Effects of enzyme replacement therapy for cardiac-type Fabry patients with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A)

Abstract

ObjectiveCurrent studies of newborn screening for Fabry disease in Taiwan have revealed a remarkably high prevalence of cardiac-type Fabry disease with a Chinese hotspot late-onset Fabry mutation (IVS4+919G>A).DesignRetrospective cohort study.SettingTertiary medical centre.Participants21 patients with cardiac-type Fabry disease (15 men and 6 women) as well as 15 patients with classic Fabry disease (4 men and 11 women) treated with biweekly intravenous infusions of agalsidase β (1 mg/kg) or agalsidase α (0.2 mg/kg) for at least 6 months.Outcome measuresThese data were collected at the time before enzyme replacement therapy (ERT) began and followed up after ERT for at least 6 months, including patient demographics, medical history, parameter changes of cardiac status and renal functions, plasma globotriaosylsphingosine (lyso-Gb3) and Mainz Severity Score Index.ResultsAfter 6–39 months of ERT, plasma lyso-Gb3 was found to be reduced in 89% (17/19) and 93% (14/15) of patients with cardiac-type and classic Fabry disease, respectively, which indicated an improvement of disease severity. For patients with cardiac-type Fabry disease, echocardiography revealed the reduction or stabilisation of left ventricular mass index (LVMI), the thicknesses of intraventricular septum (IVS) and left posterior wall (LPW) in 83% (15/18), 83% (15/18) and 67% (12/18) of patients, respectively, as well as 77% (10/13), 73% (11/15) and 60% (9/15) for those with classic type. Most patients showed stable renal function after ERT. There were statistically significant improvements (p<0.05) between the data at baseline and those after ERT for values of plasma lyso-Gb3, LVMI, IVS, LPW and Mainz Severity Score Index. No severe clinical events were reported during the treatment.ConclusionsERT is beneficial and appears to be safe for Taiwanese patients with cardiac-type Fabry disease, as well as for those with the classic type.

Prevalence and clinical features of Fabry disease in Japanese male patients with diagnosis of hypertrophic cardiomyopathy

“…Although the patient with R112L mutation showed almost zero a-Gal A activity, FD manifestations other than cardiac hypertrophy were not noticeable. The patient with IVS4+919G>A mutation had slight residual a-Gal A activity, and this intronic mutation is known to be a popular mutation causing a cardiac variant form in Taiwan [19]. These two patients showed cardiac hypertrophy after middle age as their clinically initial manifestations and they both showed concentric LVH at the initial diagnosis of HCM, as a generally reported cardiac manifestation.…”

Fibrosis: a key feature of Fabry disease with potential therapeutic implications

“…In Fabry nephropathy the combination of ERT and RAAS targeting to decrease proteinuria prevented progression of CKD in patients with baseline estimated GFR <60 ml/min/1.73 m 2 [7]. An ongoing clinical trial is validating this clinical observation (The Fabrazyme® and Arbs and ACE Inhibitor Treatment (FAACET) Study [94]. However, neither study assessed renal fibrosis.…”

Diagnostic dilemmas in Fabry disease: a case series study on GLA mutations of unknown clinical significance

“…Non‐classical male patients show significant residual AGAL‐A activity, whereas classically affected males have almost completely absent AGAL‐A activity. Recent studies also suggest that non‐classical patients have no or minimally increased plasma globotriaosylsphingosine (lysoGb3), in contrast to the substantial elevation in classical FD patients .…”