case_images: PMC9822754_01
case_images: Sanger sequencing of exon 6 of the GLA gene. (a) Normal control showing wild-type (WT) sequence. (b) Patient sequence with GLA variant c.809T >C p.(Ile207Thr) in heterozygosity. The arrow indicates the nucleotide position with the sequence variant.
case_images: CRIG2022-3208810.001.jpg
case_images: PMC9822754_03_CRIG2022-3208810.001.jpg
case_images: fig1
case_images: Genetic testing demonstrated the presence of a pathogenic sequence variant in the GLA gene: c.809T >C p.(Ile270Thr), the same as the previous case although not a relative (Figure 1).
case_images: PMC9822754_02
case_images: Pedigrees. The proband is indicated with an arrow. Striped boxes represent males with Fabry disease; striped circles represent females with Fabry disease; slash indicates deceased.
case_images: CRIG2022-3208810.002.jpg
case_images: PMC9822754_03_CRIG2022-3208810.002.jpg
case_images: fig2
case_images: Regarding her family history, although her mother had a hypertrophic cardiomyopathy and her father and brother had ischaemic heart disease and sensorineural hearing loss, genetic testing was negative for FD (Figure 2).
case_images: Medical history and occurrence of events over time in two female patients treated at different stages of FD. aAT1001-011 (NCT00925301), bAT1001-041 (NCT01458119), and cAT1001-042 (NCT02194985). AV, atrioventricular; ECG, echocardiogram; eGFR, estimated glomerular filtration rate, normal: >90 and >60 for omen >50 years15; FD, Fabry disease; GI, gastrointestinal; IBD, irritable bowel syndrome; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; OLE, open-label extension.
case_images: CRIG2022-3208810.003.jpg
case_images: PMC9822754_03_CRIG2022-3208810.003.jpg
case_images: fig3
case_images: At that time, typical FD manifestations (severe sensorineural hypoacusis, cornea verticillata, and angiokeratomas) were also detected (Figure 3). FD. Fabry-specific therapy was immediately initiated with enzyme replacement therapy (ERT) (agalsidase beta) (Figure 3). During follow-up, the patient experienced unexplained syncopes and conduction disturbances (first-degree auriculoventricular blockade with right ventricle bundle branch block and left anterior hemiblock), which were confirmed by a pathological electrophysiological study showing a prolonged Hiss-Ventricular (HV) interval, and the patient was fitted with a permanent dual chamber pacemaker in 2019 (Figure 3).
case_images: Changes in (a) Metabolism. (b) Renal. (c) Cardiac Parameters with treatment at different stages in two cases of FD. alpha-Gal A is expressed as a percentage of normal (% normal). Normal white blood cell activity: 22 nmol free 4 MU released/mg protein/h7 (patient 1); normal laboratory reference activity on dried blood spots samples: 4.7-18.8 mumol/L/h (patient 2); normal Lyso-Gb3: <=0.6 nm/L; normal urine GL-3: <33.8 ng/mL; normal protein excretion rate: <150 mg/24 hours; normal eGFR: >90 mL/min/1.73 m2; normal UACR: <3 mg/mmol; normal LVMI: 43-95 g/m2; normal LVPWT: 6-10 mm; normal IVSD: 6-9 mm. Dotted lines define the end of study (case 1) or treatment switch (case 2). In the cardiac parameters graph of case 1, gaps indicate a different method of measurement. Case 1: urine GL-3 and GL-3 inclusions were measured up to month 12 of the FACETS study; LVMI and LVM not measured at 8, 9, and 10 months; LVPWT measured upto 12 months of the FACETS study; case 2: UACR and LVPWT not measured at years 3 and 4. aNCT00925301, bAT1001-041; cAT1001-042. alpha-Gal A, alpha-galactosidase A; eGFR, estimated glomerular filtration rate; FD, Fabry disease; GL-3, globotriaosylceramide; IVSD, interventricular septal thickness at end diastole; LVMI, left ventricular mass index; LVPWT, left ventricular posterior wall thickness; Lyso-Gb3, globotriaosylsphingosine; OLE, open-label extension; UACR, urine albumin-to-creatinine ratio.
case_images: CRIG2022-3208810.004.jpg
case_images: PMC9822754_03_CRIG2022-3208810.004.jpg
case_images: fig4
case_images: Plasma alpha-Gal A activity was decreased (less than 30%) (Figure 4(a)).
case_images: PMC9822754_03
case_images: Sanger sequencing of exon 6 of the GLA gene. (a) Normal control showing wild-type (WT) sequence. (b) Patient sequence with GLA variant c.809T >C p.(Ile207Thr) in heterozygosity. The arrow indicates the nucleotide position with the sequence variant.
case_images: CRIG2022-3208810.001.jpg
case_images: PMC9822754_03_CRIG2022-3208810.001.jpg
case_images: fig1
case_images: Genetic testing demonstrated the presence of a pathogenic sequence variant in the GLA gene: c.809T >C p.(Ile270Thr), the same as the previous case although not a relative (Figure 1).
case_images: Pedigrees. The proband is indicated with an arrow. Striped boxes represent males with Fabry disease; striped circles represent females with Fabry disease; slash indicates deceased.
case_images: CRIG2022-3208810.002.jpg
case_images: PMC9822754_03_CRIG2022-3208810.002.jpg
case_images: fig2
case_images: Regarding her family history, although her mother had a hypertrophic cardiomyopathy and her father and brother had ischaemic heart disease and sensorineural hearing loss, genetic testing was negative for FD (Figure 2).
case_images: Medical history and occurrence of events over time in two female patients treated at different stages of FD. aAT1001-011 (NCT00925301), bAT1001-041 (NCT01458119), and cAT1001-042 (NCT02194985). AV, atrioventricular; ECG, echocardiogram; eGFR, estimated glomerular filtration rate, normal: >90 and >60 for omen >50 years15; FD, Fabry disease; GI, gastrointestinal; IBD, irritable bowel syndrome; LVEF, left ventricular ejection fraction; LVH, left ventricular hypertrophy; OLE, open-label extension.
case_images: CRIG2022-3208810.003.jpg
case_images: PMC9822754_03_CRIG2022-3208810.003.jpg
case_images: fig3
case_images: At that time, typical FD manifestations (severe sensorineural hypoacusis, cornea verticillata, and angiokeratomas) were also detected (Figure 3). FD. Fabry-specific therapy was immediately initiated with enzyme replacement therapy (ERT) (agalsidase beta) (Figure 3). During follow-up, the patient experienced unexplained syncopes and conduction disturbances (first-degree auriculoventricular blockade with right ventricle bundle branch block and left anterior hemiblock), which were confirmed by a pathological electrophysiological study showing a prolonged Hiss-Ventricular (HV) interval, and the patient was fitted with a permanent dual chamber pacemaker in 2019 (Figure 3).
case_images: Changes in (a) Metabolism. (b) Renal. (c) Cardiac Parameters with treatment at different stages in two cases of FD. alpha-Gal A is expressed as a percentage of normal (% normal). Normal white blood cell activity: 22 nmol free 4 MU released/mg protein/h7 (patient 1); normal laboratory reference activity on dried blood spots samples: 4.7-18.8 mumol/L/h (patient 2); normal Lyso-Gb3: <=0.6 nm/L; normal urine GL-3: <33.8 ng/mL; normal protein excretion rate: <150 mg/24 hours; normal eGFR: >90 mL/min/1.73 m2; normal UACR: <3 mg/mmol; normal LVMI: 43-95 g/m2; normal LVPWT: 6-10 mm; normal IVSD: 6-9 mm. Dotted lines define the end of study (case 1) or treatment switch (case 2). In the cardiac parameters graph of case 1, gaps indicate a different method of measurement. Case 1: urine GL-3 and GL-3 inclusions were measured up to month 12 of the FACETS study; LVMI and LVM not measured at 8, 9, and 10 months; LVPWT measured upto 12 months of the FACETS study; case 2: UACR and LVPWT not measured at years 3 and 4. aNCT00925301, bAT1001-041; cAT1001-042. alpha-Gal A, alpha-galactosidase A; eGFR, estimated glomerular filtration rate; FD, Fabry disease; GL-3, globotriaosylceramide; IVSD, interventricular septal thickness at end diastole; LVMI, left ventricular mass index; LVPWT, left ventricular posterior wall thickness; Lyso-Gb3, globotriaosylsphingosine; OLE, open-label extension; UACR, urine albumin-to-creatinine ratio.
case_images: CRIG2022-3208810.004.jpg
case_images: PMC9822754_03_CRIG2022-3208810.004.jpg
case_images: fig4
case_images: Plasma alpha-Gal A activity was decreased (less than 30%) (Figure 4(a)).