Diagnosis often can be made through clinical examination and urine tests (excess mucopolysaccharides are excreted in the urine). Enzyme assays (testing a variety of cells or body fluids in culture for enzyme deficiency) are also used to provide definitive diagnosis of one of the<unk> . Prenatal diagnosis using amniocentesis and chorionic villus sampling can verify if a fetus either carries a copy of the defective gene or is affected with the disorder. Genetic counseling can help parents who have a family history of the<unk>  determine if they are carrying the mutated gene that causes the disorders. Types Seven distinct clinical types and numerous subtypes of the<unk>  have been identified. Although each<unk>  <unk>  differs clinically, most patients generally experience a period of normal development followed by a decline in physical and/or mental function. (Note:<unk> -V and<unk> -VIII are no longer in use as designations for any disease.) Overview table + Main<unk>  Type Common nameOther names OMIM Gene Locus Deficient enzyme Accumulated products Symptoms Incidence<unk>  IH Hurler syndrome IDUA 4p16.3 α-L-iduronidase Heparan sulfateDermatan sulfate Intellectual disability, micrognathia, coarse facial features, macroglossia, retinal degeneration, corneal clouding, cardiomyopathy, hepatosplenomegaly 1:100,000<unk>  IH/S Hurler–Scheie syndrome<unk>  IS Scheie syndromeFormerly:<unk>  type V<unk>  II Hunter syndrome IDS Xq28 Iduronate sulfatase Heparan sulfateDermatan sulfate Intellectual disability (similar, but milder, symptoms to<unk>  I). This type exceptionally has X-linked recessive inheritance 1:100,000-1:150,000 males<unk>  IIIA Sanfilippo syndrome ASulfamidase deficiency SGSH 17q25.3 Heparan sulfamidase Heparan sulfate Developmental delay, severe hyperactivity, spasticity, motor dysfunction, death by the second decade 1:280,000 – 1:50,000<unk>  IIIB Sanfilippo syndrome BNAGLU deficiency NAGLU 17q21.2 N-acetylglucosaminidase<unk>  IIIC Sanfilippo syndrome C HGSNAT 8p11.21 Heparan-α-glucosaminide N-acetyltransferase<unk>  IIID Sanfilippo syndrome D GNS 12q14.3 N-acetylglucosamine 6-sulfatase<unk>  IVA Morquio syndrome A GALNS 16q24.3 Galactose-6-sulfate sulfatase Keratan sulfateChondroitin 6-sulfate Severe skeletal dysplasia, short stature, motor dysfunction 1 in 75,000<unk>  IVB Morquio syndrome B GLB1 3p22.3 β-galactosidase Keratan sulfate<unk>  V See<unk>  IS (Scheie syndrome) above<unk>  VI Maroteaux–Lamy syndromeARSB deficiency ARSB 5q14.1 N-acetylgalactosamine-4-sulfatase Dermatan sulfate Severe skeletal dysplasia, short stature, motor dysfunction, kyphosis, heart defects<unk>  VII Sly syndromeGUSB deficiency GUSB 7q11.21 β-glucuronidase Heparan sulfateDermatan sulfateChondroitin 4,6-sulfate Hepatomegaly, skeletal dysplasia, short stature, corneal clouding, developmental delay Hyaluronidase deficiency HYAL1 3p21.31 Hyaluronidase Hyaluronic acid Nodular soft-tissue masses around joints, episodes of painful swelling of the masses, short-term pain, mild facial changes, short stature, normal joint movement, normal intelligence<unk>  I<unk>  I is divided into three subtypes based on severity of symptoms. All three types result from an absence of, or insufficient levels of, the enzyme alpha-L-iduronidase. Children born to an<unk>  I parent carry the defective gene. *<unk>  I H (also called Hurler syndrome or α-L-iduronidase deficiency), is the most severe of the<unk>  I subtypes. Developmental delay is evident by the end of the first year, and patients usually stop developing between ages 2 and 4. This is followed by progressive mental decline and loss of physical skills. Language may be limited due to hearing loss and an enlarged tongue. In time, the clear layers of the cornea become clouded and retinas may begin to degenerate. Carpal tunnel syndrome (or similar compression of nerves elsewhere in the body) and restricted joint movement are common. : Affected children may be quite large at birth and appear normal but may have inguinal (in the groin) or umbilical (where the umbilical cord passes through the abdomen) hernias. Growth in height may be faster than normal but begins to slow before the end of the first year and often ends around age 3. Many children develop a short body trunk and a maximum stature of less than 4 feet. Distinct facial features (including flat face, depressed nasal bridge, and bulging forehead) become more evident in the second year. By age 2, the ribs have widened and are oar-shaped. The liver, spleen, and heart are often enlarged. Children may experience noisy breathing and recurring upper respiratory tract and ear infections. Feeding may be difficult for some children, and many experience periodic bowel problems. Children with Hurler syndrome often die before age 10 from obstructive airway disease, respiratory infections, and cardiac complications. *<unk>  I S, Scheie syndrome, is the mildest form of<unk>  I. Symptoms generally begin to appear after age 5, with diagnosis most commonly made after age 10. Children with Scheie syndrome have normal intelligence or may have mild learning disabilities; some may have psychiatric problems. Glaucoma, retinal degeneration, and clouded corneas may significantly impair vision. Other problems include carpal tunnel syndrome or other nerve compression, stiff joints, claw hands and deformed feet, a short neck, and aortic valve disease. Some affected individuals also have obstructive airway disease and sleep apnea. Persons with Scheie syndrome can live into adulthood. *<unk>  I H-S, Hurler–Scheie syndrome, is less severe than Hurler syndrome alone. Symptoms generally begin between ages 3 and 8. Children may have moderate intellectual disability and learning difficulties. Skeletal and systemic irregularities include short stature, marked smallness in the jaws, progressive joint stiffness, compressed spinal cord, clouded corneas, hearing loss, heart disease, coarse facial features, and umbilical hernia. Respiratory problems, sleep apnea, and heart disease may develop in adolescence. Some persons with<unk>  I H-S need continuous positive airway pressure during sleep to ease breathing. Life expectancy is generally into the late teens or early twenties. Although no studies have been done to determine the frequency of<unk>  I in the United States, studies in British Columbia estimate that 1 in 100,000 babies born has Hurler syndrome. The estimate for Scheie syndrome is one in 500,000 births and for Hurler-Scheie syndrome it is one in 115,000 births.<unk>  II<unk>  II, Hunter syndrome or iduronate sulfatase deficiency, is caused by lack of the enzyme iduronate sulfatase. Hunter syndrome has two clinical subtypes and (since it shows X-linked recessive inheritance) is the only one of the<unk>  in which the mother alone can pass the defective gene to a son. The incidence of Hunter syndrome is estimated to be 1 in 100,000 to 150,000 male births.<unk>  III<unk>  III, Sanfilippo syndrome, is marked by severe neurological symptoms. These include progressive dementia, aggressive behavior, hyperactivity, seizures, some deafness and loss of vision, and an inability to sleep for more than a few hours at a time. This disorder tends to have three main stages. During the first stage, early mental and motor skill development may be somewhat delayed. Affected children show a marked decline in learning between ages 2 and 6, followed by eventual loss of language skills and loss of some or all hearing. Some children may never learn to speak. In the syndrome's second stage, aggressive behavior, hyperactivity, profound dementia, and irregular sleep may make children difficult to manage, particularly those who retain normal physical strength. In the syndrome's last stage, children become increasingly unsteady on their feet and most are unable to walk by age 10. Thickened skin and mild changes in facial features, bone, and skeletal structures become noticeable with age. Growth in height usually stops by age 10. Other problems may include narrowing of the airway passage in the throat and enlargement of the tonsils and adenoids, making it difficult to eat or swallow. Recurring respiratory infections are common. There are four distinct types of Sanfilippo syndrome, each caused by alteration of a 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<unk>  III live into their teenage years, and some live longer. * Sanfilippo A is the most severe of the<unk>  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<unk>  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.<unk>  IV<unk>  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
Mucopolysaccharidosis
Hunter syndrome
Gangliosidosis
Mucopolysaccharidosis type I
Glycogen storage disease
Hurler syndrome
Sphingolipidoses
Maroteaux–Lamy syndrome