Sly syndrome, also called

mucopolysaccharidosis Mucopolysaccharidoses are a group of metabolic disorders caused by the absence or malfunctioning of lysosomal enzymes needed to break down molecules called glycosaminoglycans (GAGs). These long chains of sugar carbohydrates occur within the cel ...

type VII (MPS-VII), is an

autosomal recessive In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the Phenotype, effect of a different variant of the same gene on Homologous chromosome, the other copy of the chromosome. The firs ...

lysosomal storage disease caused by a deficiency of the

enzyme An enzyme () is a protein that acts as a biological catalyst by accelerating chemical reactions. The molecules upon which enzymes may act are called substrate (chemistry), substrates, and the enzyme converts the substrates into different mol ...

β-glucuronidase. This enzyme is responsible for breaking down large sugar molecules called

glycosaminoglycan Glycosaminoglycans (GAGs) or mucopolysaccharides are long, linear polysaccharides consisting of repeating disaccharide units (i.e. two-sugar units). The repeating two-sugar unit consists of a uronic sugar and an amino sugar, except in the case o ...

s (AKA GAGs, or mucopolysaccharides). The inability to break down GAGs leads to a buildup in many tissues and organs of the body. The severity of the disease can vary widely.

Signs and symptoms

The most severe cases of Sly syndrome can result in

hydrops fetalis Hydrops fetalis or hydrops foetalis is a condition in the fetus characterized by an accumulation of fluid, or edema, in at least two fetal compartments. By comparison, hydrops allantois or hydrops amnion is an accumulation of excessive fluid in ...

, which results in

fetal A fetus or foetus (; : fetuses, foetuses, rarely feti or foeti) is the unborn offspring of a viviparous animal that develops from an embryo. Following the embryonic stage, the fetal stage of development takes place. Prenatal development is a ...

death or death soon after birth. Some people with Sly syndrome may begin to have symptoms in early childhood. Symptoms can include an enlarged head, fluid buildup in the brain, coarse facial features, enlarged tongue, enlarged liver,

enlarged spleen Splenomegaly is an enlargement of the spleen. The spleen usually lies in the left upper quadrant (LUQ) of the human abdomen. Splenomegaly is one of the four cardinal signs of ''hypersplenism'' which include: some reduction in number of circulatin ...

, problems with the

heart valve A heart valve is a biological one-way valve that allows blood to flow in one direction through the chambers of the heart. A mammalian heart usually has four valves. Together, the valves determine the direction of blood flow through the heart. Hea ...

s, and abdominal

hernia A hernia (: hernias or herniae, from Latin, meaning 'rupture') is the abnormal exit of tissue or an organ (anatomy), organ, such as the bowel, through the wall of the cavity in which it normally resides. The term is also used for the normal Devel ...

s. People with Sly syndrome may also have

sleep apnea Sleep apnea (sleep apnoea or sleep apnœa in British English) is a sleep-related breathing disorder in which repetitive Apnea, pauses in breathing, periods of shallow breathing, or collapse of the upper airway during sleep results in poor vent ...

, frequent lung infections, and problems with vision secondary to cloudy

cornea The cornea is the transparency (optics), transparent front part of the eyeball which covers the Iris (anatomy), iris, pupil, and Anterior chamber of eyeball, anterior chamber. Along with the anterior chamber and Lens (anatomy), lens, the cornea ...

s. Sly syndrome causes various musculoskeletal abnormalities that worsen with age. These can include short stature, joint deformities, dysostosis multiplex,

spinal stenosis Spinal stenosis is an abnormal narrowing of the spinal canal or neural foramen that results in pressure on the spinal cord or nerve roots. Symptoms may include pain, numbness, or weakness in the arms or legs. Symptoms are typically gradual in ...

, and

carpal tunnel syndrome Carpal tunnel syndrome (CTS) is a nerve compression syndrome associated with the collected signs and symptoms of Pathophysiology of nerve entrapment#Compression, compression of the median nerve at the carpal tunnel in the wrist. Carpal tunn ...

. While some individuals have developmental delay, others may have normal intelligence. However, the accumulation of GAGs in the brain usually leads to the slowing of development from ages 1–3, and then a loss of previously learned skills until death.

Genetics

The defective gene responsible for Sly syndrome is located on chromosome 7.

Diagnosis

Most people with Sly disease will have elevated levels of GAGs seen in the urine. A confirmatory test is necessary for diagnosis. Skin cells and

red blood cell Red blood cells (RBCs), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

s of affected people will have low levels of β-glucuronidase activity. Sly syndrome can also be diagnosed through

prenatal testing Prenatal testing is a tool that can be used to detect some birth defects at various stages prior to birth. Prenatal testing consists of prenatal screening and prenatal diagnosis, which are aspects of prenatal care that focus on detecting problem ...

Treatment

Vestronidase alfa-vjbk (trade name Mepsevii), an enzyme replacement therapy which is a recombinant form of human β-glucuronidase, is approved by U.S. Food and Drug Administration for the treatment of Sly syndrome. Hematopoietic stem cell transplant (HSCT) has been used to treat other types of MPS diseases, but this is not yet available for MPS-VII. Animal experiments suggest that HSCT may be an effective treatment for MPS-VII in humans.

Prognosis

The life expectancy of individuals with MPS VII varies depending on the symptoms. Some individuals are stillborn, while some may survive into adulthood.

Epidemiology

MPS-VII is one of the rarest forms of MPS. It occurs in less than 1 in 250,000 births. As a family, MPS diseases occur in 1 in 25,000 births, and the larger family of lysosomal storage diseases occur in 1 out of 7,000 to 8,000 births.

History

Sly syndrome was originally discovered in 1972. It was named after its discoverer William S. Sly, an American biochemist.

References

{{Mucopolysaccharidoses Proteoglycan metabolism disorders Autosomal recessive disorders Syndromes Rare diseases Skin conditions resulting from errors in metabolism Diseases named after discoverers