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Management of children with mucopolysaccharidosis type I in Croatia

Mucopolysacchridosis type I (MPS I) is a rare inherited metabolic disorder due to the deficiency of the lysosome enzyme alpha-1-iduronidase. The enzymatic defect leads to the accumulation of the glycosaminoglycans (GAGs) in lysosomes causing progressive involvement of many organs and tissues. Over the past fifteen years we have taken care of seven patients suffering from MPS I (five boys and two girls). All of them have been treated symptomatically in order to improve their quality of life and to prolong survival. One patient underwent bone marrow transplantation at the age of two years, but without significant improvement. We have currently under our care two patients with Hurler syndrome that have started therapy with Aldurazyme (recombinant human alpha -L-iduronidase).The first patient, an 8-year-old boy, was diagnosed at the age of 10 months when he was noted to have a thoracolumbar kyphosis. Early signs of MPS such as rhinitis and hernia were also present. The clinical suspicion was confirmed by biochemical investigations which included the quantification of the total GAGs in the urine, their identification, and determination of the alpha-L-iduronidase activity in leukocytes and fibroblasts. At present he has marked symptoms of sleep-apnea syndrome, obstructive lung disease, and the first signs of the cardiac disease. He has developed some of the serious complications of MPS - spinal cord compression at the C7-Th1 level along with syringomielia, and marked visual impairment due to corneal clouding and glaucoma. Despite his severe physical problems his mental condition is still well preserved.The second patient is a 7-year-old girl who presented at the age of 2.5 months with nonspecific neurological signs. The diagnosis of MPS I was established at the age of 3 months. Despite the early diagnosis, no specific treatment was introduced. Frequent upper respiratory infections and middle ear disease dominated during infancy leading to hearing impairment. Her visual acuity is low because of the corneal clouding. She has not developed cardiac complications, but she has marked joint stiffness and refuses to walk. Her intellectual development is at the lower limit of moderate mental retardation. The third case is a boy at age of 2 years and 3 months when MPS I was diagnosed. The most prominent clinical findings were coarse face, macrocephaly, hepatosplenomegaly and bilateral inguinal hernia. He had increased excretion of dermatan-, heparan- and chondroitin-sulphate. Total urinary glucosaminoglycans were 44 mg/mol creatinine (normal > 20). In fibroblasts there was no activity of a-L-iduronidase. Currently, at age of 4 years additional clinical signs are joint contractures, corneal clouding and mitral valve insufficiency. Mental development is normal. In the first two cases enzyme replacement therapy with Aldurazyme has been started. It is too early to evaluate outcome of the therapy but we hope that the enzyme replacement therapy using recombinant human a-L-iduronidase will alleviate at least some of the symptoms, preserving or improving their quality of life.

mucopolysaccharidosis; MPS type I; enzyme replacement therapy

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