Early response to idursulfase treatment in a 3 year-old boy affected of Hunter syndrome
Department of Pediatrics, Hospital Materno-Infantil-Hospital Infanta Cristina, Facultad de Medicina, Avda Damian Tellez Lafuente s/n, 06010 UEX Badajoz, SpainEuropean Journal of Medical Genetics (Impact Factor: 1.47). 05/2008; 51(3):268-71. DOI: 10.1016/j.ejmg.2008.02.005
We present a 3-year-old boy affected with Hunter syndrome. When we first evaluated the patient glycosaminoglycans (GAG) in urine were elevated (94.6 ng/nmol/creatinine); the enzyme activity determined in serum was decreased (3.9 nmol/hxml) and the mutation found was N350H, exon 8. His clinical signs were coarse facial features, hepatomegaly (6 cm), splenomegaly (6 cm), elbow stiffness and hypospadias; dilatation of the perivascular spaces and white matter abnormalities, mitral regurgitation. After two weeks on enzyme replacement therapy (ERT) with idursulfase (IDS), the excretion of GAG was decreased to 36.2 ng/nmol/creatinine and the liver and spleen volumes were reduced to normal limits. He was subsequently noted to have a softer, finer skin, he had no further bouts of bronchitis, and his physical activity improved. This indicates that IDS in young children is well tolerated and that it has several effects which may confer clinical benefits with long-term therapy.
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ABSTRACT: The term ‘angiokeratoma corporis diffusum’ (ACD) has been used synonymously with Anderson-Fabry disease since its original description. Since the availability of effective therapy, the drive to identify patients has increased. As a result, we are becoming more aware of a broader spectrum in the cutaneous and systemic phenotype of the condition. Not all patients have widespread angiokeratomas. Macular (flat) angiomas without any overlying hyperkeratosis and papular- ‘cherry’ angiomas are also seen. Telangiectases may occur at sun exposed sites including the face and ‘V’ of the neck, more rarely they are present in unusual sites, such as flanks and elbow flexures. In addition to these cutaneous vascular lesions, skin signs include characteristic facial features, oedema and lymphoedema of the lower limbs, abnormalities of sweating and Raynaud’s phenomenon. Skin signs are an obvious, outward manifestation of disease and as such are important signs for diagnosis. They represent a significant source of morbidity, have a recognised impact on self-esteem and quality of life, and should be treated appropriately. Of particular interest, is whether the cutaneous phenotype may be helpful not only in making the diagnosis of Fabry disease, but also in assessing or predicting overall disease severity. KeywordsAngiokeratoma-Cherry angioma-Cutaneous vascular lesions-Fabry facial features-Lymphoedema-Hyperhidrosis-Hypohidrosis-Raynaud’s phenomenon
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ABSTRACT: Hunter syndrome (mucopolysaccharidosis type II [MPS II], OMIM309900) is a rare X-linked lysosomal storage disorder caused by deficiency of the enzyme iduronate-2-sulphatase, resulting in accumulation of glycosaminoglycans (GAGs), multisystem organ failure and early death. Enzyme replacement therapy (ERT) with idursulfase is commercially available since 2007. Early access programs were established since 2005. However, limited information on the effects of ERT in young children is available to date. The aim of this analysis was therefore to determine the effects of ERT on patients younger than 5 years of age. We report data from six Spanish patients with confirmed Hunter syndrome who were younger than 5 years at the start of ERT, and had been treated with weekly intravenous infusions of idursulfase between 6 and 14 months. Baseline and treatment data were obtained from the Hunter Outcome Survey (HOS). HOS is an international database of MPS II patients on ERT or candidates to be treated, that collects data in a registry manner. HOS is supported by Shire Human Genetic Therapies, Inc. (Cambridge, MA, USA). At baseline, all patients showed neurological abnormalities, including ventriculomegaly, hydrocephaly, cerebral atrophy, perivascular changes and white matter lesions. Other signs and symptoms included thoracic deformity, otitis media, joint stiffness and hepatosplenomegaly, demonstrating that children under 5 years old can also be severely affected. ERT reduced urinary GAG levels, and reduced spleen (n = 2) and liver size (n = 1) after only 8 months. Height growth was maintained within the normal range during ERT. Joint mobility either stabilized or improved during ERT. In conclusion, this case series confirms the early onset of signs and symptoms of Hunter syndrome and provides the first evidence of ERT beneficial effects in patients less than 5 years of age. Similar efficacy and safety profiles to those seen in older children can be suggested, although further studies including a direct comparison with older patients would still be required.
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ABSTRACT: To use the Hunter Outcome Survey, an international database, to assess the safety and effectiveness of enzyme replacement therapy with idursulfase in patients with Hunter syndrome who started treatment before 6 years of age. The study population included all patients enrolled in the Hunter Outcome Survey who started idursulfase infusions (0.5 mg/kg every other week) before 6 years of age and who had at least one follow-up examination recorded. The study population included 124 patients, younger than 6 years, who had a mean age at start of idursulfase of 3.6 ± 1.6 years (mean ± SD). The mean duration of treatment was 22.9 ± 14.6 months. A total of 69 infusion-related reactions occurred in 33 (26.6%) patients, including three serious infusion-related reactions occurring in a single patient. After at least 6 months of idursulfase, urine glycosaminoglycan levels decreased from 592 ± 188 to 218 ± 115 μg/mg creatinine (P < 0.0001, n = 34). Liver size, estimated by palpation, was also significantly decreased (P = 0.005, n = 23). Similar safety and effectiveness results were seen in patients who were aged 6 years or older when initiating idursulfase. No new safety concerns were identified in patients younger than 6 years, and clinical benefit was suggested by the reduction in liver size.
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