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Current Problems in Cardiology Jan 2023Fabry disease (FD) is a rare, progressive, X-linked inherited disorder of glycosphingolipid metabolism. It is a monogenic disease due to α-galactosidase A (α-GAL)... (Review)
Review
Fabry disease (FD) is a rare, progressive, X-linked inherited disorder of glycosphingolipid metabolism. It is a monogenic disease due to α-galactosidase A (α-GAL) enzyme deficiency, leading to the accumulation of globotriaosylceramide (GL3) within lysosomes beginning in utero. Multiple systems are involved, most notably the vascular, renal, cardiac, and nervous systems. Early clinical manifestations include neuropathic pain, angiokeratomas, anhidrosis, cornea verticillata, and gastrointestinal symptoms. In the later stages, FD manifests with transient ischemic attacks, strokes, hearing loss, and life-threatening complications involving the kidneys and heart. Cardiac involvement in Fabry disease is typically characterized by increased left ventricular wall thickness/mass, functional abnormalities, valvular heart disease, arrhythmias, and heart failure. The life expectancy of the patient with untreated Fabry disease falls significantly once cardiac or renal manifestations develop. This review will focus on the cardiac manifestations of FD and the role of multimodality imaging in diagnosis and follow-up.
Topics: Humans; Fabry Disease; alpha-Galactosidase; Kidney; Stroke; Arrhythmias, Cardiac
PubMed: 36202174
DOI: 10.1016/j.cpcardiol.2022.101439 -
Birth Defects Research Mar 2022
Topics: Angiokeratoma; Humans; Limb Deformities, Congenital; Livedo Reticularis; Lower Extremity; Skin Diseases, Vascular; Skin Neoplasms; Telangiectasis
PubMed: 35150097
DOI: 10.1002/bdr2.1985 -
Frontiers in Medicine 2021Dermoscopic features of cutaneous vascular anomalies have been reported, but the described features currently known are limited and not well-understood. The aim of this...
Dermoscopic features of cutaneous vascular anomalies have been reported, but the described features currently known are limited and not well-understood. The aim of this study is to comprehensively summarize and compare the dermoscopic features of the four different types of cutaneous vascular anomalies [infantile hemangiomas (IH), cherry angioma (CA), angiokeratomas (AK), and pyogenic granuloma (PG)] in the Chinese Han population. Dermoscopic features of 31 IH, 172 CA, 31 AK, and 45 PG were collected based on the contact non-polarized mode of dermoscopy at 20-fold magnification. Dermoscopic features including background, lacunae, vessel morphology and distribution were collected and summarized. Additionally, we compared these features by age stage, gender, and anatomical locations in CA. The dermoscopic features of IH included the red lacunae, red/red-blue/red-white backgrounds, and vessel morphology such as linear curved vessels, serpiginous vessels, coiled vessels. For CA, the lacunae appeared reddish brown to reddish blue or only red. In terms of vascular morphology, serpentine vessels, coiled vessels, looped vessels, and curved vessels could be seen in the lesions. A few lesions were black or presented with a superficial white veil. There were statistical differences in red background ( = 0.021), unspecific vessel distribution ( = 0.030), black area ( = 0.029), and white surface ( = 0.042) among different age groups. Red-brown lacunae ( = 0.039), red-blue ( = 0.013), red-white background ( = 0.015), black area ( = 0.016), and white surface ( = 0.046) were of statistical difference in terms of the locations of lesions. Lacunae were also observed in AK, which presented with red, dark purple, dark blue, black. Global dermoscopic patterns that were characterized by a homogeneous area were obvious in all PG lesions, among which 30 (66.7%) were red-white and 15 (33.3%) were red. As for local features, "white rail" lines were detected in 19 (42.2%) lesions and white collarette was seen in 34 (75.6%) lesions. Dermoscopy is an applicable diagnostic tool for the diagnosis of cutaneous vascular anomalies. It is necessary to take into account the age stage and lesion location when we diagnose CA using dermoscopy.
PubMed: 34262918
DOI: 10.3389/fmed.2021.692060 -
Cureus Nov 2019In this study, we report a four-year-old male with D-2-hydroxyglutaric aciduria (D2HA) and enchondromatosis with a prior history of hyperpigmented, segmental whorls and...
In this study, we report a four-year-old male with D-2-hydroxyglutaric aciduria (D2HA) and enchondromatosis with a prior history of hyperpigmented, segmental whorls and streaks on his abdomen who later presented with an eruption of angiokeratoma circumscriptum within a similar distribution. His condition can likely be explained by underlying somatic mosaicism; however, a unifying culprit gene mutation has not yet been identified. To date, only 10 reported cases of D2HA with enchondromatosis are available in the literature with three reported skin findings. This is the first reported case of angiokeratoma circumscriptum associated with the rare condition of D2HA and enchondromatosis.
PubMed: 31890366
DOI: 10.7759/cureus.6157 -
Frontiers in Pediatrics 2023To summarize the clinical features, diagnosis and enzyme replacement therapy(ERT) of Fabry disease (FD) in children.
OBJECTIVE
To summarize the clinical features, diagnosis and enzyme replacement therapy(ERT) of Fabry disease (FD) in children.
METHODS
The clinical data, laboratory tests, genetic variations and treatment of 10 FD children diagnosed in Shandong Provincial Hospital from September 2020 to June 2022 were retrospectively analyzed.
RESULTS
Among the 10 cases from 6 families, 7 patients were boys of 4 to 13 years of age, and 3 were girls of 12 to 15 years of age. There were 7 symptomatic patients, including 6 boys and 1 girl. All 7 patients presented with acral neuralgia. Five patients had little or no sweating. Five patients presented with cutaneous angiokeratoma. Two patients had abdominal pain. One patient developed joint symptoms. Four patients had corneal opacity. One patient had hearing loss; one patient had short stature. One patient had mild proteinuria and 1 patient had dysplasia of the right kidney with decreased eGFR (55.28 ml/min.1.73 m). The left ventricular mass index was slightly elevated in 1 patient. Three patients had mild obstructive ventilatory dysfunction; a small amount of effusion in the intestinal space of the lower abdomen or mild fatty liver was found in 2 patients. Partial empty sella turcica in 1 patient. A total of 6 GLA gene variants were detected in 10 children, among which C.1059_1061delGAT (p.met353del) was a newly discovered mutation. Five children received ERT, of which 4 were treated with agalsidase beta and 1 was treated with agalsidase alpha. Only 1 patient had anaphylaxis. Lyso-GL-3 levels decreased significantly in the first 3 months of ERT initiation and remained relatively stable thereafter in 3 patients. The Lyso-GL-3 level was decreased, but renal impairment continued to progress in 1 patient treated with agalsidase alpha.
CONCLUSION
The clinical manifestations of FD in childhood are diverse, and it is necessary to make a definite diagnosis by combining family history, enzyme activity, biomarkers, gene testing and other indicators. Pedigree screening and high-risk population screening are helpful for early identification, early diagnosis and early treatment. No serious adverse reactions were found during the short-term treatment with agalsidase alpha and beta.
PubMed: 36816376
DOI: 10.3389/fped.2023.1084336 -
Molecular Genetics and Metabolism Aug 2020Fabry disease is an X-linked disease due to a deficiency of the lysosomal enzyme alpha-galactosidase A. Clinical symptoms in classically affected males include...
Fabry disease is an X-linked disease due to a deficiency of the lysosomal enzyme alpha-galactosidase A. Clinical symptoms in classically affected males include acroparesthesia, anhydrosis and angiokeratoma, which may present during childhood followed by cardiac, cerebral and renal complications. Even though pulmonary involvement is not widely appreciated by clinicians, an obstructive lung disease is another recognized component of Fabry disease. Coronavirus Disease-19 (COVID-19), caused by the SARS-CoV-2 virus was labeled as a global pandemic and patients with Fabry disease can be considered at high risk of developing severe complications. The impact of COVID-19 on patients with Fabry disease receiving enzyme replacement therapy is still unknown. Many patients who receive treatment in the hospital experienced infusion disruptions due to fear of infection. Effects of temporary treatment interruption was described in more detail in other lysosomal storage diseases, but the recommencement of therapy does not fully reverse clinical decline due to the temporary discontinuation. When possible, home-therapy seems to be the most efficient way to maintain enzyme replacement therapy access during pandemic. Sentence take-home message: Home-therapy, when possible, seems to be the most efficient way to maintain enzyme replacement therapy access during pandemic in patients with Fabry disease.
Topics: Adult; Betacoronavirus; COVID-19; Continuity of Patient Care; Coronavirus Infections; Enzyme Replacement Therapy; Fabry Disease; Female; Home Infusion Therapy; Humans; Infection Control; Infusions, Intravenous; Isoenzymes; Lung Diseases, Obstructive; Male; Middle Aged; Pandemics; Pneumonia, Viral; Recombinant Proteins; SARS-CoV-2; Severity of Illness Index; Time Factors; alpha-Galactosidase
PubMed: 32561366
DOI: 10.1016/j.ymgme.2020.06.002 -
Indian Journal of Dermatology,...
Topics: Child; Humans; Angiokeratoma; Immunosuppressive Agents; Skin Neoplasms; Sirolimus
PubMed: 37436014
DOI: 10.25259/IJDVL_1008_2022 -
Eplasty 2022Angiokeratomas are vascular neoplasms with hyperkeratotic red to black papules and plaques, which may present as solitary or multiple lesions with variations in color,...
Angiokeratomas are vascular neoplasms with hyperkeratotic red to black papules and plaques, which may present as solitary or multiple lesions with variations in color, shape, and location. Successful treatment not only involves improvement of these symptoms but also cosmetic improvement. This report reviews 2 cases of cutaneous angiokeratoma treated with surgical excision and a 595-nm pulsed dye laser (PDL) in which the patients showed improvement of symptoms and cosmetic appearance. There are various types of angiokeratomas, and their extent, size, condition, and symptoms are different. Therefore, lesion-specific combined treatments may yield better results.
PubMed: 36545640
DOI: No ID Found -
BMC Medical Genomics Aug 2021Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase (FUCA1) activity, leading to the accumulation of fucose-containing...
BACKGROUND
Fucosidosis is an autosomal recessive lysosomal storage disease caused by defective alpha-L-fucosidase (FUCA1) activity, leading to the accumulation of fucose-containing glycolipids and glycoproteins in various tissues. Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, and dysostosis multiplex.
METHODS
All exons and flanking intron regions of FUCA1 were screened by direct sequencing to identify mutations and polymorphisms in three unrelated families with fucosidosis. Bioinformatics tools were then used to predict the impacts of novel alterations on the structure and function of proteins. Furthermore, the identified mutations were localized onto a 3D structure model using the DeepView Swiss-PdbViewer 4.1 software, which established a function-structure relationship of the FUCA1 proteins.
RESULTS
Four novel mutations were identified in this study. Two patients (P1 and P2) in Families 1 and 2 who had the severe phenotype were homoallelic for the two identified frameshift mutations p.K57Sfs*75 and p.F77Sfs*55, respectively. The affected patient (P3) from Family 3, who had the milder phenotype, was heterozygous for the novel missense mutation p.G332E and the novel splice site mutation c.662+5g>c. We verified that this sequence variation did not correspond to a polymorphism by testing 50 unrelated individuals. Additionally, 16 FUCA1 polymorphisms were identified. The structure prediction analysis showed that the missense mutation p.G332E would probably lead to a significant conformational change, thereby preventing the expression of the FUCA1 protein indeed; the 3D structural model of the FUCA1 protein reveals that the glycine at position 332 is located near a catalytic nucleophilic residue. This makes it likely that the enzymatic function of the protein with p.G332E is severely impaired.
CONCLUSION
These are the first FUCA1 mutations identified in Tunisia that cause the fucosidosis disease. Bioinformatics analysis allowed us to establish an approximate structure-function relationship for the FUCA1 protein, thereby providing better genotype/phenotype correlation knowledge.
Topics: alpha-L-Fucosidase
PubMed: 34425818
DOI: 10.1186/s12920-021-01061-3 -
Dermatologic Therapy Nov 2020Angiokeratomas are benign vascular neoplasms that arise as solitary or multiple lesions, most commonly treated with excision, electrodessication, cryotherapy, or laser...
Angiokeratomas are benign vascular neoplasms that arise as solitary or multiple lesions, most commonly treated with excision, electrodessication, cryotherapy, or laser therapies. This case presents a young female whose solitary angiokeratoma was treated with topical 1% sirolimus cream, improving the appearance, symptoms, and size of the lesion. Topical sirolimus cream may be a noninvasive treatment option for angiokeratomas with fewer risks than standard therapy that may be feasible and preferable for some patients.
Topics: Angiokeratoma; Female; Humans; Laser Therapy; Sirolimus; Skin Neoplasms
PubMed: 32594609
DOI: 10.1111/dth.13907