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Fabry disease due to D313Y and novel GLA mutations
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  • Published on:
    Fabry disease requires a multidisciplinary approach
    • Konstantinos Koulousios, Nephrologist MD University of Thessaly, School of Medicine
    • Other Contributors:
      • Anastasios E. Germenis, Professor and Chairman

    We are delighted to read the misleadingly entitled letter by Karapanagiotidis and Grigoriadis, as it gives us the opportunity to present additional convincing evidence gathered after publication in favor of the pathogenicity of the D313Y GLA mutation. It might also be noted that Karapanagiotidis and Grigoriadis refer to only two of the reported cases, disregarding the strong supporting evidence provided by the study of the other cases. Obviously, their objections come from the fact that they were restricted to the neurological approach to Patient 4 (thus their mention in the Acknowledgements of our paper), underestimating her nephrological profile, which is not even mentioned in their letter. Taking into account that, one year after the last stroke, the patient presented with microalbuminuria that was duplicated after 3 months, as was mentioned in our paper, we proceeded to renal biopsy. On electron microscopy, typical signs of Fabry disease were detected, i.e. podocyte injury, significant cytoplasmic vacuolization of podocytes with a mild presence of sphingolipids and myelin bodies in podocytes and tubular cells. According to the current diagnostic criteria, these findings confirm the definite diagnosis of Fabry disease in patients with “genetic variants of uncertain significance and non-specific FD signs” (Biegstraaten et al, Orphanet J Rare Dis 2015). Additionally, in a recent ophthalmological assessment, this patient presented with signs of "cornea verticillata...

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    Conflict of Interest:
    None declared.
  • Published on:
    D313Y variant: Evidence in favour or against its pathogenicity in Fabry Disease?
    • Theodoros Karapanayiotides, Assistant Professor of Neurology Aristotle University of Thessaloniki, 2nd Department of Neurology, AHEPA University Hospital, Thessaloniki, Greece
    • Other Contributors:
      • Nikolaos Grigoriadis, Professor of Neurology

    Dear Editor,

    We read with interest the article by Koulousios et al. The authors report five patients with a presumed “definite” diagnosis of Fabry Disease (FD) out of a group of 17 Greek individuals with the D313Y variant of the a-galactosidase A (GLA) gene. The authors claim that they provide “strong evidence that the D313Y mutation could be pathogenic”. Beyond the obvious contradiction of being certain about an uncertainty, the study contradicts to overwhelming evidence from the literature, mainly due to a mechanistic interpretation of incomplete patient data without (in the majority of cases) the appropriate counseling and expertise by the medical specialties responsible for the management of the patients’ principal clinical manifestations. In particular, the authors claim that the “vast majority of patients with the D313Y mutation presented with neurologic symptoms and signs”. Nevertheless, none of the authors is a neurologist and it is obvious that a neurological perspective is missing from the manuscript.
    For the past two years, we have been following in our department Patient 4 (table 1) and her mother (Patient 5). Patient 5 had a history of slowly progressing spastic tetraparesis over at least 20 years, initially diagnosed in another institution as primary progressive multiple sclerosis. After all relevant investigations, our diagnosis was that of an undetermined moderate leukoencephalopathy. Plasma Gb3 levels were 4.7 nmol/mL (reference: 0.8-4.52). I...

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    Conflict of Interest:
    None declared.