Hurler's Syndrome

Metabolism of the human body is the set of chemical processes and reactions, that occur between the various components in the body, and is necessary to maintain life. Enzymes play a key role in human metabolism, as they speed up or catalyze the processes. The lack or excess of an enzyme, plays an important role in an individual's well-being. In this article, we take a detailed look at Hurler's syndrome facts, an inherited disorder, caused by the lack of enzyme, and its symptoms and complications.

What is Hurler's Syndrome?
It is a rare genetic disorder, in which a person's metabolism is affected by the deficiency of an enzyme called lysosomal alpha-L-iduronidase. This enzyme is responsible for the breaking down of long chains of sugar molecules called glycosaminoglycans, so they can be discarded by the body. These molecules are located in different areas of the human body, and can also be found in mucus and the fluid surrounding joints. Without the enzyme, the sugar molecules collect and bind together in the body. Their excessive presence in the body damages vital organs like the heart, and causes permanent and progressive damage to a person's mentality, organ function and health, physical abilities and appearance.

Hurler's syndrome is also called mucopolysaccharidosis type I (MPS I), Hurler's disease, and gargoylism. It belongs to a class of diseases called mucopolysaccharidoses or MPS. MPS1 is divided into 3 subtypes, based on severity of symptoms, the most severe being Hurler's syndrome. MPS1 S (Scheie syndrome) and MPS1 H-S (Hurler-Scheie syndrome) are the 2 other types. Hurler's syndrome was identified in 1919 by Dr. Gertrud Hurler. This syndrome occurs in 1 in every 100,000 births. The child inherits the defective gene from both parents. The parents may have one copy of the gene, but the child inherits two and hence this syndrome occurs.

Symptoms
It is difficult to detect this syndrome at birth. Facial differences may become apparent during the first 2 years of childhood. The appearance of the symptoms in a child is usually between the ages of three and eight. Signs of Hurler's syndrome are:

• Cloudy corneas
• Deafness
• Stunted growth
• Abnormal spinal bones
• Claw hand
• Joint abnormalities and stiffness
• Flat appearance of the bridge of the nose (low nasal bridge)
• Abnormal heart valves
• Protruding abdomen
• Thick, coarse facial features, with abundant hair
• Mental retardation, which worsens with age

There are numerous complications caused by Hurler's syndrome, due to the accumulation of sugar molecules. The neurology and behavior of a child is affected, learning skills are hindered and deteriorate with age. The respiratory system is compromised, as mucus thickens and blocks the breathing passages. Heavy or strained breathing is common, along with enlarged tonsils. Children suffering from this syndrome have serious circulatory system problems. The heart valves and aorta are thick and enlarged, leading to heart failure. Due to most of the above complications, the average lifespan for a child affected with Hurler's syndrome is just 10 years.

Diagnosis
Blood and urine testing is the most accurate indicator. EKGs and X-rays are carried out to verify heart and spine complications. Amniocentesis is a prenatal procedure performed to see if the fetus is carrying the defective gene or is affected with the disorder. Genetic testing is used to determine if an individual has the defective gene, and the chance that his offspring may be affected. Both Amniocentesis and genetic testing is recommended for families with a history of MPS1 disorders.

Treatment & Prognosis
The outlook for Hurler's syndrome is bleak. No cure or remedy exists yet. Treatment is limited to relieving symptoms, treating the complications, and ensuring quality of life. Enzyme replacement therapy is one method, where a substitute enzyme, laronidase, is given. This does not cure the disorder but helps ease pain and curb symptoms. Bone marrow transplantation is a form of treatment where defective cells are replaced by enzyme producing cells. But this treatment is high risk and has mixed results. Research is being conducted on using gene therapy as a possible treatment. But it is still in the experimental stage.

Due to different areas that are affected by this disorder, a variety of specialists must be involved in the care and treatment. Limiting intake of sugar and milk products helps in reducing mucus levels. Physical therapy helps in easing some of the pain associated with joint problems. But each case of Hurler's syndrome is unique and highly individual, so orthopedics and physical therapists must be consulted for guidance. The National MPS society provides up-to-date information and help for parents of Hurler's syndrome children.