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Skin Therapy Letter Mar 2018Fabry disease (FD) is an X-linked lysosomal storage disease. A lack of alpha-galactosidase activity results in the accumulation of globotriaosylceramide in cells of... (Review)
Review
Fabry disease (FD) is an X-linked lysosomal storage disease. A lack of alpha-galactosidase activity results in the accumulation of globotriaosylceramide in cells of various systems, leading to multi-systemic effects. The cutaneous hallmark of FD is a specific distribution of angiokeratoma. Other common symptoms include cornea verticillata, acroparesthesia, and sweating abnormalities. FD-specific symptoms, history, as well as examination of angiokeratoma can assist in the differential diagnosis. Enzyme replacement therapy is the current mainstay of treatment.
Topics: Fabry Disease; Humans; Randomized Controlled Trials as Topic
PubMed: 29562089
DOI: No ID Found -
Revista Da Associacao Medica Brasileira... Jan 2020Fabry disease (FD) is a recessive monogenic inheritance disease linked to chromosome X, secondary to mutations in the GLA gene. Its prevalence is estimated between... (Review)
Review
Fabry disease (FD) is a recessive monogenic inheritance disease linked to chromosome X, secondary to mutations in the GLA gene. Its prevalence is estimated between 1:8,454 and 1:117,000 among males and is probably underdiagnosed. Mutations in the GLA gene lead to the progressive accumulation of globotriaosylceramide (Gb3). Gb3 accumulates in lysosomes of different types of cells of the heart, kidneys, skin, eyes, central nervous system, and gastrointestinal system, and may lead to different clinical scenarios. The onset of symptoms occurs during childhood, with acroparesthesia, heat intolerance, and gastrointestinal symptoms, such as nausea, vomiting, abdominal pain, and neuropathic pain. Subsequently, symptoms related to progressive impairment appear, such as angiokeratomas, cornea verticillata, left ventricular hypertrophy, myocardial fibrosis, proteinuria, and renal insufficiency. The latter being the main cause of death in FD. The gold standard for diagnosis is the genetic analysis in search of mutation, in addition to family history. In homozygous patients, the enzyme activity can also be used. Once the diagnosis is confirmed, the patient and their family should receive genetic counseling. The treatment, in turn, currently focuses mainly on replacing the enzyme that is absent or deficient by means of enzyme replacement therapy, with the purpose of avoiding or removing deposits of Gb3. Chaperones can also be used for the treatment of some cases. It is considered that the specific treatment should be initiated as soon as a diagnosis is obtained, which can change the prognosis of the disease.
Topics: Enzyme Replacement Therapy; Fabry Disease; Female; Humans; Kidney; Male; Renal Insufficiency, Chronic; Trihexosylceramides
PubMed: 31939530
DOI: 10.1590/1806-9282.66.S1.10 -
Orphanet Journal of Rare Diseases Nov 2010Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is... (Review)
Review
Fabry disease (FD) is a progressive, X-linked inherited disorder of glycosphingolipid metabolism due to deficient or absent lysosomal α-galactosidase A activity. FD is pan-ethnic and the reported annual incidence of 1 in 100,000 may underestimate the true prevalence of the disease. Classically affected hemizygous males, with no residual α-galactosidase A activity may display all the characteristic neurological (pain), cutaneous (angiokeratoma), renal (proteinuria, kidney failure), cardiovascular (cardiomyopathy, arrhythmia), cochleo-vestibular and cerebrovascular (transient ischemic attacks, strokes) signs of the disease while heterozygous females have symptoms ranging from very mild to severe. Deficient activity of lysosomal α-galactosidase A results in progressive accumulation of globotriaosylceramide within lysosomes, believed to trigger a cascade of cellular events. Demonstration of marked α-galactosidase A deficiency is the definitive method for the diagnosis of hemizygous males. Enzyme analysis may occasionnally help to detect heterozygotes but is often inconclusive due to random X-chromosomal inactivation so that molecular testing (genotyping) of females is mandatory. In childhood, other possible causes of pain such as rheumatoid arthritis and 'growing pains' must be ruled out. In adulthood, multiple sclerosis is sometimes considered. Prenatal diagnosis, available by determination of enzyme activity or DNA testing in chorionic villi or cultured amniotic cells is, for ethical reasons, only considered in male fetuses. Pre-implantation diagnosis is possible. The existence of atypical variants and the availability of a specific therapy singularly complicate genetic counseling. A disease-specific therapeutic option - enzyme replacement therapy using recombinant human α-galactosidase A - has been recently introduced and its long term outcome is currently still being investigated. Conventional management consists of pain relief with analgesic drugs, nephroprotection (angiotensin converting enzyme inhibitors and angiotensin receptors blockers) and antiarrhythmic agents, whereas dialysis or renal transplantation are available for patients experiencing end-stage renal failure. With age, progressive damage to vital organ systems develops and at some point, organs may start to fail in functioning. End-stage renal disease and life-threatening cardiovascular or cerebrovascular complications limit life-expectancy of untreated males and females with reductions of 20 and 10 years, respectively, as compared to the general population. While there is increasing evidence that long-term enzyme therapy can halt disease progression, the importance of adjunctive therapies should be emphasized and the possibility of developing an oral therapy drives research forward into active site specific chaperones.
Topics: Adult; Cardiovascular Diseases; Child; Child, Preschool; Chromosomes, Human, X; Enzyme Replacement Therapy; Fabry Disease; Female; Humans; Kidney; Kidney Diseases; Male; Randomized Controlled Trials as Topic; alpha-Galactosidase
PubMed: 21092187
DOI: 10.1186/1750-1172-5-30 -
Dermatology Online Journal Nov 2020Angiokeratoma circumscriptum is the rarest variant of angiokeratoma. It usually affects females and it is characterized by dark-red to blue-black confluent papules or...
Angiokeratoma circumscriptum is the rarest variant of angiokeratoma. It usually affects females and it is characterized by dark-red to blue-black confluent papules or nodules on lower limbs in a segmental and unilateral distribution. We describe the clinical and histopathological findings in a patient with angiokeratoma circumscriptum and discuss the etiology, associations, diagnosis, differential diagnosis, and treatment.
Topics: Adult; Angiokeratoma; Diagnosis, Differential; Female; Humans; Lower Extremity; Skin Neoplasms
PubMed: 33342183
DOI: No ID Found -
Cureus Mar 2018Genital rejuvenation is applicable not only to women (vaginal rejuvenation) but also to men (scrotal rejuvenation). There is an increased awareness, reflected by the... (Review)
Review
Genital rejuvenation is applicable not only to women (vaginal rejuvenation) but also to men (scrotal rejuvenation). There is an increased awareness, reflected by the number of published medical papers, of vaginal rejuvenation; however, rejuvenation of the scrotum has not received similar attention in the medical literature. Scrotal rejuvenation includes treatment of hair-associated scrotal changes (alopecia and hypertrichosis), morphology-associated scrotal changes (wrinkling and laxity), and vascular-associated scrotal changes (angiokeratomas). Rejuvenation of the scrotum potentially may utilize medical therapy, such as topical minoxidil and oral finasteride, for scrotal alopecia and conservative modalities, such as depilatories and electrolysis, for scrotal hypertrichosis. Lasers and energy-based devices may be efficacious for scrotal hypertrichosis and scrotal angiokeratomas. Surgical intervention is the mainstay of therapy for scrotal laxity; however, absorbable suspension sutures are postulated as a potential intervention to provide an adequate scrotal lift. Hair transplantation for scrotal alopecia and injection of botulinum toxin into the dartos muscle for scrotal wrinkling are hypothesized as possible treatments for these conditions. The interest in scrotal rejuvenation is likely to increase as men and their physicians become aware of both the conditions of the scrotum that may warrant rejuvenation and the potential treatments of the scrotum for these individuals.
PubMed: 29755912
DOI: 10.7759/cureus.2316 -
Dermatologie (Heidelberg, Germany) Apr 2023Genodermatoses are a group of inherited skin diseases whose diagnosis is challenging due to their rarity as well as their clinical and genetic diversity. The majority... (Review)
Review
Genodermatoses are a group of inherited skin diseases whose diagnosis is challenging due to their rarity as well as their clinical and genetic diversity. The majority of genodermatoses are autosomal or X‑linked inherited, but mosaic forms are also observed. Genodermatoses comprise various phenotypes ranging from limited cutaneous disease to severe cutaneous and extracutaneous involvement and may also be early warning signs of a multisystemic disorder. Despite recent advances in genetic technology and skin imaging modalities, dermoscopy can be useful for screening, diagnosis, and treatment follow-up. In ectopic mineralization and lysosomal storage disorders (pseudoxanthoma elasticum and Fabry disease, respectively), cutaneous manifestations may indicate involvement of other organs. In keratinization diseases (e.g., ichthyoses) and acantholytic skin fragility disorders (e.g., Darier and Hailey-Hailey disease), dermoscopy may help to assess treatment response by visualizing background erythema, hyperkeratosis, and interkeratinocyte space prominence. Dermoscopy is a noninvasive, easily accessible, useful, in vivo assessment tool that is well established in dermatology to recognize characteristic features of genodermatoses.
Topics: Humans; Dermoscopy; Skin; Ichthyosis; Keratosis; Pemphigus, Benign Familial
PubMed: 36882583
DOI: 10.1007/s00105-023-05124-7 -
Anales de Pediatria Apr 2024
PubMed: 38580593
DOI: 10.1016/j.anpede.2024.03.048