Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Fabry disease - a genetically conditioned extremely rare disease with a very unusual course.

ABSTRACT: Fabry disease (FD) is a rare lysosomal storage disease. FD is caused by the presence of a deleterious mutation in the GLA gene encoding the enzyme alpha galactosidase A (αGAL A) on the X chromosome. The accumulation of Gb3 and lyso-GL-3 in nerve fiber cells, endothelium, vascular muscle cells, mesangial cells, podocytes, renal tubular epithelial cells and cardiomyocytes is the most important pathogenetic factor. The rate of disease progression depends on residual conserved enzymatic activity. In this article we present an example of a 25-year-old patient with FD with an initial asymptomatic course. The first manifestation of FD developed in the third decade of life. These include high blood pressure, urinary changes and grade V renal failure, requiring renal replacement therapy. The diagnosis was made very late, when renal failure and cerebro-cardiac complications occurred, including stroke and dangerous cardiac tamponade.

SUBMITTER: Snit M

PROVIDER: S-EPMC8898388 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Fabry disease - a genetically conditioned extremely rare disease with a very unusual course.

Śnit Mirosław M Przyłudzka Marcela M Grzeszczak Władysław W

Intractable & rare diseases research 20220201 1

Fabry disease (FD) is a rare lysosomal storage disease. FD is caused by the presence of a deleterious mutation in the GLA gene encoding the enzyme alpha galactosidase A (αGAL A) on the X chromosome. The accumulation of Gb3 and lyso-GL-3 in nerve fiber cells, endothelium, vascular muscle cells, mesangial cells, podocytes, renal tubular epithelial cells and cardiomyocytes is the most important pathogenetic factor. The rate of disease progression depends on residual conserved enzymatic activity. In ...[more]

PMID: 35261850

Similar Datasets

Unusual Course of Lafora Disease.

Project description:A 42-year-old male was admitted for refractory status epilepticus. At the age of 25, he had been diagnosed with juvenile myoclonic epilepsy. He had a stable clinical course for over a decade until a recent deterioration of behavior and epilepsy. After exclusion of acquired disorders, diagnostic work-up included application of next-generation sequencing (NGS), with a gene panel targeting progressive myoclonic epilepsies. This resulted in the diagnosis Lafora disease resulting from compound heterozygous NHLRC1 pathogenic variants. Although these pathogenic variants may be associated with a variable phenotype, including both severe and mild clinical course, the clinical presentation of our patient at this age is very unusual for Lafora disease. Our case expands the phenotype spectrum of Lafora disease resulting from pathogenic NHLRC1 variants and illustrates the value of using NGS in clinical practice to lead to a rapid diagnosis and guide therapeutic options.

| S-EPMC5719837 | biostudies-literature

E-Learning for Rare Diseases: An Example Using Fabry Disease.

Project description:Rare diseases represent a challenge for physicians because patients are rarely seen, and they can manifest with symptoms similar to those of common diseases. In this work, genetic confirmation of diagnosis is derived from DNA sequencing. We present a tutorial for the molecular analysis of a rare disease using Fabry disease as an example. An exonic sequence derived from a hypothetical male patient was matched against human reference data using a genome browser. The missense mutation was identified by running BlastX, and information on the affected protein was retrieved from the database UniProt. The pathogenic nature of the mutation was assessed with PolyPhen-2. Disease-specific databases were used to assess whether the missense mutation led to a severe phenotype, and whether pharmacological therapy was an option. An inexpensive bioinformatics approach is presented to get the reader acquainted with the diagnosis of Fabry disease. The reader is introduced to the field of pharmacological chaperones, a therapeutic approach that can be applied only to certain Fabry genotypes. The principle underlying the analysis of exome sequencing can be explained in simple terms using web applications and databases which facilitate diagnosis and therapeutic choices.

| S-EPMC5666731 | biostudies-literature

Pericardial effusion in the course of Fabry disease cardiomyopathy: a case report.

Project description:BackgroundFabry disease (FD) is an X-chromosome-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity.Case summaryA 51-year-old Japanese woman with a previous diagnosis of FD presented with pericardial effusion. The exudative pericardial fluid contained globotriaosylsphingosine. Left ventricular hypertrophy progressed despite regular administration of agalsidase alfa every 2 weeks over a 7-year period, with increases in plasma levels of globotriaosylsphingosine and interleukin (IL)-18. In addition, the IL-6 level in the pericardial fluid was markedly higher than that in plasma.DiscussionThis case suggests that elevated IL-6 and IL-18 levels in pericardial fluid and plasma indicate the severity of FD cardiomyopathy.

| S-EPMC8557325 | biostudies-literature

Genetically Modified Cell Transplantation Through Macroencapsulated Spheroids with Scaffolds to Treat Fabry Disease.

Project description:Cell transplantation is expected to be another strategy to treat lysosomal diseases, having several advantages compared to enzyme replacement therapy, such as continuous enzyme secretion and one-time treatment to cure diseases. However, cell transplantation for lysosomal diseases holds issues to be resolved for the clinical field. In this study, we developed a new ex vivo gene therapy platform using a transplant pack, which consists of a porous membrane made of ethylene-vinyl alcohol in the pack-type and spheroids with scaffolds. These membranes have countless pores of less than 0.1 µm2 capable of secreting proteins, including alpha-galactosidase enzyme, and segregating the contents from the host immune system. When the packs were subcutaneously transplanted into the backs of green fluorescent protein (GFP) mice, no GFP-positive cells migrated to the transplanted pack in either autogenic or allogenic mice. The transplanted cells in the pack survived for 28 days after transplantation. When cells overexpressing alpha-galactosidase were used as donor cells for the packs and implanted into Fabry disease model mice, the accumulation of the alpha-galactosidase enzyme was also observed in the livers. In this study, we reported a new ex vivo therapeutic strategy combining macroencapsulation and cellular spheroids with scaffolds. This pack, macroencapsulated spheroids with scaffolds, can also be applied to other types of lysosomal diseases by modifying genes of interest.

| S-EPMC8842475 | biostudies-literature

'Caterpillar right ventricle': unusual manifestation of a rare disease.

Project description:A 66-year-old man presented with abdominal distension and pedal oedema for the past 10 years. He had history of right heart failure on several occasions in the past, and one of these admissions prompted referral to a cardiac specialist. On examination, he had markedly elevated jugular venous pressure with prominent 'y-descent', a tricuspid regurgitation murmur, gross ascites and pedal oedema. A full blood count, routine biochemical screen and serum bicarbonate levels were normal. Right ventricular angiogram revealed a 'caterpillar'-like aneurysm of the right ventricle (RV) apex (figure 1 arrow) with a dilated right ventricular outflow tract and significant tricuspid regurgitation with a dilated right atrium (see online supplementary video 1). Figure 1 Acine angiographic frame of the right ventricle in posteroanterior view, showing a 'caterpillar'-like right ventricle aneurysm (arrow). 10.1136/heartasia-2017-010957.supp3Supplementary file 3.QuestionOn the basis of the clinical and right ventriculography features, what is the most likely diagnosis for this patient?Arrhythmogenic right ventricular cardiomyopathy (ARVC)Right ventricular endomyocardial fibrosis (RV-EMF) with an RV aneurysmCardiac sarcoidosisCongenital diverticulum of the right ventricle.

| S-EPMC5692100 | biostudies-literature

Infective endocarditis uncovered a very rare congenital heart disease.

Project description:In this article, we introduced a case of rare congenital anomalies that was asymptomatic until adulthood and was complicated by infective endocarditis and dissection of aortic valve leaflet.

| S-EPMC8212014 | biostudies-literature

Unintended side effects of transformation are very rare

Project description:Received wisdom in the field of fungal biology holds that the process of editing a genome by transformation and homologous recombination is inherently mutagenic. However, that belief is based only on circumstantial evidence. We provide the first direct measurement of the effects of transformation on the genome by sequencing the genomes of 29 transformants and 30 untransformed controls to high coverage. Contrary to the received wisdom, our results show that transformation of DNA flanked by long targeting sequences, followed by homologous recombination and selection on a drug marker, is extremely safe. Gene deletion may select for a few mutations that occur after transformation, but even then we found fewer than two point mutations per gene deletion strain. We also tested these strains for changes in gene expression and found only a few genes that were consistently differentially expressed between wild types and strains with a drug resistance marker inserted. As part of this process, we provide the first published genome sequence of the commonly used laboratory strain Cryptococcus neoformans var. grubii strain KN99.

2017-09-26 | GSE104198 | GEO

Rare Copy Number Variation in Extremely Impulsively Violent Males

Project description:The Illumina Human Omni2.5 array is a high resolution microarray platform for studying copy number variations in the human genome. It is widely being used in both clinical and research settings for identifying causative variants as well as interrogating the genome for benign variants. We employed this platform to investigate the risk factor CNVs in 281 individuals diagnosed with Antisocial Personality Disorder.

2021-06-01 | GSE116022 | GEO

Natural course of Fabry disease with the p. Arg227Ter (p.R227*) mutation in Finland: Fast study.

Project description:BackgroundFabry disease is caused by a deficient or an absent alfa-galactosidase A activity and is an X-linked disorder that results in organ damage and a shortened life span, especially in males. The severity of the disease depends on the type of mutation, gender, skewed X-chromosome inactivation, and other still unknown factors.MethodsIn this article, we describe the natural course of a common classic Fabry disease mutation, p.Arg227Ter or p.R227*, in Finland.ResultsFour males and ten females belonged to two extended families. The mean age was 46 years (SD 18.4). Six patients (43%) had cardiac hypertrophy, three patients (21%) had ischemic stroke, and none had severe kidney dysfunction. Three patients had atrial fibrillation; two patients who had atrial fibrillation also had pacemakers. All males over 30 years of age had at least one of the following manifestations: cardiac hypertrophy, stroke, or proteinuria. In females, the severity of Fabry disease varied from classic multiorgan disease to a condition that mimicked the attenuated cardiac variant. No one was totally asymptomatic without any signs of Fabry disease. Cardiac magnetic resonance imaging was performed on nine of 14 patients was the most sensitive for detecting early cardiac manifestations. Five patients (55%) had late gadolinium enhancement-positive segments.ConclusionCardiac involvement should be effectively detected in females before considering them asymptomatic mutation carriers.

| S-EPMC6785458 | biostudies-literature

Sleep Disturbance, Obstructive Sleep Apnoea and Abnormal Periodic Leg Movements: Very Common Problems in Fabry Disease.

Project description:ObjectivesTo assess the prevalence of sleep disorder(s) in males with Fabry disease and explore possible association with disease phenotype.BackgroundFabry disease, an X-linked lysosomal storage disease caused by deficiency in α-galactosidase, results in intracellular accumulation of globotriaosylceramide. It causes organ dysfunction, most significantly affecting renal, cerebrovascular and cardiovascular systems. Respiratory involvement may include obstructive lung disease, reduced diffusing capacity and thickened soft and hard palates. Patients commonly develop small-fibre sensory peripheral neuropathy manifested by acroparaesthesia and pain crises. Combined with self-reported sleep disturbance and snoring, these features suggest an increased risk of sleep disorders.MethodsIn-laboratory polysomnography (PSG) studies and sleep inventory assessments, including Epworth Sleepiness Scale (ESS), were performed in a cohort of male Fabry patients. PSGs were reviewed by a sleep physician. Sleep-disordered breathing and periodic leg movements were targeted for analysis. Associations with renal, cardiovascular and cerebrovascular function were sought.ResultsTwenty males underwent overnight PSG. Patient baseline characteristics included age 43.9 ± 10.7 years, BMI 24.3 ± 3.8 kg/m2, neck circumference 39.7 ± 3.3 cm and ESS 9.8 ± 5.1 (7/20, abnormal ESS >10). Abnormal periodic leg movement index (PLMI) was present in 95% (mean frequency 42.4 ± 28.5/min) and sleep-disordered breathing in 50% patients. Periodic leg movements were associated with pain and depression but not with increased cortical arousal.ConclusionsSleep-disordered breathing and abnormal PLMI are highly prevalent in patients with FD. The presence of abnormal PLMI alone appears to have minimal impact on sleep disturbance, but is associated with depression and analgesic requirement.

| S-EPMC5272841 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data