Articles / Journals
Wood, Heather. “Gene therapy for mucopolysaccharidosis shows promise.” (2017): 512-512. Access from Nature.com
What is Mucopolysaccharidosis ?
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What is Mucopolysaccharidosis?
Mucopolysaccharidosis (MPS) is caused by a defect in one of the lysosomal enzymes leading to improper breakdown of mucopolysaccharides (long chains of sugar molecules found in the body). Due to this improper breakdown, these sugars buildup in cells, blood, skeleton, arteries connective tissue. Sugar buildup is also found in vital organs like the liver, spleen, respiratory system, central nervous system and bone marrow. This accumulation causes damage to cells, tissues and organs subsequently affecting organ and system functions.
Across the globe, MPS affects 1 in every 25,000 persons. MPS occurs equally among males and females.
- MPS 1 H – is the severest type of mucopolysaccharidosis. It is caused by a deficiency of the enzyme alpha-L-iduronidase. This causes an excess accumulation of dermatan and heparan sulfates. This disorder presents itself in the first six months of life. Babies experience developmental delays, recurrent respiratory and urinary infections, noisy breathing, clouding cornea in the eye, spine deformities and other joint issues. Mental regression usually occurs after the age of two.
Scheie syndrome (mucopolysaccharidosis type I-S; MPS 1-S) is the mildest type of mucopolysaccharidosis. People with Scheie syndrome lack an enzyme known as alpha-L-iduronidase. Affected people usually have normal height, development, intelligence and life expectancy.
- MPS I H/S (Hurler-Scheie syndrome) – is extremely rare and affected individuals have a less severe form of Hurler syndrome, but a more severe form of Scheie syndrome. Affected individuals are usually diagnosed between the ages three to six years. They may present with enlargement of the spleen and liver, coarse facial features, short stature, joint stiffness, other skeletal issues, clouding corneas and mild developmental delays.
- MPS II-(Hunter syndrome) – this is the only type of MPS which is X-linked and inherited from the mother. Symptoms appear around the age of two and children present with short stature, joint stiffness, skeletal issues, coarse facial features, macrocephaly (large head), short neck and broad chest, hearing loss, liver and spleen enlargement. In the milder type of MPS IIB, individual intelligence may be slightly affected but in the severe type of MPS IIA intellectual disability may be severe.
- MPS III A, B, C, and D (Sanfillipo syndrome) – has four subtypes which are A, B, C and D caused by different enzyme deficiencies. Early signs include developmental delays like crawling, sitting up or walking, sleeplessness and hyperactivity. All types of Sanfillipo syndrome present with different degrees of intellectual delays, loss of skills like language and fine motor skills and hearing loss. Eventually some individuals lose the ability to walk and perform daily activities.
- MPS IV A and B (Morquio syndrome) has two subtypes Morquio syndrome A and B. Morquio is due to a deficiency of the enzyme N-acetyl-galactosamine-6-sulfatase and beta-galactosidase, leading to an accumulation of keratan and chondroitin sulfate in type A and keratan sulfate in type B. Most affected people have normal intelligence. The subtype MPS IV B is milder than MPS IV A. Common symptoms include short neck, stunted growth and short stature, knock knees, curvature of the spine and broad chest. In most cases of MPS IV A, people experience difficulties with mobility and daily activities.
- MPS VI (Maroteaux-Lamy syndrome) – is due to a deficiency in the enzyme N-acetylgalactosamine-4-sulfatase leading to an accumulation of dermatan sulfate. The severity varies among affected individuals with some presenting with a mild form while others may be more severe. Common signs include coarse facial features, prominent chest, clouding corneas, umbilical hernia, enlargement of liver and spleen, skeletal issues and cardiac abnormalities. In most cases, intelligence is unaffected.
- MPS VII (Sly syndrome) – is due to a deficiency in the enzyme beta-glucuronidase leading to an accumulation of three glycosaminoglycans: dermatan sulfate, heparan sulfate and chondroitin sulfate. Again symptoms vary among individuals. Some may present with intellectual disability while others are unaffected. Common signs include coarse facial features, prominent chest, clouding corneas, umbilical hernia, enlargement of liver and spleen, skeletal issues and cardiac abnormalities. In rare cases, infants present with accumulation of fluid in various tissues of the body (hydrops fetalis).
- MPS IX (hyaluronidase deficiency) – is a very rare type of MPS due to a deficiency in the enzyme hyaluronidase needed to breakdown the mucopolysaccharides – hyaluronan (hyaluronic acid). Symptoms include short stature, frequent ear infections and abnormal soft tissue masses.
Symptoms usually appear in infancy or early childhood. Signs and symptoms of MPS can be grouped into the following categories. These include:
- Musculoskeletal abnormalities – short stature, stiff joints
- Facial features – coarse features, flat nose, thick lips
- Respiratory issues – frequent bronchial infections, sleep apnea, obstructed airways
- Cardiovascular issues – valve dysfunction, hypertension, congestive heart disease
- Ophthalmologic issues – corneal clouding, glaucoma, retinal degeneration
- Hearing – progressive deafness
- Neurological – hydrocephalus, spinal issues
- biochemical tests – serum assays for lysosomal enzymes
- urinalysis – to test for abnormal excretion of glycosaminoglycans
- molecular test – DNA tests like Next Generation Sequencing (NGS) to locate the exact mutation causing the form of MPS.
- laronidase (Aldurazyme) for MPS I. This is approved for Hurler and Hurler-Scheie types of MPS I. The drug is manufactured by BioMarin and distributed by Sanofi Genzyme
- idursulfase (Elaprase) for MPS II. The drug is manufactured by Shire
- elosufase alfa (Vimizin) for MPS IVA. The drug is a product of BioMarin
- galsulfase (Naglazyme) for MPS VI – Maroteaux-Lamy syndrome. The drug is a product of BioMarin
If there is a known case of MPS in the family, it is absolutely essential for closest female relatives like siblings, uncles, aunts and cousins to test for carrier status.
If a woman with a carrier status is pregnant, prenatal test is essential to determine if the fetus has the disease mutation.