Identification of mutations in Colombian patients affected with Fabry disease

Uribe, Alfredo; Mateus, Heidi; Prieto, Juan Carlos; Palacios, Maria Fernanda; Ospina, Sandra; Pasqualim, Gabriela; Matte, Úrsula da Silveira; Giugliani, Roberto

doi:10.1016/j.gene.2015.08.018

Cited by 9 publications

(11 citation statements)

References 44 publications

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“…For this reason, enzyme activity is too low or undetectable in male patients who have GLA mutation. To date, more than 600 mutations have been described in FD (Uribe et al 2015). FD is characterized by neutral glycosphingolipid, especially globotriaosylceramide (Gb 3 ), accumulation in lysosomes, due to lack of AGALA enzyme.…”

Section: Discussionmentioning

confidence: 99%

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Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey

et al. 2016

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Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal alpha-galactosidase A (AGALA) activity. FD and familial Mediterranean fever (FMF) have typical clinical similarities, and both diseases may progress to end-stage renal diseases. In this study, we aimed to determine the prevalence of FD in patients with FMF from Central Anatolia of Turkey. The study group consisted of 177 FMF patients, followed up by the Adult and Pediatric Nephrology Clinic of Cumhuriyet University Hospital. Screening for AGALA activity was performed by the dry blood spot method. Mutation analysis for GLA gene was carried out for patients having an AGALA enzyme activity value lower than the normal reference value. Low AGALA activity was detected in 23 (13 %) patients. Heterozygous GLA gene mutation c.[937G>T] p.[D313Y] was detected in one female patient (0.56 %). The patient was a 53-year-old female with proteinuria and who had undergone left nephrectomy; her glomerular filtration rate (GFR) by scintigraphy was found to be 70 ml/min. She had M694V mutation and no clinical manifestation of FD. In our study, the prevalence rate of FD was found as 0.56 % in FMF patients. The similarities between the symptoms of FMF and FD might lead to a diagnostic dilemma in physicians at countries where FMF is observed frequently. Although the prevalence of FD is rare, physicians should keep in mind that FD has an ambiguous symptomology pattern of FMF.

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Section: Discussionmentioning

confidence: 99%

“…Thus far, more than 600 GLA mutations have been identified. These mutations consist of missense mutations, nonsense mutations, and splice-site mutations as well as gene rearrangements (Uribe et al 2015).…”

Section: Introductionmentioning

confidence: 99%

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey

et al. 2016

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“…Patients with variant forms typically present milder clinical manifestations, mostly limited to the heart or the kidneys. These comprise almost 70% of all FD cases [10]. Progressive hypertrophic cardiomyopathy and fibrosis can result in various cardiac complications, including heart failure, arrhythmias, conduction abnormalities, and atrial fibrillation.…”

Section: Introductionmentioning

confidence: 99%

Genotype–Phenotype Correlation in a New Fabry-Disease-Causing Mutation

et al. 2019

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Background: Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by α-galactosidase A deficiency leading to intracellular glycosphingolipid accumulation. FD manifestation is multisystem, and can differ depending on disease-related genetic variants. Currently, more than 700 different FD-causing mutations have been identified in the human GLA gene. We identified a novel mutation in a Lithuanian family with classical manifestations of Fabry disease, revealing severe effects to the cardiovascular systems of heterozygous women. Case presentation: A 49-year-old woman underwent echocardiography due to progressive dyspnea that lasted seven years, reduced physical activity, and periodic cardiac arrhythmia. Echocardiography revealed left ventricular hypertrophy with normal diastolic function. The patient had experienced acroparesthesia in her upper limbs and abdominal pain since childhood, and in the last decade had experienced mild proteinuria without renal failure. Her renal biopsy was typical for Fabry disease. The patient’s brain magnetic resonance imaging (MRI) (T2 flair) showed white matter hyperintensities lesions. DNA sequencing of the proband, her mother and one of her sons showed a novel GLA gene exon 2 mutation, c.270C>G (p.Cys90Trp). All three patients had decreased α-galactosidase A activity and specific FD manifestations. Conclusions: A novel GLA mutation, c.270C>G (p.Cys90Trp), was found in a Lithuanian family with a classical form of Fabry disease in heterozygous women with predominant cardiac involvement. However, the exact manifestation of this mutation is still unclear as it is newly reported and further research must be done.

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“…According to previous reports, the clinical manifestations in the classic form of FD starting from childhood or adolescence include severe symptoms such as acroparesthesia, hypohidrosis, corneal opacities, stroke, cardiac abnormalities, and renal disorders with high mortality [3–5]. On the contrary, the clinical manifestations of the variant form comprising almost 70 % of FD patients [6] are usually mild and limited to the heart or kidney [3, 4]. Due to mild symptoms, these patients are often found after disease progression.…”

Section: Introductionmentioning

confidence: 99%

“…They only show findings of focal segmental glomerular sclerosis. For such cases, the key pathognomonic features such as electron-dense multi-lamellar inclusions can be obscured by extensive sclerosis on renal biopsy [4, 6]. As a result, it can be difficult to diagnose FD in time, particularly its variant form which is often undiagnosed or misdiagnosed as other heart or kidney diseases [4].…”

Section: Introductionmentioning

confidence: 99%

Identification of a novel GLA mutation (Y88C) in a Korean family with Fabry nephropathy: a case report

et al. 2016

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BackgroundFabry disease is a rare X-linked lysosomal storage disorder caused by α-galactosidase A deficiency. With the advancement of molecular diagnostic tools, more disease-causing mutations in α-galactosidase A (GLA) have been identified in Fabry disease. We found a novel mutation in a Korean family with predominant renal manifestations of the disease.Case presentationA 24-year-old man who wanted to donate a kidney to his 28-year-old brother with end-stage renal disease of unknown cause was evaluated. The 24-year-old man underwent percutaneous renal biopsy because of an accidentally found proteinuria. Electron microscopy of his renal biopsy showed numerous electron-dense multi-lamellar inclusions in the epithelial cytoplasm, typical for Fabry disease. Clinical and laboratory evaluation including the assessment of GLA enzyme activity and direct DNA sequencing in four members of the family were performed. Renal biopsy findings in the two affected male patients were described. Re-evaluation of a renal biopsy specimen of his 28-year-old brother obtained when he was diagnosed with renal failure revealed a very focal area of suspicious multilamellated structures in the Bowman’s space. DNA sequencing on the young man, his brother, and his mother revealed a novel GLA gene mutation, c.263A > G (p.Tyr88Cys). The three all showed decreased α-galactosidase A activity.ConclusionA novel GLA mutation, c.263A > G (p.Tyr88Cys), was found in a Korean family with predominant renal manifestations of Fabry disease.

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Identification of mutations in Colombian patients affected with Fabry disease

Cited by 9 publications

References 44 publications

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey

Prevalence of Fabry Disease in Familial Mediterranean Fever Patients from Central Anatolia of Turkey

Genotype–Phenotype Correlation in a New Fabry-Disease-Causing Mutation

Identification of a novel GLA mutation (Y88C) in a Korean family with Fabry nephropathy: a case report

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