Table 3.
Demographic, genetic and clinical features observed in Spanish individuals carrying the GLA p.(Arg118Cys) variant.
| Family tree entry |
Gender / age (Y) |
α-Gal activity | GLA gene | CNS | Heart | Kidney | Eye | Other symptoms and comorbidities. | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| (% normal) DBS / plasma |
R118C | 5’UTR | Brain MRI | LVH | IVS (mm) echo / MRI |
Holter monitoring |
sCr / eGFR |
UACR (mg/g) |
||||
| Family 1 | ||||||||||||
| F1:P (II:1) | M / 51 | 38 / ND | + | WT | Normal | Yes | 15 / 14 | SVPB | 0.8 / 103 | 11 | Normal | No. |
| (I:2) | F / 81 | 77 / 83 | + / − | WT | ND | NA | ND / ND | ND | 0.93 / 58 | 2.8 | Cataracts | Primary biliary cirrhosis. |
| (II:3) | F / 48 | 69 / 39 | + / − | WT | Normal | No | 9 / 8 | Normal | 0.8 / 87 | 4 | NA | Hypohidrosis. Goiter. Hypercholesterolemia. |
| (III:4) | F / 15 | 64 / 74 | + / − | WT | ND | NA | ND / ND | ND | 0.7 / 130 | 1.9 | NA | |
| Family 2 | ||||||||||||
| F2:P | F / 50 | 50 / 46 | + / − | WT | ND | Yes | 18 / 15 | SVT | 1.2 / 53 | 486.3 | NA | Angiokeratoma. Hypertension. |
| Family 3 | ||||||||||||
| F3:P (II:1) | F / 55 | 100 / 37 | + / − | WT | Normal | No | 8 / 15.5 | Normal | 0.84 / 78 | 0.3 | NA | Depression. Limb pain. Dyspnea, palpitations; cardiac catheterization at age 53Y, with no evidence of CAD. |
| Family 4 | ||||||||||||
| F4:P (II:5) | F / 82 | 55 / ND | + / − | ND | Cerebral small vessel disease | Yes | 16 / ND | Pacemaker (AV block) | 1.7 / 28 | ND / (uPr = 300 mg/dl) | NA | Orthopnea (NYHA, stage 2). Pulmonary hypertension. Multiple myeloma. |
| (III:1) | F / 67 | 25 / ND | + / + | ND | Parenchymal changes, possibly ischemic | NA | ND / ND | Normal | 1.02 / 57 | 16 | Cataract | Hypertension; osteoporosis; colon cancer. |
| (III:3) | F / 60 | ND / ND | + / + | WT | Frontoparietal subcortical WML | No | 9 / 6 | SVT | 0.8 / 80 | 2.8 | Normal | Hypohidrosis. Weakness. Palpitations. Fibromyalgia. |
| (III:4) | F / 51 | 33 / ND | + / + | WT | Normal | No | 9 / 7 | WAP | 0.6 / 106 | 5.6 | Normal | Paraesthesias. Palpitations. Hyperthyroidism. |
| (IV:1) | M / 36 | 83 / ND | + | WT | Normal | No | 9 / ND | SVPB | 0.9 / 109 | 2.2 | Normal | Angiokeratoma. |
P: proband. Gender: male (M) / female (F). Age in years (Y). α-galactosidase A (α-Gal) enzyme activity, as measured in dried blood spots (DBS) or in plasma, is expressed as percentage (%) of the normal control mean. The molecular data reported for the α-galactosidase A gene (GLA) in each case is the presence of the p.(Arg118Cys)(R118C) variant, either in hemizygosity (+), heterozygosity (+ / −) or homozygosity (+ / +), as well as the presence of any of the 5’-untranslated region (5’UTR) polymorphisms that may affect enzyme expression (−30G>A/−12G>A/10C>T); WT: wild-type 5’UTR sequence.CNS: central nervous system. MRI: magnetic resonance imaging. WML: white matter lesions. LVH: left ventricular hypertrophy, clinical diagnosis. The interventricular septal thickness (IVS) is expressed in mm, as measured by echocardiography (Echo) / cardiac MRI. Holter monitoring (24-hour)— SVPB: supraventricular premature beats; SVT: supraventricular tachycardia; AV: atrioventricular; WAP: wandering atrial pacemaker. sCr: serum creatinine level, expressed as mg/dl; eGFR: glomerular filtration rate estimated by the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation [http://www.kidney.org/professionals/kdoqi/gfr_calculator.cfm], expressed in ml/min/1.73m2. UACR: urine albumin-to-creatinine ratio, expressed as mg of albumin per g of creatinine; uPr: urine protein concentration. Eye: ocular phenotype as described on slit-lamp ophthalmological examination.CAD: coronary artery disease. New York Heart Association (NYHA) functional classification of heart failure. ND: not done/determined; NA: not assessed.