Journal ArticleDOI
The Dutch Fabry cohort: Diversity of clinical manifestations and Gb3 levels
Anouk C. Vedder,Gabor E. Linthorst,M. J. van Breemen,J. E. M. Groener,F. J. Bemelman,A. Strijland,Marcel M.A.M. Mannens,Johannes M. F. G. Aerts,C. E. M. Hollak +8 more
TLDR
Analysis of the characteristics of the Dutch Fabry cohort has revealed that a limited relationship between various disease manifestations exists and that individual symptoms do not correlate with elevated urinary or plasma Gb3 levels, limiting their value as surrogate disease markers.Abstract:
Background: Fabry disease (OMIM 301500) is an X-linked lysosomal storage disorder with characteristic vascular, renal, cardiac and cerebral complications. Globotriaosylceramide (Gb3) accumulates in Fabry patients as a result of α-galactosidase A deficiency. The phenotypic variability is high, but the relationship between clinical symptoms in individual Fabry patients has not been uniformly documented. Also, the relation between the most prominent biochemical abnormalities, elevated Gb3 levels in plasma and urine, and clinical symptoms is not firmly established. Methods: Clinical and biochemical characteristics of 96 (25 deceased) Dutch Fabry patients were collected retrospectively and before the initiation of enzyme therapy. Results: Clinical assessment revealed that median life expectancy was 57 years for male and 72 years for female patients. Cerebral complications, acroparaesthesias and gastrointestinal complications, but not cardiac and auditory complications, were all seen more frequently in male than female patients. Glomerular filtration rate (GFR) was highly variable in male patients, including 2 patients with GFR < 30 ml/min, but median GFR did not differ between males and females (103 and 101 ml/min, respectively). Hyperfiltration was more frequently observed in the female patient group. Microalbuminuria was present in 60% of males and 45% of females. No specific pattern of combined symptoms existed except for a relationship between left ventricular hypertrophy (LVH) and cerebral complications (males 36%, females 32%), or proteinuria (males 35%, females 31%). Gb3 was found to be more elevated in plasma samples from male (n = 26; median 6.27 μmol/L (1.39–9.74)) than female Fabry patients (n = 37; median 2.16 (0.77–4.18)). This was also observed for urinary Gb3: males (n = 22) median 1851 nmol/24 h (40–3724); females (n = 29) median 672 (86–2052). Plasma and urinary Gb3 levels correlated with each other in both males (r = 0.4, p = 0.05) and females (r = 0.4, p = 0.03), but no correlation between elevated Gb3 levels and clinical symptoms could be detected. Conclusion: Analysis of the characteristics of the Dutch Fabry cohort has revealed that a limited relationship between various disease manifestations exists and that individual symptoms do not correlate with elevated urinary or plasma Gb3 levels, limiting their value as surrogate disease markers.read more
Citations
More filters
Journal ArticleDOI
Elevated globotriaosylsphingosine is a hallmark of Fabry disease
Johannes M. F. G. Aerts,Johanna E. M. Groener,Sijmen Kuiper,Wilma E. Donker-Koopman,Anneke Strijland,Roelof Ottenhoff,Cindy P. A. A. van Roomen,Mina Mirzaian,Frits A. Wijburg,Gabor E. Linthorst,Anouk C. Vedder,Saskia M. Rombach,Josanne Cox-Brinkman,Pentti Somerharju,Rolf G. Boot,Carla E. M. Hollak,Roscoe O. Brady,Ben J. H. M. Poorthuis +17 more
TL;DR: It is shown that globotriaosylsphingosine is an inhibitor of α-galactosidase A activity and the increased intima-media thickness in Fabry patients therefore may be related to the presence of this metabolite.
Journal ArticleDOI
Stroke in Fabry disease frequently occurs before diagnosis and in the absence of other clinical events: natural history data from the Fabry Registry
TL;DR: All patients with Fabry disease, regardless of age or gender, should be monitored for possible cerebrovascular complications, as stroke can occur in the absence of other key signs of the disease.
Journal ArticleDOI
Ten-year outcome of enzyme replacement therapy with agalsidase beta in patients with Fabry disease
Dominique P. Germain,Joel Charrow,Robert J. Desnick,Nathalie Guffon,Judy Kempf,Robin H. Lachmann,Roberta Lemay,Gabor E. Linthorst,Seymour Packman,C. Ronald Scott,Stephen Waldek,David G. Warnock,Neal J. Weinreb,William R. Wilcox +13 more
TL;DR: This 10-year study documents the effectiveness of agalsidase beta (1 mg/kg/2 weeks) in patients with Fabry disease, and most patients remained alive and event-free.
Journal ArticleDOI
Life expectancy and cause of death in males and females with Fabry disease: findings from the Fabry Registry.
TL;DR: Most deceased Fabry Registry patients exhibited serious cardiac and renal dysfunction, and late diagnosis may have contributed to the early deaths of these patients.
Journal ArticleDOI
Fabry's Disease
TL;DR: This review covers all basic aspects of Fabry's disease such as epidemiology, pathophysiology, clinical presentation by systems, diagnosis, management, prevention, and repercussions on quality of life.
References
More filters
Journal ArticleDOI
A simple method for the isolation and purification of total lipides from animal tissues.
TL;DR: In this paper, the authors described a simplified version of the method and reported the results of a study of its application to different tissues, including the efficiency of the washing procedure in terms of the removal from tissue lipides of some non-lipide substances of special biochemical interest.
Book
SF-36 health survey: Manual and interpretation guide
TL;DR: TheSF-36 is a generic health status measure which has gained popularity as a measure of outcome in a wide variety of patient groups and social and the contribution of baseline health, sociodemographic and work-related factors to the SF-36 Health Survey: manual and interpretation guide is tested.
Book
The Metabolic and Molecular Bases of Inherited Disease
TL;DR: In this paper, the authors present a list of disorders of MITOCHONDRIAL FUNCTION, including the following: DISORDERS OF MIOCHONDRIC FERTILITY XIX, XVI, XIX.
Journal Article
K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification
Andrew S. Levey,Josef Coresh,Kline Bolton,Bruce Culleton,Kathy Schiro Harvey,T. Alp Ikizler,Cynda Ann Johnson,Annamaria T. Kausz,Paul L. Kimmel,John W. Kusek,Adeera Levin,Kenneth L. Minaker,Robert Nelson,Helmut G. Rennke,Michael Steffes,Beth Witten,Ronald J. Hogg,Susan Furth,Kevin V. Lemley,Ronald J. Portman,George Schwartz,Joseph Lau,Ethan M Balk,Ronald D. Perrone,Tauqeer Karim,Lara Rayan,Inas Al-Massry,Priscilla Chew,Brad C. Astor,Deirdre De Vine,Garabed Eknoyan,Nathan W. Levin,Sally Burrows-Hudson,William F. Keane,Alan S. Kliger,Derrick Latos,Donna Mapes,Edith Oberley,Kerry Willis,George R. Bailie,Gavin J. Becker,Jerrilynn Burrowes,David Churchill,Allan J. Collins,William Couser,Dick DeZeeuw,Alan Garber,Thomas Golper,Frank A. Gotch,Antonio M. Gotto,Joel W. Greer,Richard H. Grimm,Ramon G. Hannah,Jaime Herrera Acosta,Ronald J. Hogg,Lawrence G. Hunsicker,Michael J. Klag,Saulo Klahr,Caya Lewis,Edmund G. Lowrie,Arthur J. Matas,Sally McCulloch,Maureen Michael,Joseph V. Nally,John M. Newmann,Allen R. Nissenson,Keith Norris,William F. Owen,Thakor G. Patel,Glenda Payne,Rosa A. Rivera-Mizzoni,David A. Smith,Robert A. Star,Theodore Steinman,Fernando Valderrábano,John Walls,Jean Pierre Wauters,Nanette Wenger,Josephine P. Briggs +78 more
TL;DR: In the early 1990s, the National Kidney Foundation (K/DOQI) developed a set of clinical practice guidelines to define chronic kidney disease and to classify stages in the progression of kidney disease.
Journal ArticleDOI
Albuminuria and risk of cardiovascular events, death, and heart failure in diabetic and nondiabetic individuals
Hertzel C. Gerstein,Johannes F.E. Mann,Qilong Yi,Bernard Zinman,Sean F. Dinneen,Byron J. Hoogwerf,Jean Pierre Hallé,James B. Young,Andrew Rashkow,Carol Joyce,Shah Nawaz,Salim Yusuf +11 more
TL;DR: The results indicate that any degree of albuminuria is a risk factor for CV events in individuals with or without DM; the risk increases with the ACR, starting well below the microalbuminuria cutoff.
Related Papers (5)
Elevated globotriaosylsphingosine is a hallmark of Fabry disease
Johannes M. F. G. Aerts,Johanna E. M. Groener,Sijmen Kuiper,Wilma E. Donker-Koopman,Anneke Strijland,Roelof Ottenhoff,Cindy P. A. A. van Roomen,Mina Mirzaian,Frits A. Wijburg,Gabor E. Linthorst,Anouk C. Vedder,Saskia M. Rombach,Josanne Cox-Brinkman,Pentti Somerharju,Rolf G. Boot,Carla E. M. Hollak,Roscoe O. Brady,Ben J. H. M. Poorthuis +17 more