HURLERS SYNDROME

Mucopolysaccharidosis (MPSs) are a family of metabolic disorders caused by the deficiency of lysosomal enzymes needed to degrade glycoaminoglycan (GAG). GAG is an important part of extracellular matrix, joined fluid and connective tissue throughout the body. When the GAG is in excess in the cells there might be an ineffective in terms of the cells function and metabolism. The sites of the disease depend on the specific of enzyme deficiency in an area. It is classified according to its severity.

Background: Hurler syndrome is the most common type of MPS disease. It is rarely hereditary (autosomal recessive) or congenital. Onset takes place in infants aged 6 to 12 months. An affected child may appear normal in about a year but soon the head of a child grows bigger than normal. The occurrence of this is about 1:10,000 for male and female. Usually the child dies before 10 years of age. This condition was first observed by John Thomson in 1900 where Professor von Pfaundler of Munich Peadiatric Society works was basis for the study. The term Hurler Syndrome was called gargoylism or lipochondrodystrophy. It came from Gertrud Hurler, a German pediatrician and a medical practitioner. Fredrick Parker Weber concurred the diagnoses of gorgoylism. It is now called Hurler or MPS I. Mucopolysaccharides is categorized as MPS I H (Hurler Syndrome), MPS I H-S (Hurler-Scheie Syndrome) and MPS I S(Scheie Syndrome).

Description and Causes: Hurler Syndrome is one of a group of inherited metabolic storage disorders in which they lack an enzyme which affects the various organs and tissues including the brain. It is a deficiency of alpha-L-iduronidase (IDUA) which is responsible for regulating the amount of heparin sulfate and derman sulfate by the process of degredation of mucopolysaccharides in lysosome. The said enzyme breaks down complex sugars such as glycoaminoglycans. The process is essential for normal growth and homeostasis of tissue. It is also used to build tissues and bones.

Symptoms: Hurler syndrome most often appear between ages 3 and 8. Infants with severe Hurler syndrome appear normal at birth. Facial symptoms may become more noticeable during the first 2 years of life. And if the disease is not stopped, children with Hurlers Syndrome may die by 5 to 10 years of age. Symptoms include: Abnormal bones in the spine Claw hand Cloudy corneas, degenerated retinas Deafness (hearing problems and frequent ear infection) Halted growth (dwarfism)

Heart value problems including the changes in valves Joint disease (includes stiffness), deformed bones in spine, hips, knees, wrist and fingers Mental retardation that gets worse over time Thick, coarse facial features with low nasal bridge (enlarged tongue) Enlarged spleen, liver and heart Obstructive airway disease and respiratory infections

Diagnosis: Tests doctors may use to diagnose Hurler's syndrome include: 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 mucopolysaccharidoses. 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 mucopolysaccharidoses determine if they are carrying the mutated gene that causes the disorders. Tests of blood and/or skin samples to see if the body is making the IDUA enzyme Genetic tests for mutations to the gene for the IDUA enzyme X-rays to check for damage to the spine Electrocardiogram (EKG) or echocardiogram to check heart function and valve problems

Treatment: The goal of treatment for Hurler's syndrome is to give the body the missing enzyme so it can break down GAGs. The two main treatments for children with Hurler's syndrome are: Enzyme replacement therapy: The BioMarin Pharmaceutical manufactures laronidase in replacement for the missing enzyme. It is proven to be useful in reducing a nonneurological symptoms and pain. Bone marrow Transplantation (BMT) or cord blood transplant (CBT): Abnormal physical characteristics, except for those affecting the skeleton and eyes, can be improved, and neurologic degeneration can often be halted. BMT and UCBT are high-risk procedures with high rates of morbidity and mortality. Usually there is no cure but a certain number of people who used these methods and it have a mixed result in persons with Hurler. With the new advances in technologies the researchers are still studying for a gene therapy as a mode of treatment which they still have to test in humans.

References: http://marrow http://www.nlm.nih.gov/medlineplus/ency/article/001204.htm http://www.mpssociety.org. http://marrow.org/Patient/Disease_and_Treatment/About_Your_Disease/Metabolic_Diso rders/Hurler_s_Syndrome.aspx http://www.disabled-world.com/disability/hurler-syndrome.php

Children with Hurlers Syndrome

Child with a Hurler Syndrome at an age of 1 year showing no signs of the disorder yet.

Hurler Syndrome patient but with a slight enlargement of the head.

At an early stage, the signs and symptoms of Hurler Syndrome appears.

The bulge of the eye, depressed nasal bridge and facial features became evident.

Hurlers Syndrome Pictures

The normal and deformed nasal bridge of a child with Hurler Syndrome

The heart of a patient with Hurler Syndrome

The different faces of a patient at certain age having the said syndrome, Hurler