A case of Anderson-Fabry disease: a multidisciplinary approach for diagnosis and follow up

Abstract

Fabry disease (also known as Anderson-Fabry disease, angiocheratoma corporis diffusum, diffuse angiocheratoma) is a rare tesaurismosis linked to the deficiency of the lysosomal enzyme alpha-galactosidase A, required for the physiological catabolism of glycosphingolipids.

The related clinical signs show a multisystemic feature and define a degenerative and disabling pathology, whose approach requires a close multidisciplinary specialist collaboration.

Currently, the renewed interest in the disease is aimed at the need to provide an early diagnosis, in order to early begin the enzyme replacement therapy and to slow down or avoid the establishment of irreparable organ damage. For this reason, the diagnostic suspicion becomes crucial and arises from the careful observation and research of the symptoms, together with the anamnesis and the overall clinical evaluation of the patient.

Keywords: Fabry disease, alpha-galactosidase, sphingolipids, enzymatic replacement therapy

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CASO CLINICO

Riportiamo il caso di un paziente di 47 anni, portatore di fattori di rischio per vasculopatia (BMI >35, dislipidemia, fumo, ipertensione arteriosa) e in follow up per insufficienza renale cronica stadio IIIa secondo NKF/KDOQI (sCr 1,3 mg/dL con eGFR 65 mL/min/1,73 mq sec. MDRD), ACR grado A2 (150 mg/g) confermate in più determinazioni successive nell’arco di sei mesi. L’ecografia renale non rivelava alterazioni degne di nota. In precedenza, non era stato possibile effettuare una diagnosi istologica avendo il paziente rifiutato di sottoporsi a biopsia renale.

 

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Screening Test of Fabry Disease in Patients with Renal Replacement Therapy in the City of Modena

Abstract

Fabry disease is a rare genetic lysosomal storage disease, inherited in an X-linked manner, characterized by lysosomal deposition of globotriaosylceramide due to deficient activity of the enzyme α-galactosidase A. Because the prevalence of this genetic disorder is unknown in the Emilia Romagna region, we conducted a screening study to assess the prevalence of Fabry disease in the city of Modena, Italy.

Material and Methods

A screening study has been conducted in patients on renal replacement therapy at University Hospital of Modena. Screening tests have been performed using dried blood spot method. Alpha-galactosidase A activity and Lyso-Gb3 levels were evaluated in peripheral blood of all men. In women test based on genetic analysis; Lyso-Gb3 was measured only in patients with mutation of gene GLA.

Results

Screening tests have been performed on 388 subjects: 181 maintenance hemodialysis patients, 166 kidney transplant recipients and 41 peritoneal dialysis patients. About 40% of the patients did not had etiological diagnosis of renal disease. Lyso-Gb3 was more specific test than α- galactosidase A (100% vs. 82.5%) to diagnose Fabry disease. We found two different mutations: c.13 A>G p.(Asn5Asp), a variant likely benign and c.937 G>T p.(Asp313Tyr) a variant of uncertain significance. Both the patients carrying these genetic mutations had no symptoms or medical history compatible with Fabry disease.

Conclusion

Identification of variant of uncertain significance such as c.937G>Tp.(Asp313Tyr) showed the limits of genetic analysis to diagnose an inherit disease. Further studies are need to assess the diagnostic value of Lyso-Gb3 for screening for Fabry disease.

KEYWORDS: Fabry Disease, Screening; Lyso-Gb3; c.13 A>G p. Asn5Asp; c.937 G>T p.(Asp313Tyr); D313Y; α-galactosidase A

Sorry, this entry is only available in Italian. For the sake of viewer convenience, the content is shown below in the alternative language. You may click the link to switch the active language.

Introduzione

La Malattia di Anderson Fabry è una malattia genetica legata al cromosoma X dovuta al deficit enzimatico dell’α-galattosidasi A per mutazioni del gene GLA (1). L’α-galattosidasi A è un enzima lisosomiale responsabile del metabolismo degli glicosfingolipidi. La sua carenza determina l’accumulo di globotriaosilceramidi (GL-3, Gb 3, CTH) nei lisosomi e di globotriaosilsfingosine (Lyso-GL-3, Lyso-Gb3) nel circolo ematico (2). 

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