Balkan Journal of Medical Genetics

DIFFICULTIES IN DIAGNOSING FABRY DISEASE IN PATIENTS WITH UNEXPLAINED LEFT VENTRICULAR HYPERTROPHY (LVH): IS THE NOVEL GLA GENE MUTATION A PATHOGENIC MUTATION OR POLYMORPHISM?
Aladağ N, Ali Barman H, Şipal A, Akbulut T, Özdemir M, Ceylaner S
*Corresponding Author: Nesim Aladağ, MD, nesimaladag@hotmail.com, Van Yüzüncü yıl University, Faculty of Medicine, Department of Cardiology, Van, Turkey. Phone: +90 544 961 31 69 / Fax: +90 432 486 54 07
page: 43

RESULTS

The clinical and demographic characteristics and the echocardiographic measurements of 120 patients with idiopathic LVH who underwent genetic examination are shown in Table 1. The majority of the patients were female (n = 58, 69%), and the mean age was 60.3 ± 15.7 years. The mean echocardiographic parameters were as follows: LVEF: 61.4% ± 4.8%, IVS: thickness 15.2 ± 5.4 mm, LVPWD: 13.5 ± 2.1 mm, LVEDD: 50.4 ± 5.2 mm, LVESD: 30.8 ± 8.5 mm, and left atrial diameter: 44.5 ± 6.5 mm. GLA gene mutations were detected in three male patients. One of these mutations (NM_000169.2:IVS6-10G>A [c.1000-10G>A]) was previously associated with FD. Another mutation’s association with FD was considered a benign GLA variant (NM_000169.2:c.937G>T [p.D313Y] [p.Asp313Tyr]). A third was a mutation that had not been previously associated with FD (NM_000169.2:c.941A>T [p.K314M] [p.Lys314Met]). The three mutations mentioned are discussed below with case examples. Case 1. This 56-year-old male patient presented to cardiology with dyspnea on exertion and palpitations. His systemic arterial pressure was 135/82 mmHg, and his heart rate was arrhythmic at 110 beats per minute. His electrocardiogram demonstrated atrial fibrillation and LVH, and his TTE showed concentric LVH, with an EF of 65%. Cerebral white matter lesions were detected on cranial magnetic resonance imaging, and microalbuminuria was detected in a urine analysis. The patient had low α-Gal A activity at 2.80 nmol/ mg/h (normal range: >23.10 nmol/mg/h), and his lyso-Gb3 level was high at 12.80 ng/mL (normal range: <1.30). A genetic analysis revealed the NM_000169.2:IVS6-10G>A (c.1000-10G>A) mutation, which was consistent with the diagnosis of FD (14) (Figure 1). The patient’s family screening showed a similar mutation in seven relatives. For the index patient, ERT was started. Case 2: This 58-year-old male patient, who was experiencing chest pain and shortness of breath, presented to the cardiology department. The patient was suffering from coro- nary artery disease and hypertension and had undergone stunting in the right coronary artery and the left anterior descending coronary artery. A genetic assessment was performed because of unexplained concentric LVH on echocardiography, and the NM_000169.2:c.937G>T (p.D313Y) (p.Asp313Tyr) mutation was found (15) (Figure 2). The patient had normal α-Gal A activity and normal lyso-Gb3 levels. His nephrological, neurological, and ocular assessments were also found to be normal. Case 3. This 58-year-old male patient presented to cardiology with palpitations. He had no known cardiac history. His electrocardiography results showed a normal sinus rhythm and concentric LVH, and his neurological, nephrological, ocular, and other systemic examinations were normal. A genetic analysis revealed the NM_000169.2:c.941A>T (p.K314M) (p.Lys314Met) mutation (14) (Figure 3). The patient had normal α-Gal A activity and normal lyso-Gb3 levels. The same genetic mutation was discovered in two siblings during family screening. However, the patient’s echocardiographic examinations were normal.

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