ABC | Volume 113, Nº1, July 2019

Original Article Chaves-Markman et al A novel mutation in Fabry disease Arq Bras Cardiol. 2019; 113(1):77-84 Figure 1 – Chromatogram of the novel GLA gene mutation: c.967C>A (p.Pro323Thr). FD has X-linked inheritance. The classic X-linked disorder generally shows a vertical transmission, in which heterozygous females transmit the allele down to their offspring . The majority of mutations in X-linked genes result in diseases that will only occur in males. However, some of the X-linked diseases show different rates of penetrance and expressivity in both genders. In FD, heterozygous individuals (females) are usually affected, but tend to have a milder and more variable phenotype than homozygous ones (males). 20 The prevalence of FD is estimated to be 0.02–0.09:10,000 in the overall population, though molecular screening in newborns suggests a higher prevalence. 21,22 Regarding the cardiac variant, the prevalence may be as high as 12%, depending on the method used. 23–26 The mean maximum ventricular thickness (MVT) in patients with GLA mutation in our sample was greater than that in previous studies. The mean MVT was 11.6 ± 3.3 mm in the study by Koskenvuo et al., 27 and only eight patients Table 2 – Clinical characteristics and complementary test results of FD patients Patient 1 Patient 2 Patient 3 Patient 4 Age (years) 69 39 72 53­ Gender F F F M Cardiac symptoms Syncope Syncope, dyspnea No No Extracardiac symptoms TIA Acroparesthesia , intolerance to heat/cold, mood changes Acroparesthesia, arteria thrombosis ICVA ECG RHR, LVO, FDAVB, LBBB RHR, LVO RHR, LVO, FDAVB RHR, LVO 24h Holter 8 episodes of VT, 677 PVC No arrhythmias Paroxysmal AFib No arrhythmias EF † 67% 60% 70% 65% Predominance of LVH † Apical Asymmetrical septal hypertrophy Asymmetrical septal hypertrophy Concentric MVT (mm) † 19 20 18 18 Diastolic disfunction † Mild Pseudonormal Mild Mild LVOTO † No No No No Fibrosis on MRI 6% 28% 13% 1.36% FSD Yes Yes No No ICD Yes Yes No No GLA gene mutation c.967C>A (p. Pro323Thr) c.937G>T (p.Asp313Tyr) c.352C>T (p.Arg118Cys) c.352C>T (p.Arg118Cys) High lyso-Gb3 No No No No Low α-Gal A NM NM NM Yes Proteinuria No No Yes No F: female; M: male; TIA: transitory ischemic attack; ICVA: ischemic cerebrovascular accident; ECG: electrocardiogram; RHR: regular heart rate; LVO: left ventricular overload; FDAVB: first degree atrio-ventricular block; LBBB: left bundle branch block; VT: ventricular tachycardia, PVC: premature ventricular contraction; AFib: atrial fibrillation; EF: ejection fraction; LVH: left ventricular hypertrophy; MVT: maximum ventricular thickness; LVOTO: left ventricular outflow tract obstruction; MRI: magnetic resonance imaging; FSD: family sudden death; ICD: implantable cardioverter defibrillator; NM: not measured. † measurement via transthoracic echocardiography (TTE). 80