Hurler syndrome; Hurler syndrome ... (Mucopolysaccharidosis type I, Hurler syndrome, Hurler-Scheie syndrome, Scheie syndrome) - Gen IDUA.
Mucopolysaccharidoses encompass a group of inherited metabolic diseases caused by the absence or malfunction of certain necessary for processing glycosaminoglycans, found in bone, cartilage, tendons, corneas, skin and connective tissue enzymes. The glycosaminoglycans, formerly known as mucopolysaccharides, are also present in the synovial fluid of the joints. People suffering from mucopolysaccharidosis not encode sufficient quantities of one of the eleven enzymes required to transform glycosaminoglycans in protein and simpler molecules, or encode enzymes that do not work properly. Over time, these glycosaminoglycans accumulate in cells, blood and connective tissues. This produces permanent and progressive cellular damage that affect the appearance and physical abilities, organs and body functions of the individual and, in most cases, mental development.
Mucopolysaccharidosis type I (MPS I) is a disease that affects many parts of the body. At the time, the disease was divided into three separate syndromes: Hurler syndrome (MPS IH), the Hurler-Scheie (MPS IH / S) and Scheie syndrome (MPS IS), which correspond to three types of higher to lower. Because of the overlap between each of these three syndromes, currently the Hurler syndrome is divided into major and minor types.
Often, children with MPS I have no signs or symptoms of the disease at birth, although some have umbilical hernia or inguinal hernia. People with MPS I severe type usually begin to show other signs and symptoms of the disease in the first year of life, while those with the milder form have milder features that manifest during childhood.
Signs and symptoms of the disease may include microcephaly, hydrocephalus, abnormal heart valves, hepatosplenomegaly and macroglossia. The vocal cords are also enlarged, which leads to severe hoarse voice. In addition, the narrowing of the airways causes frequent respiratory infections and sleep apnea. Other signs and symptoms may include corneal opacity which can cause significant loss of vision, recurrent ear infections , and hearing loss, short stature, joint deformities, multiple dysostosis, thoracic-lumbar kyphosis, carpal tunnel syndrome, spinal stenosis in the neck that can compress and damage the spinal cord and progressive enlargement of facial features.
Although both forms of MPS I can affect many different organs and tissues, people with severe MPS I have decreased intellectual function and a faster progression of the disease. In these individuals, developmental delay is usually present before one year of age, and those severely affected eventually lose basic functional skills. In general, these individuals have a lower life expectancy and do not survive beyond the second childhood. For its part, individuals with mild MPS usually live into adulthood and may or may not have a shorter lifespan. Some people with type dimmed have learning disabilities, while others show no intellectual deficits. Heart disease and obstruction of the airways are major causes of death in people with both types of MPS I.
This process is due to mutations in the gene IDUA (iduronidase, alpha-L-), located on the short arm of chromosome 4 (4p16.3). This gene encodes an enzyme called alpha-L-iduronidase, essential for the breakdown of glycosaminoglycans (GAGs). Through hydrolysis, the alpha-L-iduronidase used to decompose water molecules alpha-L-iduronic acid unsulphated, which is present in two GAGs called heparan sulfate and dermatan sulfate. Alpha-L-iduronidase is in lysosomes.
Have identified at least 199 mutations in the gene corresponding to IDUA: missense mutations (112), and cutting mutations -splicing- junction (33), regulatory mutations (1), small deletions (30), small insertions (15 ), small indels (1), larger deletions (4) and complex rearrangements (3). The most common mutations change nucleotides. All mutations reduce or completely eliminate the function of alpha-L-iduronidase. People who do not encode any alpha-L-iduronidase have the severe form of this disease. Deficiency activity of alpha-L-iduronidase enzyme leads to the accumulation of heparan sulfate and dermatan sulfate in the lysosomes. The accumulation of these GAGs increases the size of lysosomes, so many tissues and organs are enlarged. Furthermore, it is likely that the accumulated GAGs may interfere with functions of other proteins in lysosomes and alter the movement of molecules within the cell.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with Hurler syndrome (MPS I), by complete PCR amplification of exons IDUA gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).