Journal of Inherited Metabolic Disease

, Volume 30, Issue 1, pp 68–78 | Cite as

The Dutch Fabry cohort: Diversity of clinical manifestations and Gb3 levels

  • A. C. Vedder
  • G. E. Linthorst
  • M. J. van Breemen
  • J. E. M. Groener
  • F. J. Bemelman
  • A. Strijland
  • M. M. A. M. Mannens
  • J. M. F. G. Aerts
  • C. E. M. Hollak
Original Article

Summary

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.

Abbreviations

αGal A

α-galactosidase A

BPI

Brief Pain Inventory

CVA

cerebrovascular accident

ECG

electrocardiogram

ERPF

effective renal plasma flow

FF

filtration fraction

Gb3

globotriaosylceramide

GFR

glomerular filtration rate

HPLC

high-pressure liquid chromatography

K/DOQI

kidney disease outcomes quality initiative

LVH

left ventricular hypertrophy

LVMass

left ventricular mass

MRI

magnetic resonance imaging

MSSI

Mainz severity score index

PTA

pure-tone average

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Copyright information

© SSIEM and Springer 2007

Authors and Affiliations

  • A. C. Vedder
    • 1
    • 2
  • G. E. Linthorst
    • 1
    • 2
  • M. J. van Breemen
    • 2
  • J. E. M. Groener
    • 2
  • F. J. Bemelman
    • 3
  • A. Strijland
    • 2
  • M. M. A. M. Mannens
    • 4
  • J. M. F. G. Aerts
    • 2
  • C. E. M. Hollak
    • 5
  1. 1.Department of Internal Medicine/Endocrinology and MetabolismAcademic Medical CenterAmsterdamThe Netherlands
  2. 2.Department of Medical BiochemistryAcademic Medical CenterAmsterdamThe Netherlands
  3. 3.Department of Internal Medicine/NephrologyAcademic Medical CenterAmsterdamThe Netherlands
  4. 4.Department of Clinical GeneticsAcademic Medical CenterAmsterdamThe Netherlands
  5. 5.Department of Internal Medicine/Endocrinology and MetabolismAcademic Medical CenterAmsterdamThe Netherlands

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