Friday, May 14, 2010


Tomorrow, May 15, is MPS Awareness day.  

There is no cure for MPS. We hope that you might wear something purple tomorrow in honor of all of the children and adults fighting against MPS, in memory of those who are no longer with us, in support of research into new, safer and more effective treatment options, and eventually a cure.

There are six types and 12 subtypes of MPS, defined by which enzyme the body cannot produce or cannot produce in sufficient quantity to avoid build up of glycosaminoglycans (GAG).  In some respects we are lucky, Ethan has MPS I-Hurlers, and while there is no cure, bone marrow transplants and enzyme replacement therapy offer options that may allow him to live into adulthood and give him a somewhat normal life.  For other MPS kids and their families, there are no effective treatment options and their child's day to day life is difficult and their prognosis is grim.


We are fortunate that the MPS community is close knit. Though we might be on different paths depending on the type of MPS our loved one suffers from, we all stand in solidarity and support one another with love and understanding.


In recognition of MPS Awareness day, we wanted to take this opportunity to provide some information about the various MPS types to help raise awareness not just of Ethan's condition but of the different types and severities of MPS.  The information below, was copied from the national MPS Society, The Society for Mucopolysaccharide Diseases (UK) and Wikipedia.  These are complex and rare diseases, and Sarah and I are not experts.  If we've misrepresented anything, we hope that others in the MPS community will let us know so that we can correct it.


Thanks for being there for us and for helping us in supporting research for a cure!


Love,
Sarah, Todd, Caleb and Ethan


About MPS and Related Diseases
Mucopolysaccharidoses (MPS) and related diseases are genetic lysosomal storage diseases (LSD) caused by the body's inability to produce specific enzymes. Normally, the body uses enzymes to break down and recycle materials in cells. In individuals with MPS and related diseases, the missing or insufficient enzyme prevents the proper recycling process, resulting in the storage of materials in virtually every cell of the body. As a result, cells do not perform properly and may cause progressive damage throughout the body, including the heart, bones, joints, respiratory system and central nervous system. While the disease may not be apparent at birth, signs and symptoms develop with age as more cells become damaged by the accumulation of cell materials. 


MPS I
MPS 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


§  MPS I H (also called Hurler syndrome) (Ethan's type), is the most severe of the MPS 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.  Children with Hurler syndrome often die before age 10 from obstructive airway disease, respiratory infections, and cardiac complications. With ERT and bone marrow transplant Hurler's kids may live into adulthood


§  MPS I S, Scheie syndrome, is the mildest form of MPS 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.


§  MPS 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 mental retardation 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 MPS I H-S need continuous positive airway pressure during sleep to ease breathing. Life expectancy without enzyme replacement therapy and/or bone marrow transplant is generally into the late teens or early twenties.


Although no studies have been done to determine the frequency of MPS 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.


MPS I Treatment:  


·       MPS I H: Enzyme replacement therapy and bone marrow transplant can slow or stop further damage and can increase quality of life and extend lifespan.

·       MPS I H, H-S: Enzyme replacement therapy can slow or stop further damage and can increase quality of life and extend lifespan.

MPS II

MPS 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 mucopolysaccharidoses 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.


§  Children with MPS II A, the more severe form of Hunter syndrome, share many of the same clinical features associated with Hurler syndrome (MPS I H) but with milder symptoms. Onset of the disease is usually between ages 2 and 4. Developmental decline is usually noticed between the ages of 18 and 36 months, followed by progressive loss of skills. Other clinical features include coarse facial features, skeletal irregularities, obstructive airway and respiratory complications, short stature, joint stiffness, retinal degeneration (but no corneal clouding), communicating hydrocephalus, chronic diarrhea, enlarged liver and spleen, and progressive hearing loss. Whitish skin lesions may be found on the upper arms, back, and upper legs. Death from upper airway disease or cardiovascular failure usually occurs by age 15.


§  Physical characteristics of MPS II B are less obvious and progress at a much slower rate. Diagnosis is often made in the second decade of life. Intellect and social development are not affected. Skeletal problems may be less severe, but carpal tunnel syndrome and joint stiffness can restrict movement and height is somewhat less than normal. Other clinical symptoms include hearing loss, poor peripheral vision, diarrhea, and sleep apnea, although respiratory and cardiac complications can contribute to premature death. Persons with MPS II B may live into their 50s or beyond.


MPS II Treatment:
 In 2006, the FDA approved Elaprase as for enzyme replacement therapy (ERT). Current enzyme replacement therapies do not assist in arresting the neurological decline of Hunter's patients.

MPS III

MPS 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.


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 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.


Treatment:  There is no effective treatment for MPS III.  Support focuses on palliative care. 


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 (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 and often stops between the ages of 4-8. 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.

Treatment: As of today, there is no effective treatmenet for MPS IV. However, BioMarin began the first phase of a clinic trial for ERT for MPS IVA in 2009.

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, usually involving valve dysfunction.
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.


Treatment: Enzyme replacement therapy is available for individuals with MPS VI.


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 mental retardation 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.


Treatment: There has been little or no experience with bone marrow transplantation or with enzyme replacement therapy in individuals with MPS VII. Studies in animal models of this disease, however, suggest that both bone marrow transplantation and enzyme replacement therapy may be effective forms of therapy for problems affecting the body. 

Comments