Enzyme Replacement Therapy in Fabry Disease Patients Undergoing Dialysis: Effects on Quality of Life and Organ Involvement

Pisani, Antonio; Spinelli, Letizia; Sabbatini, Massimo; Andreucci, Maria Vittoria; Procaccini, Deni Aldo; Abbaterusso, Cataldo; Pasquali, Sonia; Savoldi, Silvana; Comotti, Cristina; Cianciaruso, Bruno

doi:10.1053/j.ajkd.2005.03.016

Cited by 60 publications

(41 citation statements)

References 25 publications

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“…Moreover, it could contribute to reduce the time elapsing between the onset of the first symptoms and the proper diagnosis of Fabry disease, avoiding useless treatments for the patients and starting the therapy for the disease that to date is available. The data in literature show the importance of specific therapeutic intervention made as early as possible, before the organ involvement becomes irreversible (Pisani et al, 2014(Pisani et al, , 2012(Pisani et al, , 2015(Pisani et al, , 2005Spinelli et al, 2004).…”

Section: Resultsmentioning

confidence: 99%

Molecular and clinical studies in five index cases with novel mutations in the GLA gene

Zizzo

Monte²,

Pisani

et al. 2016

Gene

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Fabry disease is a metabolic and lysosomal storage disorder caused by the functional defect of the α-galactosidase A enzyme; this defect is due to mutations in the GLA gene, that is composed of seven exons and is located on the long arm of the X-chromosome (Xq21-22). The enzymatic deficit is responsible for the accumulation of glycosphingolipids in lysosomes of different cellular types, mainly in those ones of vascular endothelium. It consequently causes a cellular and microvascular dysfunction. In this paper, we described five novel mutations in the GLA gene, related to absent enzymatic activity and typical manifestations of Fabry disease. We identified three mutations (c.846_847delTC, p.E341X and p.C382X) that lead to the introduction of a stop codon in positions 297, 341 and 382. Moreover we found a missense mutation (p.R227P) in the exon 5 of the GLA gene and a single point mutation (c.639+5 GNT) occurring five base pairs beyond the end of the exon 4. These mutations have never been found in our group of healthy control subjects N 2300. The studied patients presented some clinical manifestations, such as cornea verticillata, hypo-anhidrosis, left ventricular hypertrophy, cerebrovascular disorders and renal failure, that, considering the null enzymatic activity, suggest that the new mutations reported here are related to the classic form of Fabry disease. The identification of novel mutations in patients with symptomatology referable to FD increases the molecular knowledge of the GLA gene and it gives clinicians an important support for the proper diagnosis of the disease.

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Section: Resultsmentioning

confidence: 99%

Molecular and clinical studies in five index cases with novel mutations in the GLA gene

Zizzo

Monte²,

Pisani

et al. 2016

Gene

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“…52 Agalsidase beta has been studied in 10 open-labeled, noncontrolled trials with mixed results. Three studies found no effect, [53][54][55] whereas the other seven reported varying degrees of reduction in LVM. 46,47,56 -60 Importantly, the results of these studies suggest that early initiation of therapy leads to a better response.…”

Section: Cardiac Diseasementioning

confidence: 99%

Therapeutic goals in the treatment of Fabry disease

Mehta

West

Pintos-Morell

et al. 2010

Genetics in Medicine

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Purpose: Fabry disease is a progressive multiorgan, multisystem disorder that is caused by a deficiency in the lysosomal enzyme ␣-galactosidase A. Serious renal, cardiac, and cerebrovascular involvement are responsible for much of the morbidity and premature mortality associated with Fabry disease, and neuropathic pain, gastrointestinal problems, and hypohidrosis negatively affect quality of life of patients with Fabry disease. Fabry disease is X-linked, but women are often symptomatic and may be as severely affected as men. Methods: We propose a series of therapeutic and symptomatic goals for use in setting the expectations of enzyme replacement therapy and for assessing the response to enzyme replacement therapy in the treatment of Fabry disease. Results: Enzyme replacement therapy has been available since 2001 and has been associated with benefit in clinical trials, including stabilization of kidney function, improvement of cardiac structure and function, reduction in severity of neuropathic pain, and improvement in gastrointestinal involvement. Conclusions: The presentation of these therapeutic goals will aid in the evaluation of response to enzyme replacement therapy and be useful in establishing an overall management plan for individual patients. Genet Med 2010:12(11):713-720.

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“…During follow-up echocardiography data were available in all six patients and showed an increase in LV mass index of 6% in the 2 years before study entry and of 3% after the 2 years of ERT. Indeed, the mean slope of LV mass index decreased from 0.98 Ϯ 0.01 in the pretreatment period to 0.46 Ϯ 0.96 in the ERT period (P ϭ 0.06) (29).…”

Section: Ert In Dialysis Patientsmentioning

confidence: 99%

“…The clinical outcome of nine patients with Fabry disease after 2 years of treatment with agalsidase beta undergoing dialysis treatment (six hemodialysis, three peritoneal dialysis) was first reported in an open-label, nonrandomized Italian study (29). Six of nine patients enrolled underwent clinical and Doppler echocardiography assessment at baseline and after 24 months by means of physical examination, a questionnaire on typical Fabry manifestations, and two-dimensional echocardiography.…”

Section: Ert In Dialysis Patientsmentioning

confidence: 99%

Dialysis and Transplantation in Fabry Disease

Mignani¹,

Feriozzi²,

Schaefer³

et al. 2010

Clinical Journal of the American Society of Nephrology

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F abry disease results in kidney damage and leads to progressive impairment of renal function in almost all male patients and in a significant proportion of females (1-4). The life expectancy is reduced for both genders (5-7), and the major causes of death include cardiac death, stroke, or the consequences of ESRD (7,8).The availability of enzyme replacement therapy (ERT) since 2001 has led to major expectations with regard to improvement of clinical symptoms and disease burden in patients with Fabry disease (9,10). However, Fabry patients requiring renal replacement therapy (RRT) represent a group of patients with specific comorbidities possibly affecting the outcome and efficacy of ERT (11,12).This article summarizes the current knowledge about the effect of ERT in Fabry patients requiring dialysis therapy or who have received a kidney transplant. A second goal is to address important research questions in the field. What Do We Know? Progression of Fabry NephropathyProteinuria and progressive renal deterioration may develop rapidly in Fabry disease. Schiffmann et al. re-examined the natural history of Fabry nephropathy with a retrospective analysis of 279 men and 168 women. In men with an estimated GFR (eGFR) of more than 60 ml/min/1.73 m 2 , the slope of renal function was Ϫ3 and for women was Ϫ0.9 ml/min/1.73 m 2 per year; for men with eGFR Ͻ60 ml/min/1.73 m 2 , it was Ϫ6.8 and for women it was Ϫ2.1 ml/min/1.73m 2 per year. Patients with proteinuria Ͼ1 g/24 h had a worse prognosis (13). Therefore, clinical experiences addressed to evaluate the role of ERT (14 -17) should be compared with this study and not only with small-scale study results (2). Of interest, women who progress Published online ahead of print. Publication date available at www.cjasn.org.

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Enzyme Replacement Therapy in Fabry Disease Patients Undergoing Dialysis: Effects on Quality of Life and Organ Involvement

Cited by 60 publications

References 25 publications

Molecular and clinical studies in five index cases with novel mutations in the GLA gene

Molecular and clinical studies in five index cases with novel mutations in the GLA gene

Therapeutic goals in the treatment of Fabry disease

Dialysis and Transplantation in Fabry Disease

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