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Título

Could R118C be Fabry Disease? Case series analysis

Relato do Caso

Introduction: Fabry Disease (FD) is a monogenic disease related to a variant in the GLA gene leading to a reduction/absence of alpha-GAL activity. R118C is a variant of the GLA gene classified as a variant of unknown significance( VUS) some authors describe it as being a variant that causes involvement of the central nervous system leading to strokes and others describe it as not causing. The aim was to describe a case series of R118C variants (index case and family members) with investigation to conclude about the pathogenesis.
Methods: We investigated an index case of R118C variant in a 40-year-old female patient and the family history evaluation of Fabry symptoms, kidney, heart, and central nervous system involvement.
Results: The index case was identified as having the R118C variant in the GLA gene -NM_000169.2:c.352C>T; p.(Arg118Cys), chronic kidney disease of unknown etiology, and no symptoms of FD . The levels of lyso-GB3 were normal (0.8ng/dl). There was no family history of Stroke. The patient had no kidney biopsy performed. She had a normal brain magnetic resonance, and an echocardiogram with a left ventricular mass index of 139 g/m2; septal of 14.5mm, posterior wall of 13mm, normal ejection fraction, and diastolic dysfunction, magnetic resonance showed normal values of T1, no late gadolinium enhancement, and no fibrosis, concluded by the presence of left ventricular hypertrophy not suggestive of FD. We performed a myocardial biopsy with no signs of vacuolization and immunofluorescence for GB3 was negative. She was submitted to a deceased donor kidney transplant, and after we decided to stop investigation because of the absence of evidence of Fabry. Family histories were found a mother, a sister, a niece, and a nephew with the same variant, with no FD symptoms. The nephew with R118C, 8-years-old, male had alpha-GAL activity of 50%, normal lyso-GB3 and absence of renal and cardiac involvement.
Conclusion: We describe a female patient with R118C variant retrieved by hemodialysis screening that was not associated with Fabry Disease. In the evaluation of family history the patients had no signs of Fabry ( kidney, cardiac, or central nervous system involvement) . We screened a male patient (nephew) with the same variant with normal levels of lyso-GB3, and 50% reduction of alpha-GAL activity. We showed that R118C was not pathogenic in this family.

Palavras Chave

Fabry, Fabry Disease, R118c gene, patogenesis