening panel. Once a family's gene changes are known, relatives can be tested, and a later pregnancy can be tested early.

Vestronidase alfa (Mepsevii) is an enzyme replacement therapy. It is given by vein every two weeks, as an infusion of about four hours. The FDA approved it in 2017 for children and adults, and its U.S. label says its effect on the brain and spinal cord has not been determined. The European Union approved it in 2018 under exceptional circumstances, for problems outside the brain and nerves.

Because so few people have MPS VII, the main trial had only 12 patients. After 6 months, GAGs in the urine fell by 65%. In 11 of the 12, symptoms such as vision and movement problems improved or did not get worse. Severe allergic reactions (anaphylaxis) happened in 2 of 20 patients in the clinical program, so infusions are given where staff can treat them.

Supportive care is a large part of treatment. It includes surgery for hernias, hips and the spine, oxygen, antibiotics for infections and physical therapy. A 2022 review suggests check-ups about every 6 months, with tests once a year or as needed.

A donor stem cell transplant gives the body cells that make the enzyme, including cells that can work in the brain. For MPS VII, only about nine transplants had been described in medical reports by 2022, with mixed results. European transplant recommendations from 2025 say the decision is made for each person after expert evaluation.

Many families first meet MPS VII during pregnancy or at birth, when a baby has hydrops. For some, it brings grief very early. Because babies with hydrops are not always tested for MPS VII, some families learn the cause only after a second pregnancy is affected.

Children who survive the newborn period usually need many specialists for their bones, breathing, heart, eyes and hearing, and often for learning. Operations are common. In the 2016 survey, about 46% of people with the forms that begin in infancy or later had surgery. The most common operations were hernia repair, hip replacement and fusion of bones in the neck.

Enzyme therapy means a four-hour infusion every two weeks under medical supervision, for as long as it continues. Many people need help with daily activities. In the survey, most who could walk on their own lost that ability over time because of hip problems.

Very few people with MPS VII have had a transplant. When a specialist team does consider one, the cells come from another person. European transplant recommendations from 2025 rate it a clinical option for children, with the decision made after expert evaluation. That applies whether the donor is a matched brother or sister, a matched unrelated volunteer or a less closely matched donor.

Published cases used bone marrow and matched unrelated cord blood, and results were mixed. A Japanese woman transplanted at age 12 still had normal enzyme levels 22 years later, and her physical condition had stayed stable. Her intellectual disability, present before the transplant, did not improve. A girl with a moderate form, first transplanted at age 2, needed a second transplant. Six years later she had normal enzyme levels and normal development. Other children died of transplant complications or later illness.

Timing seems to matter most. Reviewers say a transplant can be considered as long as it happens before lasting damage to the brain and bones. A shortage of registry donors is not the main barrier for this condition. Joining a registry still helps the many other patients who need an unrelated donor.

Outlook varies widely. MedlinePlus Genetics says some people do not survive infancy, while others live into adolescence or adulthood. Babies with hydrops before birth have the hardest course. In the 2016 international survey, most babies whose hydrops began before birth died in early infancy, even if they survived the pregnancy. The causes were heart, kidney or breathing failure. Rare people with mild disease have lived into their forties.

Having had hydrops does not by itself predict how severe the disease will be later. In the same survey, 13 of the 23 people who had hydrops survived childhood, with disease ranging from mild to severe. Heart disease and blocked airways are major causes of death.

Enzyme therapy lowers GAG levels, and in small studies it improved or stabilized symptoms. In a group of 9 patients from Spain and Portugal, those diagnosed early and treated in a timely way generally did better.