scholarly journals Pregnancy Outcome after Exposure to Migalastat for Fabry Disease: A Clinical Report

2019 ◽  
Vol 2019 ◽  
pp. 1-7
Author(s):  
Natalja Haninger-Vacariu ◽  
Sarah El-Hadi ◽  
Udo Pauler ◽  
Marina Foretnik ◽  
Renate Kain ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Pregnancy Outcome ◽  
Fetal Mri ◽  
Hormonal Contraceptives ◽  
Clinical Report ◽  
Wild Type ◽  
Phase 3 ◽  
Recurrent Headache ◽  
Enzyme Replacement ◽  
History Of

Our patient was a 37-year-old woman with Fabry disease (GLA p.R112H) with a medical history of recurrent headache, nausea, vomiting, vertigo, and tobacco use (20 cigarettes/day). Fabry disease was diagnosed in 2005 when she experienced proteinuria, preeclampsia, and hypertension (201/130 mm Hg) during pregnancy (delivered 50 cm, 3.4 kg healthy boy; GLA wild type [WT]). Enzyme replacement therapy was initiated in 2009. The patient enrolled in the phase 3 ATTRACT trial (ClinicalTrials.gov; NCT01218659) and started migalastat in May 2012 while taking hormonal contraceptives. Two years after initiating migalastat, the patient had proteinuria (2166 mg/24 h) without hypertension (131/68 mm Hg), which persisted (788 mg/24 h a month later). Kidney biopsy results were consistent with existing Fabry disease. A serum pregnancy test and ultrasound confirmed pregnancy (18 weeks’ gestation). Migalastat and hormonal contraceptives were stopped; the patient continued to smoke. Fetal MRI was normal at ~29 weeks’ gestation. In October 2014, at 37+ weeks’ gestation, the patient delivered a 45-cm, 2.29-kg healthy girl (GLA WT). Excepting low birth weight, which may be related to the patient’s smoking, pregnancy outcome was normal despite exposure to migalastat for 18 weeks. Migalastat therapy during pregnancy is not advised.

scholarly journals Safety of switching to Migalastat from enzyme replacement therapy in Fabry disease: Experience from the Phase 3 ATTRACT study

2019 ◽  
Vol 179 (6) ◽  
pp. 1069-1073 ◽  
Author(s):  
Derralynn A. Hughes ◽  
Kathleen Nicholls ◽  
Gere Sunder‐Plassmann ◽  
Ana Jovanovic ◽  
Ulla Feldt‐Rasmussen ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Phase 3 ◽  
Enzyme Replacement ◽  
Disease Experience

scholarly journals The Management of Fabry Nephropathy

2016 ◽  
Vol 2 (1) ◽  
pp. pocj.5000203 ◽  
Author(s):  
Renzo Mignani
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Kidney Biopsy ◽  
Supportive Therapy ◽  
Organ Damage ◽  
Enzyme Replacement ◽  
History Of ◽  
Fabry Nephropathy ◽  
Key Questions

A case of an adult female with Fabry disease is described with discussion based on the following key questions: 1. What is the natural history of Fabry nephropathy? 2. What are the indications to perform kidney biopsy in Fabry disease? 3. How to perform the workout of the patient in recognition of systemic organ damage? 4. Is the missed recognition of Fabry disease frequent in dialysis patients? 5. When and which patients are eligible to start enzyme replacement therapy? 6. Is enzyme replacement therapy effective in Fabry nephropathy? 7. What is the outcome of the patient who underwent a kidney transplantation? 8. Is the supportive therapy important in Fabry disease nephropathy? 9. What are the future therapeutic perspectives?

A Case of a 49-Year-Old Man with Nonclassical Fabry Disease Diagnosed by Renal Biopsy

Nephron ◽  
2021 ◽  
pp. 1-4
Author(s):  
Lanjun Fu ◽  
Peipei Zhang ◽  
Qingqing Ye ◽  
Manman Wu ◽  
Lingzhi He
Keyword(s):  
Fabry Disease ◽  
Renal Biopsy ◽  
Correct Diagnosis ◽  
Premature Mortality ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
St Segment ◽  
Major Organ ◽  
History Of ◽  
Gla Gene

Fabry disease (FD) is a rare X-linked lysosomal storage disorder caused by mutations in the galactosidase A (GLA) gene that result in deficiency of α-GLA activity, leading to major organ failure and premature mortality. According to different disease courses, FD can be divided into classical and nonclassical phenotypes. The nonclassical FD phenotype is always absent of characteristic symptoms, which makes identifying it challenging. This article presents a 49-year-old man with a 10-year history of proteinuria and decreased glomerular filtration rate. An electrocardiogram showed a complete right bundle branch block and abnormal Q waves in high lateral, accompanied by dramatically elevated ST segment. Consequently, a renal biopsy was performed. Vacuolation was found in many podocytes in light microscopic examinations. Similarly, a myelin-like structure was detected by electron microscopy. Pathological findings were most consistent with FD. Consequently, genetic analysis, p.R301Q (c.902G>A [p.Arg301Gln]), confirmed the FD diagnosis. Angiotensin receptor blocker and traditional Chinese medicine, but not enzyme replacement therapy, were prescribed due to financial constraints. The patient had stabilization of kidney disease 6 months later. The case showed that renal biopsy should be performed in patients with cardiac and renal symptoms, which could contribute toward the correct diagnosis for nonclassical FD type.

scholarly journals Mulberry bodies in the urine sediment of a patient with chronic kidney disease

2020 ◽  
Vol 1 (3) ◽  
Author(s):  
Carlos Martínez-Figueroa ◽  
Karen Cortés-Sarabia ◽  
Hilda Guadalupe Catalán-Nájera ◽  
Micaela Martínez-Alarcón
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Fabry Disease ◽  
Hereditary Disease ◽  
Urine Sediment ◽  
Enzyme Replacement ◽  
Laboratory Test Results ◽  
Organic Dysfunction ◽  
History Of ◽  
Gla Gene

AbstractObjectivesFabry disease is a hereditary disease caused by a mutation in the α-galactosidase A (GLA) gene resulting in the accumulation of glycosphingolipids in different organs. Timely diagnosis is crucial for the early initiation of treatment to avoid organic dysfunction secondary to lipid accumulation. In view of the above, a number of studies have been performed to assess the role of mulberry bodies as a new diagnostic tool. In this study, we report a case demonstrating the utility of this test.Case presentationWe report the case of a woman of advanced age without a history of chronic disease with symptoms consistent with urinary tract infection (dysuria, pelvic pain, and frequent urination). Based on laboratory test results, a diagnosis of anemia with concomitant chronic kidney disease was established. Urine test revealed microhematuria, proteinuria, urine sediment, and the presence of lipid particles consistent with mulberry bodies.ConclusionsThe identification of mulberry bodies and cells in urine sediment is an easy-to-use tool potentially useful in diagnosing Fabry disease, which may contribute to initiate enzyme replacement therapy in a timely manner and reduce systemic deterioration.

Long-term efficacy and safety of migalastat compared to enzyme replacement therapy in Fabry disease: Phase 3 study results

2015 ◽  
Vol 114 (2) ◽  
pp. S57 ◽  
Author(s):  
Derralynn Hughes ◽  
Daniel G. Bichet ◽  
Roberto Giugliani ◽  
Raphael Schiffmann ◽  
William R. Wilcox ◽  
...  
Keyword(s):  
Enzyme Replacement Therapy ◽  
Fabry Disease ◽  
Replacement Therapy ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Enzyme Replacement ◽  
Term Efficacy ◽  
Study Results

scholarly journals Fabry Disease and Early Stroke

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
U. Feldt-Rasmussen
Keyword(s):  
Fabry Disease ◽  
White Matter Lesions ◽  
Vascular Endothelial ◽  
Lysosomal Storage ◽  
Mortality And Morbidity ◽  
Young Stroke ◽  
Enzyme Replacement ◽  
Hard Data ◽  
History Of ◽  
Corneal Opacities

Fabry disease, an X-linked lysosomal storage disorder, results from deficient activity of the enzyme α-galactosidase A. Affected males with the classic phoenotype have acroparaesthesias, hypohidrosis, and corneal opacities in childhood and develop renal failure, cardiac hypertrophy or strokes in the third to fifth decade of life. Some female heterozygotes are asymptomatic, some as severely affected as males. The natural history of Fabry patients includes transitory cerebral ischaemia and strokes, even in very young persons of both genders. The mechanism is partly due to vascular endothelial accumulation of GL-3. White matter lesions on MRI occur. Both males and females can be safely treated with enzyme replacement; and thus screening for Fabry disease of young stroke populations should be considered. There are, however, no hard data of treatment effect on mortality and morbidity. The analyses of results from ongoing studirs will add to the decision on whether or not to screen young stroke patients for Fabry disease. Finally, stroke prophylactic therapy should be used liberally in patients of both genders with verified Fabry disease. This includes primary prevention such as lifestyle counseling, targeting blood pressure, managing atrial fibrillation, diabetes mellitus, hyperlipidaemia, and ASA.

scholarly journals Human α-Galactosidase A Mutants: Priceless Tools to Develop Novel Therapies for Fabry Disease

2021 ◽  
Vol 22 (12) ◽  
pp. 6518
Author(s):  
Andrea Modrego ◽  
Marilla Amaranto ◽  
Agustina Godino ◽  
Rosa Mendoza ◽  
José Luis Barra ◽  
...  
Keyword(s):  
Enzymatic Activity ◽  
Fabry Disease ◽  
Clinical Manifestations ◽  
Substrate Reduction Therapy ◽  
Cell Transplant ◽  
Lysosomal Storage ◽  
Wild Type ◽  
Enzyme Replacement ◽  
Wide Range

Fabry disease (FD) is a lysosomal storage disease caused by mutations in the gene for the α-galactosidase A (GLA) enzyme. The absence of the enzyme or its activity results in the accumulation of glycosphingolipids, mainly globotriaosylceramide (Gb3), in different tissues, leading to a wide range of clinical manifestations. More than 1000 natural variants have been described in the GLA gene, most of them affecting proper protein folding and enzymatic activity. Currently, FD is treated by enzyme replacement therapy (ERT) or pharmacological chaperone therapy (PCT). However, as both approaches show specific drawbacks, new strategies (such as new forms of ERT, organ/cell transplant, substrate reduction therapy, or gene therapy) are under extensive study. In this review, we summarize GLA mutants described so far and discuss their putative application for the development of novel drugs for the treatment of FD. Unfavorable mutants with lower activities and stabilities than wild-type enzymes could serve as tools for the development of new pharmacological chaperones. On the other hand, GLA mutants showing improved enzymatic activity have been identified and produced in vitro. Such mutants could overcome several complications associated with current ERT, as lower-dose infusions of these mutants could achieve a therapeutic effect equivalent to that of the wild-type enzyme.

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