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Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.

ABSTRACT: Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood-brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) started ERT in 2006, 3 had started it earlier in 2004, enrolled in the phase III trial, and 3 after 2006, as soon as the diagnosis was made. The liver and spleen sizes and urinary GAGs significantly decreased and normalized throughout the treatment. Heart parameters improved, in particular the left ventricular mass index/m(2) decreased significantly. Amelioration of hearing was seen in many patients. Joint range of motion improved in all patients. However, no improvement on respiratory function, eye, skeletal and CNS disease was found. The developmental quotient of patients with a CNS involvement showed a fast decline. These patients were no more testable after 6 years of age and, albeit the benefits drawn from ERT, their quality of life worsened throughout the years. The whole group of patients showed a consistent residual disease burden mainly represented by persistent skeletal disease and frequent need of surgery. This study suggests that early diagnosis and treatment and other different therapies which are able to cross the blood-brain barrier, might in the future improve the MPS II outcome.

SUBMITTER: Parini R

PROVIDER: S-EPMC4750582 | biostudies-literature | 2015 Jun

REPOSITORIES: biostudies-literature

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Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.

Parini Rossella R Rigoldi Miriam M Tedesco Lucia L Boffi Lucia L Brambilla Alessandra A Bertoletti Sara S Boncimino Agata A Del Longo Alessandra A De Lorenzo Paola P Gaini Renato R Gallone Denise D Gasperini Serena S Giussani Carlo C Grimaldi Marco M Grioni Daniele D Meregalli Pamela P Messinesi Grazia G Nichelli Francesca F Romagnoli Marco M Russo Pierluigi P Sganzerla Erik E Valsecchi Grazia G Biondi Andrea A

Molecular genetics and metabolism reports 20150422

Hunter disease is an X-linked lysosomal storage disorder characterized by progressive storage of glycosaminoglycans (GAGs) and multi-organ impairment. The central nervous system (CNS) is involved in at least 50% of cases. Since 2006, the enzymatic replacement therapy (ERT) is available but with no effect on the cognitive impairment, as the present formulation does not cross the blood-brain barrier. Here we report the outcome of 17 Hunter patients treated in a single center. Most of them (11) sta ...[more]

PMID: 26937399

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Project description:BackgroundThe natural history of patients commencing dialysis in East Yorkshire is not well characterised and there is little convincing evidence which has studied the impact of potential factors prior to commencement of renal replacement therapy (RRT) at predicting mortality during dialysis. The aim of this study was to examine the previously published 5-year data on end stage renal disease and co-morbid risk factors for mortality at 10 years.MethodsAn observational cohort study of subjects commencing dialysis in 2001/02 in East Yorkshire with a mean follow up from dialysis initiation of 8.8 years. Predictors of mortality were determined by univariate, multivariate analysis and survival via Kaplan-Meier analysis. Assessment of the utility of the Tangri risk calculator was carried out in addition to slope change in eGFR prior to dialysis commencement.ResultsBaseline characteristics and the preferred mode of dialysis remained concordant with the original trial. The mortality rate at the end of the study period was 60% (56/94) with 30% (29) of patients having been transplanted. Highlighted in the 5 year data a significant proportion of mortality was made up of vascular disease and sepsis (71%) but this proportion had decreased (57%) by 10 years. Cardiac disease was the commonest cause of death but notably in 18% of patients, death was related to dialysis or withdrawal of treatment. Vascular disease and diabetes remained independent risk factors and predicative of mortality. Calcium-phosphate product which was associated in the early years with mortality was not in later years. Use of the risk calculator was predictive of commencement of RRT but not mortality but slope change in eGFR was predictive of mortality.ConclusionsAlthough diabetes and vascular disease remained predictive of mortality, interestingly calcium-phosphate levels are no longer significant and may be a more specific predictor of early cardiac mortality. Slope eGFR changes prior to RRT are a predictor of mortality. We speculate that aggressive management of cardiac risk factors in addition to early transplantation may be key to influencing the impact of survival in this cohort in addition to possible measures to delay renal progression.

Dataset Information

Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.

Publications

Enzymatic replacement therapy for Hunter disease: Up to 9 years experience with 17 patients.

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