1/20. Hurler's syndrome, West's syndrome, and vitamin d-dependent rickets.mucopolysaccharidosis i is a metabolic disease of autosomal recessive inheritance caused by deficient activity of alpha-L-iduronidase. The clinical phenotype presents a wide spectrum of signs in the first year of life. We report a child with clinical features and laboratory data consistent with mucopolysaccharidosis I who precociously developed hydrocephalus and flexion spasms with hypsarrythmia in the electroencephalographic registration characteristic of West's syndrome. His radiologic and biochemical data suggested vitamin d-dependent rickets. To our knowledge, this is the first report of a patient demonstrating an association among mucopolysaccharidosis 1, West's syndrome, and vitamin d-dependent rickets.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
2/20. life-threatening pulmonary hemorrhages post bone marrow transplantation in Hurler syndrome. Report of three cases and review of the literature.Hurler syndrome (MPS-IH) is an autosomal recessive mucopolysaccharide storage disorder caused by deficiency of lysosomal alpha-L-iduronidase (IDU) enzyme activity. This results in accumulation of heparan sulfate and dermatan sulfate substances. Untreated children develop progressive developmental deterioration and multisystem morbidity with a median survival of 5 years. Allogeneic bone marrow transplantation (BMT) is the only long-lasting treatment that ameliorates or halts the aggressive course of the disease. Pulmonary hemorrhage (PH) is an unusual complication of BMT and has not been previously reported in MPS-IH post-BMT. We report three children with MPS-IH with life-threatening PH around the time of engraftment. All needed intensive-care support and one child developed recurrent PH that required prolonged ventilation.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
3/20. Proliferation of abnormal bone marrow histiocytes, an undesired effect of granulocyte macrophage-colony-stimulating factor therapy in a patient with Hurler's syndrome undergoing bone marrow transplantation.Granulocyte macrophage-colony-stimulating factor (GM-CSF) has shown promise as a means of alleviating leukopenia associated with a wide variety of disorders. It is currently undergoing evaluation as an adjunct to bone marrow transplantation but its use in patients with metabolic disorders, such as Hurler's syndrome (HS), has not been explored. We followed bone marrow morphology in a 2-year-old male with HS who received up to 8 micrograms/kg GM-CSF per day because of failure of allogeneic bone marrow engraftment. Both premortem and postmortem bone marrow sampling revealed almost complete replacement of the marrow space by sheets of histiocytes demonstrating metachromatic cytoplasmic granules. Such cells were present in far greater numbers than are usually seen in untreated patients with HS or patients with HS undergoing successful bone marrow transplantation without GM-CSF. Moreover, the in vitro culture of bone marrow from a second HS patient showed a GM-CSF dose-related increase in colony formation up to a dose of 250 units/ml. Microscopic examination of these colonies showed a high percentage of histiocytes identical to those seen in the patient's bone marrow. These observations suggest that caution should be exercised when considering administration of CSFs to patients with HS and similar metabolic storage diseases.- - - - - - - - - - ranking = 4keywords = life (Clic here for more details about this article) |
4/20. Treatment of Epstein-Barr virus lymphoproliferative disease after hematopoietic stem-cell transplantation with hydroxyurea and cytotoxic T-cell lymphocytes.Epstein-Barr virus (EBV) lymphoproliferative disease (LPD) is a potentially fatal complication that may follow allogeneic hematopoietic stem-cell transplantation (HSCT). In this article, the authors report a 2-year-old girl with Hurler's syndrome who developed multiple central nervous system (CNS) EBV LPD lesions 1 year after unrelated donor HSCT. Before this CNS occurrence, the patient had a complete response to rituximab treatment for EBV LPD of the spleen and lymph nodes; however, treatment of the CNS disease with rituximab proved ineffective. Because of reported favorable response of primary CNS EBV LPD in two human immunodeficiency virus-positive patients, the authors treated this patient with low-dose oral hydroxyurea. The patient improved clinically, with a decrease in size of multiple EBV LPD brain lesions. Subsequently, the patient received EBV-specific cytotoxic T-cell lymphocytes and remains well. The benefit and limited toxicity of hydroxyurea therapy merit its further consideration as treatment for EBV LPD.- - - - - - - - - - ranking = 5keywords = life (Clic here for more details about this article) |
5/20. Hurler syndrome: a patient with abnormally high levels of alpha-L-iduronidase protein.Mucopolysaccharidosis type I (MPS I: McKusick 25280) is a clinically heterogenous lysosomal storage disorder which is caused by a variable deficiency in alpha-L-iduronidase activity (alpha-L-iduronide iduronohydrolase, EC 3.2.1.76). Cultured fibroblasts from an MPS I patient (cell line 2827) with a severe clinical phenotype (Hurler syndrome) have been characterized using immunochemical and biochemical techniques. Using a specific immunoquantification assay, we have demonstrated that cell line 2827 had an alpha-L-iduronidase protein content (189 ng/mg of extracted cell protein) at least six times greater than the mean level found in normal control fibroblasts (30 ng/mg of extracted cell protein). This was the only MPS I cell line, from a group of 23 MPS I patients, that contained greater than 7% of the mean level of alpha-L-iduronidase protein detected in normal controls. cell line 2827 had very low alpha-L-iduronidase activity toward the fluorogenic substrate 4-methylumbelliferyl-alpha-L-iduronide, and a radiolabeled disaccharide substrate derived from heparin. Maturation studies of alpha-L-iduronidase in cell line 2827 showed apparently normal levels of alpha-L-iduronidase synthesis with delayed processing to the mature form. Subcellular fractionation experiments demonstrated alpha-L-iduronidase protein in lysosomal-enriched fractions isolated from cell line 2827, suggesting a normal cell distribution and supporting the proposed delayed processing. It is proposed that the MPS I patient described has an alpha-L-iduronidase gene mutation which affects both the active site and post-translational processing of the enzyme. This mutation must be structurally conservative because it does not result in instability either during maturation or in the lysosome.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
6/20. Gross and fine motor skills of children with Hurler syndrome (MPS-IH) post umbilical cord blood transplantation: a case series report.PURPOSE: Recent advancements in medical treatment of Hurler syndrome have resulted in longer life expectancies and a greater need for therapeutic services. The purpose of this case series is to provide recommendations for assessing children with Hurler syndrome after umbilical cord blood transplant (UCBT). CLINICAL DESCRIPTIONS: Two children with Hurler syndrome were seen for longitudinal assessments following an UCBT for Hurler syndrome. methods: The raw scores and percentage of fine and gross motor items each child completed on the Motor Scale of the Bayley Scales of infant Development II (BSID-II) were reviewed. RESULTS: Both children gained new motor skills with each successive motor assessment. Both children were able to complete a higher percentage of fine motor skills than gross motor skills in the most advanced item set assessed. DISCUSSION: The children presented in these two case reports both had better fine motor skills than gross motor skills, which inflated their standard scores on the BSID-II. Clinicians assessing children with Hurler syndrome should use standardized assessments that allow for differentiation of fine and gross motor skills to prevent this situation.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
7/20. Hurler's syndrome: dental findings in a case treated with bone marrow transplantation in infancy.Hurler's syndrome, also known as mucopolysaccharidosis i (MPS I-H), is a rare condition inherited as an autosomal recessive trait. It is caused by a deficiency in alpha-L-iduronidase, an enzyme that participates in the degradation of the glycosaminoglycans (GAGs) heparin sulphate and dermatan sulphate. Children with Hurler's syndrome appear nearly normal at birth but, left untreated, show a progressive mental and physical deterioration caused by a build-up of GAGs in all organs of the body. death is often caused by cardiac or respiratory failure and usually occurs before the second decade of life. In recent years, bone marrow transplantation (BMT) has been employed in the management of patients with Hurler's syndrome. However, the dental findings observed in these cases have not previously been reported in the dental literature. Here we report a patient aged 11 years and 6 months, presented to a Specialist Paediatric dentistry Unit, who was successfully treated by BMT at 18 months of age.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
8/20. Hurler syndrome with special reference to histologic abnormalities of the growth plate.Hurler syndrome is a mucopolysaccharide disorder resulting from an heritable deficiency in alpha-L-iduronidase, an enzyme required in the catabolism of heparan sulfate and dermatan sulfate glycosaminoglycan (GAGs). The resultant intracellular accumulation of GAG leads to disruption of the intracellular and extracellular environment and dysfunction of multiple organ systems. Among the most noted manifestations of this disease is disproportionate short trunk dwarfism, which develops during the first years of life. Histochemical and electron-microscopic observations on a 30-month-old child with Hurler syndrome showed marked irregularities in chondrocyte orientation within the growth plate, along with disruption of the normal columnar architecture. Vacuolization with enlargement of the cellular border was the characteristic ultrastructural finding. An heritable abnormality in the enzymatic degradation of structural glycosaminoglycans leads to profound disruption of the normal mechanisms of growth and development.- - - - - - - - - - ranking = 1keywords = life (Clic here for more details about this article) |
9/20. The management of otolaryngological problems in the mucopolysaccharidoses: a retrospective review.The mucopolysaccharidoses are rare, genetically transmitted metabolic disorders that affect children early in life. These potentially life-threatening diseases almost invariably involve the auditory apparatus and the upper respiratory tract. Thus, the otolaryngologist is frequently involved in the care of these patients. This paper presents a 10-year retrospective review of the management of these patients at the Hospital for Sick Children. Data concerning auditory and upper respiratory pathology are presented. Results indicate that persistent serous otitis, sensorineural hearing loss, and upper respiratory obstruction leading to sleep apnea, are frequent findings in these patients. Specific recommendations are made with regard to appropriate otolaryngologic intervention in children affected with these diseases.- - - - - - - - - - ranking = 2keywords = life (Clic here for more details about this article) |
10/20. A case of mucopolysaccharidoses type I with heart involvement during infancy.We report a case of mucopolysaccharidoses I with severe cardiac involvement, which was diagnosed on the basis of clinical and laboratory findings even though, symptoms begin to occur in mucopolysaccharidoses after the first year of life. In our case cardiac failure occurred in the third month of life, which resulted in the patient's death after one month.- - - - - - - - - - ranking = 2keywords = life (Clic here for more details about this article) |
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