UNASSIGNED: Fabry disease is a rare X-linked lysosomal storage disorder caused by α-galactosidase A (α-Gal A) deficiency. Reduced or absent enzyme activity causes progressive lysosomal accumulation of globotriaosylceramide (Lyso-Gb3) in various cells throughout the body to trigger inflammation and fibrosis.
UNASSIGNED: We present the first familial case of Fabry Disease in North Macedonia identified based on clinical manifestations and confirmed through enzyme, biomarker, and genetic tests. The index case in the family was a 45-year-old male undergoing hemodialysis therapy. He has had chronic burning uncontrolled limb pain since childhood, intermittent abdominal cramps, anhidrosis, and hypertension. The constellation of clinical presentations accompanied by similar symptoms in close family members prompted the enzyme, biomarker, and genetic analyses for Fabry disease. Genetic testing identified a known pathogenic GLA missense variant c.443G>A or p.(Ser148Asn) in the hemizygous state. Subsequent family studies allowed identification of another hemizygous male and five heterozygous female carriers affected by this X-linked disorder.
UNASSIGNED: We report identification of the first familial case of Fabry disease in North Macedonia and describe the phenotype associated with the Ser148Asn GLA variant. Greater awareness of this rare disease linked to continuous medical education is crucial for timely diagnosis and treatment.

患者男性，60岁。1991年以水肿、蛋白尿起病，随着病程进展逐渐出现心律失常、胃肠道症状、心肌肥厚、心脏瓣膜病变、听力减退等多个脏器受累表现，经历了心脏起搏器植入术、肾移植术、两次心脏瓣膜手术等多次重大手术，至2021年才确诊为法布雷病。基因检测显示GLA基因C.679C>T（p.R227X）突变，并于2022年1月6日启动酶替代治疗，每两周注射阿加糖酶β 1 mg/kg至今。患者治疗后血肌酐141 μmol/L，估算肾小球滤过率47 ml·min-1·1.73 m-2，肌钙蛋白I 204.9 pg/ml，脱乙酰基三己糖酰基鞘脂醇33.82 ng/ml，左心室射血分数59%，室间隔厚度25 mm。健康状况调查问卷简表（SF-36）中生活质量指数评分在生理机能、生理职能、一般健康状况、精力等多个维度均较治疗前改善。通过对患者临床特征、诊断和治疗、基因特点进行总结、分析，旨在提高临床医生对法布雷病的关注和认知水平，推动早期诊断和治疗，积极改善患者预后。.

Fabry disease (FD) is an X-linked disorder resulting in a deficiency of α-galactosidase A (GLA) activity. The R112H mutation of GLA is relatively common in Japanese FD patients, characterized by a late-onset phenotype, almost normal to mild lyso-Gb3 elevation, and mild clinical symptoms, despite low GLA activity. This is due to the structural features of the R112H GLA protein. We herein report the case of a 42-year-old male patient with late-onset FD with a R112H mutation. The patient exhibited only renal involvement with no other organ damage and was successfully treated with galactosidase beta and subsequent migalastat for approximately 10 years. Especially, migalastat was clinically effective in normalizing plasma lyso-Gb3 levels and inhibiting the progression of renal damage associated with FD. Therefore, the use of migalastat in the FD patients with R112H mutation is highly recommended based on this case report.

BACKGROUND: Long-term enzyme replacement therapy (ERT) may improve prognosis in the patients with Fabry disease (FD), however, detail psychosocial burden has not been focused on long life expectancy. We experienced a male case of FD under ERT, he was placed on hemodialysis and presented rapidly progressive cognitive function.
METHODS: A 51-year-old male patient with FD has been receiving ERT from age of 38 years. Hemodialysis was initiated at the age of 47 years. The patient experienced several attacks of cerebral infarction, and brain images demonstrated wide-spread asymptomatic ischemic lesions. His behavior became problematic at the age of 51 years. He often exhibited restlessness during hemodialysis sessions and failure to communicate effectively. The patient experienced impairment of attention and executive function, topographical disorientation, and amnesia. Consequently, it was necessary for medical staff and family members to monitor his behavior for safe extracorporeal circulation and daily life activities. Annual standardized neuropsychiatric testing revealed worsening of cognitive performance.
CONCLUSIONS: Despite treating with long-term ERT, it is necessary to determine the psychosocial burden derived from the progression of cognitive impairment in patients with FD undergoing hemodialysis.

Fabry disease (FD) is a rare, X-linked lysosomal storage disorder that can result in fatal end-stage renal disease, heart failure, and cerebro-occlusive events. Vague clinical symptoms and rarity often mean diagnosis and potential treatment is delayed. Ophthalmic findings in FD patients can be helpful in establishing an early diagnosis and timely treatment. Spectral domain optical coherence tomography (SD-OCT) imaging in FD patients shows hyper-reflective foci (HRF) in characteristic patterns within the inner retinal layers. We found that the HRF was localised in linear distributions at the deep and superficial borders of the retinal inner nuclear layer, likely reflecting anatomic vascular plexuses and FD-related sphingolipid deposition within the vessel walls. These results highlight the potential use of SD-OCT in FD and how it may aid diagnosis in undifferentiated patients, prognostication, and disease monitoring.

Fabry disease (FD) is an X-linked lysosomal storage disorder characterized by alpha-galactosidase A deficiency, resulting in globotriaosylceramide accumulation and diverse clinical manifestations. We report a case of a 22-year-old male presenting with cochleovestibular disorders as the initial FD manifestation, alongside a literature review. Diagnostic evaluation revealed reduced alpha-galactosidase A activity, confirming FD. Cochleovestibular involvement, although underexplored, significantly affects FD patients, often presenting with sudden deafness or sensorineural hearing loss. Prompt diagnosis and enzyme replacement therapy are crucial for managing FD. Otolaryngologists play a key role in early detection and intervention. This case underscores the importance of considering FD in cases of hearing loss, tinnitus, or vertigo, emphasizing the need for heightened awareness among healthcare providers.

Fabry disease (FD) is a rare X chromosome-linked disorder and can be easily misdiagnosed. Here, we report the case of a 69-year-old male patient with FD who developed heart failure and showed extremely high pulmonary artery pressure. His initial symptom was recurrent atrial fibrillation. The left and right atrial inner diameters were large, and the ventricular wall was thick. Gene analysis which showed GLA c.215T>C p.Met72Thr mutation and single photon emission computed tomography indicated the diagnosis of FD with coronary microvascular dysfunction. The patient was prescribed anti-heart failure drugs, including vericiguat. Following the treatment, his heart function and microvascular perfusion significantly improved, which might be due to the beneficial effects of vericiguat.

BACKGROUND: Fabry disease is a multisystemic disorder characterized by deposition of globotriaosylceramide (Gb3) and its deacylated form in multiple organs, sometimes localized in specific systems such as the nervous or cardiovascular system. As disease-modifying therapies are now available, early diagnosis is paramount to improving life quality and clinical outcomes. Despite the widespread use of non-invasive techniques for assessing organ damage, such as cardiac magnetic resonance imaging (MRI) for patients with cardiac disease, organ biopsy remains the gold standard to assess organ involvement.
METHODS: The cases of two patients, father and daughter with a W162C mutation, are described. The father presented with late-onset, cardiac Fabry disease, subsequently developing systolic dysfunction and heart failure. His daughter, while asymptomatic and with normal cardiac assessment (except for slightly reduced native T1 values by cardiac MRI), had already initial myocyte Gb3 deposits on the endomyocardial biopsy, allowing her to start therapy precociously and potentially modifying the course of her disease. A review of the literature concerning the W162C mutation is then provided, showing that it is usually associated to classic, multisystemic Fabry disease rather than the cardiac-restricted form as in these two cases.
CONCLUSIONS: Three main points can be concluded from this report. First, the W162C mutation can present with a more variegate phenotype than that predicted on a molecular basis. Second, endomyocardial biopsy was shown in this case to precede non-invasive investigation in determining organ involvement, justifying further studies on this potentially reliable technique, Third, difficulties can arise in the management of asymptomatic female carriers.

Fabry disease is a metabolic disorder caused by a deficiency in lysosomal enzymes and is inherited as an X-chromosomal disorder. Patients with Fabry disease have a low incidence of cancer, and reports of malignant tumors, especially in the thoracic region, are rare. In this case report, we describe our experience with radiation therapy following breast-conserving surgery in a patient with left breast cancer and Fabry disease, and we review the existing literature. The patient, a woman in her 40s, required postoperative irradiation for left breast cancer (pT1N0M0). There were several patients with Fabry disease in her family, and the diagnosis of Fabry disease was made five years ago. Cardiac function evaluation revealed no significant abnormalities, but a myocardial biopsy had suggested the presence of Fabry disease. Due to the relatively preserved distance between the heart and the chest wall, the patient received heart-shielded three-dimensional conformal radiation therapy at a dose of 53.2 Gy in 20 fractions, without the use of deep-inspiration breath-hold or intensity-modulated radiotherapy. After treatment was completed, only mild radiation dermatitis was observed. Six months have passed since treatment, and there have been no serious adverse events.

Fabry disease (FD) is an uncommon, X-linked, lysosomal storage disease that causes defects in the glycosphingolipid metabolic pathway due to deficient or absent lysosomal α-galactosidase (α-Gal A) activity. This leads to the accumulation of globotriaosylceramide (GL-3) within lysosomes in a wide range of cells, including endothelial, cardiac, renal, and corneal cells, and consequently, the progressive appearance of clinical symptoms in target organs. Enzyme replacement therapy (ERT), which involves the exogenous supplementation of α-Gal A enzyme and has been successfully administered for treating FD.Here, we report a case of a 37-year-old male with complaints of recurrent proteinuria and ventricular septal thickening. A renal biopsy revealed vacuolization and foamy changes in podocytes, and the presence of myelin-like bodies and zebra bodies. The white blood cell α-Gal A activity was very low, while the Lyso-GL-3 level was high. Additionally, genetic analysis revealed a gene variant c.902G > A p. Arg301Gln. The patient was diagnosed with FD, and subsequently received intravenous ERT with a dose of Agalsidase α (0.2 mg/kg, 17.5 mg every 2 weeks). Currently, the values of proteinuria and ventricular septum thickness remain stable during the 6-month follow-up. Initiating ERT at an early age can effectively decrease the deposition of GL-3, attenuate the progressive clinical manifestations of FD, and provide greater long-term benefits.