different enzyme needed to completely break down the heparan sulfate sugar chain. little clinical difference exists between these four types but symptoms appear most severe and seem to progress more quickly in children with type a. the average duration of sanfilippo syndrome is 8 to 10 years following onset of symptoms. most persons with mps iii live into their teenage years, and some live longer. sanfilippo a is the most severe of the mps iii disorders and is caused by the missing or altered enzyme heparan n-sulfatase. children with sanfilippo a have the shortest survival rate among those with the mps iii disorders. sanfilippo b is caused by the missing or deficient enzyme alpha-n-acetylglucosaminidase. sanfilippo c results from the missing or altered enzyme acetyl-coalpha-glucosaminide acetyltransferase. sanfilippo d is caused by the missing or deficient enzyme n-acetylglucosamine 6-sulfatase. the incidence of sanfilippo syndrome (for all four types combined) is about one in 70,000 births. mps iv mps iv, morquio syndrome, is estimated to occur in 1 in 700,000 births. its two subtypes result from the missing or deficient enzymes n-acetylgalactosamine-6-sulfatase (galns) (type a) or beta-galactosidase (type b) needed to break down the keratan sulfate sugar chain. clinical features are similar in both types but appear milder in morquio type b. onset is between ages 1 and 3. neurological complications include spinal nerve and nerve root compression resulting from extreme, progressive skeletal changes, particularly in the ribs and chest; conductive and/or neurosensitive loss of hearing and clouded corneas. intelligence is normal unless hydrocephalus develops and is not treated. physical growth slows generally around the age of 18 months, and stops completely by the age of 8. skeletal abnormalities include a bell-shaped chest, a flattening or curvature of the spine, shortened long bones, and dysplasia of the hips, knees, ankles, and wrists. the bones that stabilize the connection between the head and neck can be malformed (odontoid hypoplasia); in these cases, a surgical procedure called spinal cervical bone fusion can be lifesaving. restricted breathing, joint stiffness, and heart disease are also common. children with the more severe form of morquio syndrome may not live beyond their twenties or thirties. mps vi children with mps vi, maroteaux–lamy syndrome, usually have normal intellectual development but share many of the physical symptoms found in hurler syndrome. caused by the deficient enzyme n-acetylgalactosamine 4-sulfatase, maroteaux-lamy syndrome has a variable spectrum of severe symptoms. neurological complications include clouded corneas, deafness, thickening of the dura (the membrane that surrounds and protects the brain and spinal cord), and pain caused by compressed or traumatized nerves and nerve roots. growth is normal at first but stops suddenly around age 8. by age 10 children have developed a shortened trunk, crouched stance, and restricted joint movement. in more severe cases, children also develop a protruding abdomen and forward-curving spine. skeletal changes (particularly in the pelvic region) are progressive and limit movement. many children also have umbilical or inguinal hernias. nearly all children have some form of heart disease. an enzyme replacement therapy was tested on patients with mps vi and was successful in that it improved growth and joint movement. an experiment was then carried out to see whether an injection of the missing enzyme into the hips would help the range of motion and pain. mps vii mps vii, sly syndrome, one of the least common forms of the mucopolysaccharidoses, is estimated to occur in fewer than one in 250,000 births. the disorder is caused by deficiency of the enzyme beta-glucuronidase. in its rarest form, sly syndrome causes children to be born with hydrops fetalis, in which extreme amounts of fluid are retained in the body. survival is usually a few months or less. most children with sly syndrome are less severely affected. neurological symptoms may include mild to moderate intellectual disability by age 3, communicating hydrocephalus, nerve entrapment, corneal clouding, and some loss of peripheral and night vision. other symptoms include short stature, some skeletal irregularities, joint stiffness and restricted movement, and umbilical and/or inguinal hernias. some patients may have repeated bouts of pneumonia during their first years of life. most children with sly syndrome live into the teenage or young adult years. mps ix as of 2001, only one case of mps ix (online mendelian inheritance in man (omim): 601492) had been reported. the disorder results from hyaluronidase deficiency. symptoms included nodular soft-tissue masses located around joints, with episodes of painful swelling of the masses and pain that ended spontaneously within 3 days. pelvic radiography showed multiple soft-tissue masses and some bone erosion. other traits included mild facial changes, acquired short stature as seen in other mps disorders, and normal joint movement and intelligence. treatment currently there is no cure for these disorders. medical care is directed at treating systemic conditions and improving the person's quality of life. physical therapy and daily exercise may delay joint problems and improve the ability to move. changes to the diet will not prevent disease progression, but limiting milk, sugar, and dairy products has helped some individuals experiencing excessive mucus. surgery to remove tonsils and adenoids may improve breathing among affected individuals with obstructive airway disorders and sleep apnea. sleep studies can assess airway status and the possible need for nighttime oxygen. some patients may require surgical insertion of an endotrachial tube to aid breathing. surgery can also correct hernias, help drain excessive cerebrospinal fluid from the brain, and free nerves and nerve roots compressed by skeletal and other abnormalities. corneal transplants may improve vision among patients with significant corneal clouding. enzyme replacement therapy has proven useful in reducing non-neurological symptoms and pain. currently biomarin pharmaceutical produces enzyme replacement therapies for mps type i and vi. aldurazyme is an enzymatic replacement therapy for alpha-l-iduronidase produced by biomarin for use in type i mps. in may 2005, galsulfase, a recombinant enzyme replacement therapy also produced by biomarin was approved for mps vi (marateaux-lamy syndrome). in july 2006, the united states food and drug administration approved a synthetic version of i2s produced by shire pharmaceuticals group, called elaprase, as a treatment for mps type ii (hunter syndrome). vestronidase alfa (mepsevii) is a recombinant human lysosomal beta glucuronidase for mps vii (sly syndrome) approved in the united states in november 2017 (ultragenyx). bone marrow transplantation (bmt) and umbilical cord blood transplantation (ucbt) have had limited success in treating the mucopolysaccharidoses. abnormal physical characteristics, except for those affecting the skeleton and eyes, may be improved, but neurologic outcomes have varied. bmt and ucbt are high-risk procedures and are usually performed only after family members receive extensive evaluation and counseling.