TY - JOUR
T1 - Chronic kidney disease and an uncertain diagnosis of Fabry disease: Approach to a correct diagnosis
AU - van der Tol, Linda
AU - Svarstad, Einar
AU - Ortiz, Alberto
AU - Tøndel, Camilla
AU - Oliveira, João Paulo
AU - Vogt, Liffert
AU - Waldek, Stephen
AU - Hughes, Derralynn A.
AU - Lachmann, Robin H.
AU - Terryn, Wim
AU - Hollak, Carla E.
AU - Florquin, Sandrine
AU - van den Bergh Weerman, Marius A.
AU - Wanner, Christoph
AU - West, Michael L.
AU - Biegstraaten, Marieke
AU - Linthorst, Gabor E.
PY - 2015
Y1 - 2015
N2 - Background and objectives: Screening for Fabry disease (FD), an X-linked lysosomal storage disorder, reveals a significant number of individuals with a genetic variant of unknown significance without classical FD manifestations; these variants in the a-galactosidase A gene often result in a high residual leukocyte alpha-galactosidase A and it is unclear whether these individuals suffer from FD. Therefore, a structured diagnostic approach is warranted. We present a diagnostic algorithm on how to approach adults with chronic kidney disease and an uncertain diagnosis of FD nephropathy. Design, setting, participants, and measurements: A modified Delphi procedure was conducted to reach consensus among 11 FD experts. A systematic review was performed to identify possible criteria that could confirm or exclude FD nephropathy. Results: The gold standard for FD nephropathy was defined as characteristic storage on electron microscopy (EM) in a kidney biopsy in the absence of medication that may induce similar storage. The suggested criteria to confirm FD nephropathy are as follows: 'renal cysts', 'Maltese cross sign', immunohistochemical staining of Gb3 in urine' and 'high urinary Gb3'; and to exclude FD nephropathy: 'absence of renal cysts', 'small kidneys' and 'high protein excretion' were rejected because of low or uncertain specificity. Urinary Gb3 may be increased in other kidney diseases and there was no agreement on this criterion, although a third of the panel indicated that it is sufficient to diagnose FD nephropathy. The 'Maltese cross sign' and 'high urinary Gb3' were selected as red flags to suggest the possibility of FD nephropathy, but are not sufficient for a definite diagnosis of FD nephropathy. Conclusions: In adults with chronic kidney disease, an a-galactosidase A gene variant and an uncertain diagnosis of FD, a kidney biopsy with EM analysis should be performed to confirm or reject the diagnosis of FD nephropathy. Other criteria currently cannot substitute for a biopsy in these cases. (C) 2014 Elsevier Inc All rights reserved
AB - Background and objectives: Screening for Fabry disease (FD), an X-linked lysosomal storage disorder, reveals a significant number of individuals with a genetic variant of unknown significance without classical FD manifestations; these variants in the a-galactosidase A gene often result in a high residual leukocyte alpha-galactosidase A and it is unclear whether these individuals suffer from FD. Therefore, a structured diagnostic approach is warranted. We present a diagnostic algorithm on how to approach adults with chronic kidney disease and an uncertain diagnosis of FD nephropathy. Design, setting, participants, and measurements: A modified Delphi procedure was conducted to reach consensus among 11 FD experts. A systematic review was performed to identify possible criteria that could confirm or exclude FD nephropathy. Results: The gold standard for FD nephropathy was defined as characteristic storage on electron microscopy (EM) in a kidney biopsy in the absence of medication that may induce similar storage. The suggested criteria to confirm FD nephropathy are as follows: 'renal cysts', 'Maltese cross sign', immunohistochemical staining of Gb3 in urine' and 'high urinary Gb3'; and to exclude FD nephropathy: 'absence of renal cysts', 'small kidneys' and 'high protein excretion' were rejected because of low or uncertain specificity. Urinary Gb3 may be increased in other kidney diseases and there was no agreement on this criterion, although a third of the panel indicated that it is sufficient to diagnose FD nephropathy. The 'Maltese cross sign' and 'high urinary Gb3' were selected as red flags to suggest the possibility of FD nephropathy, but are not sufficient for a definite diagnosis of FD nephropathy. Conclusions: In adults with chronic kidney disease, an a-galactosidase A gene variant and an uncertain diagnosis of FD, a kidney biopsy with EM analysis should be performed to confirm or reject the diagnosis of FD nephropathy. Other criteria currently cannot substitute for a biopsy in these cases. (C) 2014 Elsevier Inc All rights reserved
U2 - https://doi.org/10.1016/j.ymgme.2014.08.007
DO - https://doi.org/10.1016/j.ymgme.2014.08.007
M3 - Article
C2 - 25187469
SN - 1096-7192
VL - 114
SP - 242
EP - 247
JO - Molecular Genetics and Metabolism
JF - Molecular Genetics and Metabolism
IS - 2
ER -