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Datensatz: fabry:2821332
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: fabry:2821332
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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Datensatz: gaucher:18228687
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Boys with Duchenne muscular dystrophy (DMD) have DMD gene mutations, with associated loss of the dystrophin protein and progressive muscle degeneration and weakness. Corticosteroids and palliative support are currently the best treatment options. The long-term benefits of recently approved compounds such as eteplirsen and ataluren remain to be seen. Dogs with naturally occurring dystrophinopathies show progressive disease akin to that of DMD. Accordingly, canine DMD models are useful for studies of pathogenesis and preclinical therapy development. A dystrophin-deficient, male border collie dog was evaluated at the age of 5 months for progressive muscle weakness and dysphagia. Dramatically increased serum creatine kinase levels (41,520 U/L; normal range 59-895 U/L) were seen on a biochemistry panel. Histopathologic changes characteristic of dystrophinopathy were seen. Dystrophin was absent in the skeletal muscle on immunofluorescence microscopy and western blot. Whole genome sequencing, polymerase chain reaction, and Sanger sequencing revealed a frameshift, single nucleotide deletion in canine DMD exon 20, position 27,626,466 (c.2841delT mRNA), resulting in a stop codon six nucleotides downstream. Semen was archived for future line perpetuation. This spontaneous canine dystrophinopathy occurred due to a novel mutation in the minor DMD mutation hotspot (between exons 2 through 20). Perpetuating this line could allow for preclinical testing of genetic therapies targeted to this area of the DMD gene.
Auszug in der Originalsprache. Mata López S, Hammond JJ, Rigsby MB, Balog-Alvarez CJ, Kornegay JN, Nghiem PP. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: duchenne:29843823
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: duchenne:11475588
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Currently there is no systematic review and meta-analysis of the global incidence rates of anaphylactic and nonanaphylactic reactions to SARS-CoV-2 vaccines in the general adult population. To estimate the incidence rates of anaphylactic and nonanaphylactic reactions after COVID-19 vaccines and describe the demographic and clinical characteristics, triggers, presenting signs and symptoms, treatment and clinical course of confirmed cases. A systematic review and meta-analysis. Preferred Reporting Items for Systematic Reviews and Meta-Analyses [PRISMA] statement was followed. Electronic databases (Proquest, Medline, Embase, Pubmed, CINAHL, Wiley online library, and Nature) were searched from 1 December 2020 to 31 May 2021 in the English language using the following keywords alone or in combination: anaphylaxis, non-anaphylaxis, anaphylactic reaction, nonanaphylactic reaction, anaphylactic/anaphylactoid shock, hypersensitivity, allergy reaction, allergic reaction, immunology reaction, immunologic reaction, angioedema, loss of consciousness, generalized erythema, urticaria, urticarial rash, cyanosis, grunting, stridor, tachypnoea, wheezing, tachycardia, abdominal pain, diarrhea, nausea, vomiting and tryptase. We included studies in adults of all ages in all healthcare settings. Effect sizes of prevalence were pooled with 95% confidence intervals (CIs). To minimize heterogeneity, we performed sub-group analyses. Of the 1,734 papers that were identified, 26 articles were included in the systematic review (8 case report, 5 cohort, 4 case series, 2 randomized controlled trial and 1 randomized cross-sectional studies) and 14 articles (1 cohort, 2 case series, 1 randomized controlled trial and 1 randomized cross-sectional studies) were included in meta-analysis. Studies involving 26,337,421 vaccine recipients [Pfizer-BioNTech (n = 14,505,399) and Moderna (n = 11,831,488)] were analyzed. The overall pooled prevalence estimate of anaphylaxis to both vaccines was 5.0 (95% CI 2.9
Auszug in der Originalsprache. Alhumaid S, Al Mutair A, Al Alawi Z, Rabaan AA, Tirupathi R, Alomari MA, Alshakhes AS, Alshawi AM, Ahmed GY, Almusabeh HM, Alghareeb TT, Alghuwainem AA, Alsulaiman ZA, Alabdulmuhsin MA, AlBuwaidi EA, Dukhi AKB, Mufti HN, Al-Qahtani M, Dhama K, Al-Tawfiq JA, Al-Omari A. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: hae:34656181
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
X-chromosomal inheritance patterns and generally rare occurrence of Fabry disease (FD) account for mono-mutational hemizygous male and heterozygous female patients. Female mutation carriers are usually clinically much less severely affected, which has been explained by a suggested mosaicism in cell phenotype due to random allele shutdown. However, clinical evidence is scarce and potential additional effects in female gene carriers, which might account for specific clinical characteristics such as less severe chronic kidney disease, are yet unknown. This article reports on a 45 year old female patient carrying the two alpha-galactosidase A gene mutations c.416A > G, p.N139S in exon 3 and c.708G > C, p.W236C in exon 5, but still showing only mild organ manifestations. This current case highlights the importance of careful clinical characterization in patients with Fabry disease, who may show additional rare constellations and, therefore, are in need of personalized medicine. The impact of potential additional protective effects exceeding the presence of a non-pathogenic GLA allele in female gene carriers requires further investigation.
Auszug in der Originalsprache. Oder D, Vergho D, Ertl G, Wanner C, Nordbeck P. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: fabry:27431810
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
While cerebral lesions are common in Fabry disease (FD), spinal lesions have not been described, and their presence was suggested to be indicative of multiple sclerosis. Here, we present a FD patient with histopathological confirmed spinal ischemic stroke. A patient with genetically and biochemically diagnosed FD and characteristic manifestations (acroparesthesia, angiokeratomas, hypohidrosis, microalbuminuria, myocardial hypertrophy) presented with paraplegia, loss of all sensory modalities below Th9, and loss of bowel and bladder function. While cranial MRI was inconspicuous, spinal MRI showed a T2 hyperintense, non-contrast-enhancing lesion of the thoracic spinal cord. Lumbar puncture revealed mild pleocytosis, increased total protein and lactate levels, decreased glucose ratio, and negative oligoclonal bands. Rheumatic, neoplastic, and infectious disorders were excluded. The patient received intravenous and intrathecal methylprednisolone, plasmapheresis, intravenous immunoglobulins, and cyclophosphamide without clinical improvement. A biopsy of the thoracic lesion was performed. A histopathological examination revealed necrotic tissue consistent with spinal cord ischemia. Diagnostic work-up for stroke etiology clarification was not conspicuous. Two years onward, the patient suffered from a pontine infarction and a transient ischemic attack. The current case highlights the possible occurrence of spinal ischemic lesions in FD. Thus, the diagnosis of FD should not be prematurely discarded in the presence of spinal lesions.
Auszug in der Originalsprache. Krämer J, Glaser F, Hasselblatt M, Brand E, Pogoda C, Lenders M, Wiendl H, Meuth SG, Duning T. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
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Datensatz: fabry:33381118
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: hae:22584192
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: hae:26341649
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Duchenne muscular dystrophy is a progressive and lethal X-linked recessive neuromuscular disease caused by mutations in the dystrophin gene. It has a high rate of diagnostic delay; early diagnosis and treatment are often not possible due to delayed recognition of muscle weakness and lack of effective treatments. Current treatments based on genetic therapy can improve clinical results, but treatment must begin as early as possible before significant muscle damage. Therefore, early diagnosis and rehabilitation of Duchenne muscular dystrophy are needed before symptom aggravation. Creatine kinase is a diagnostic marker of neuromuscular disorders. Herein, the authors report a case of an infant patient with Duchenne muscular dystrophy with a highly elevated creatine kinase level but no obvious symptoms of muscle weakness. The patient was diagnosed with Duchenne muscular dystrophy via next-generation sequencing and chromosomal microarray analysis to identify possible inherited metabolic and neuromuscular diseases related to profound hyperCKemia. The patient is enrolled in a rehabilitation program and awaits the approval of the genetic treatment in Korea. This is the first report of an infantile presymptomatic Duchenne muscular dystrophy diagnosis using next-generation sequencing and chromosomal microarray analysis.
Auszug in der Originalsprache. Park EW, Shim YJ, Ha JS, Shin JH, Lee S, Cho JH. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: duchenne:34064562
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Fabry disease (FD) is an X-linked lysosomal storage disorder caused by mutations of the GLA gene, followed by deficiency in α-galactosidase A (α-gal) activity. Nephrotic syndrome, as the renal phenotype of FD, is unusual. Here, we report the rare case of a patient with FD with nephrotic syndrome whose proteinuria disappeared by immunotherapy. A 67-year-old Japanese man was admitted to our hospital because of emesis, abdominal pain, and facial edema due to nephrotic syndrome. The patient was diagnosed with focal segmental glomerulosclerosis (FSGS) by renal biopsy before being diagnosed with FD, and immunotherapy was initiated. After treatment, the kidney biopsy results showed typical glycosphingolipid accumulation in the podocytes of this patient. The white blood cell α-gal activity was very low, and genetic analysis revealed a GLA gene variant (M296I), which is known as a late-onset genetic mutation of FD. Immunotherapy (steroids and cyclosporine A) dramatically improved the massive proteinuria. Currently, he has been undergoing enzyme replacement therapy, and his proteinuria has further decreased. There is the possibility that other nephrotic syndromes, such as minimal change nephrotic syndrome or FSGS, may co-exist in this patient. We experienced the rare case of a FD patient whose nephrotic syndrome disappeared by immunotherapy. These findings suggest that immunosuppressive treatment may be considered if nephrotic syndrome develops, even in patients with FD.
Auszug in der Originalsprache. Fujisawa H, Nakayama Y, Nakao S, Yamamoto R, Kurokawa Y, Nakamura N, Nagata A, Tsukimura T, Togawa T, Sakuraba H, Fukami K. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: fabry:31847900
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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. Conclusion: 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.
Auszug in der Originalsprache. Čerkauskaitė A, Čerkauskienė R, Miglinas M, Laurinavičius A, Ding C, Rolfs A, Vencevičienė L, Barysienė J, Kazėnaitė E, Sadauskienė E. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: fabry:31067829
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
One out of seven patients with severe aortic stenosis (AS) undergoing transcatheter aortic valve replacement (TAVR) may be affected by transthyretin cardiac amyloidosis (ATTR-CA), mostly presenting with low-flow low-gradient AS with mildly reduced ejection fraction. The complex interaction of these two pathologies poses specific diagnostic and management challenges. The prognostic implications of this clinical intersection are not defined yet. Moreover, whether TAVR may have a prognostic benefit in ATTR-CA patients with symptomatic severe AS remains unclear, posing doubts on the best management strategy in this increasingly recognized subset of patients. We present a case of an 87-year old man with low-flow low-gradient severe AS, for whom a diagnosis of ATTR-CA was suspected based on clinical and echocardiographic criteria specific to coexisting AS and ATTR-CA. The diagnosis was eventually confirmed by positive bone tracer scintigraphy imaging. Following in-depth Heart team discussion, integrating frailty and prognostic information from combined cardiomyopathy states, a decision was made to manage the patient's severe AS conservatively. In the presented case, we deemed the natural history of ATTR-CA amyloidosis to negatively affect both the patient' prognosis and procedural risk, adversing TAVR indication despite symptomatic severe AS. No clear evidence is currently available to guide decision making in this setting, advocating for prospective studies to clarify if TAVR may have a prognostic benefit in ATTR-CA - and which ATTR-CA - patients.
Auszug in der Originalsprache. Gallone G, Landra F, D'Ascenzo F, Conrotto F, Casoni R, Bruno F, Omedè P, Alunni G, Andreis A, Vairo A, Giorgi M, Fava A, De Ferrari GM. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: fac:32487051
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: gaucher:12812317
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: duchenne:26091215
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: gaucher:7425777
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Renal phospholipidosis is a rare cause of proteinuria and kidney dysfunction. We describe a kidney transplant recipient who presented with slowly rising serum creatinine, nephrotic range proteinuria, and lower extremity edema 10 years post transplant. He was diagnosed with renal phospholipidosis on the transplant kidney biopsy. Patient did not have prior history or current symptoms or signs of Fabry disease. Serum α-galactosidase level was normal. The etiology was suspected to be due to chronic use of sertraline, a previously reported cause of drug-induced renal phospholipidosis. Sertraline was discontinued, and proteinuria declined with stabilization of kidney function at 6-months follow-up.
Auszug in der Originalsprache. Naseer MS, Chand R, Coppola S, Abreo A, Sharma M, Singh N. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: fabry:32566446
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Duchenne muscular dystrophy is the most common muscle disease found in male children. Currently, there is no effective therapy available for Duchenne muscular dystrophy patients. Therefore, it is essential to make a prenatal diagnosis and provide genetic counseling to reduce the birth of such boys. We report a case of preimplantation genetic diagnosis associated with Duchenne muscular dystrophy. The couple E.P.R., 38-year-old, symptomatic patient heterozygous for a 2 to 47 exon deletion mutation in DMD gene and G.T.S., 39-year-old, sought genetic counseling about preimplantation genetic diagnosis process. They have had a 6-year-old son who died due to Duchenne muscular dystrophy complications. The couple underwent four cycles of intracytoplasmic sperm injection (ICSI) and eight embryos biopsies were analyzed by polymerase chain reaction (PCR) for specific mutation analysis, followed by microarray-based comparative genomic hybridisation (array CGH) for aneuploidy analysis. Preimplantation genetic diagnosis revealed that two embryos had inherited the maternal DMD gene mutation, one embryo had a chromosomal alteration and five embryos were normal. One blastocyst was transferred and resulted in successful pregnancy. The other embryos remain vitrified. We concluded that embryo analysis using associated techniques of PCR and array CGH seems to be safe for embryo selection in cases of X-linked disorders, such as Duchenne muscular dystrophy.
Auszug in der Originalsprache. Bianco B, Christofolini DM, Conceição GS, Barbosa CP. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
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Datensatz: duchenne:28954035
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Gaucher disease is one of the most common lipid-storage disorders, affecting approximately 1 in 75,000 births. Enzyme replacement therapy with recombinant glucocerebrosidase is currently considered the first-line treatment choice for patients with symptomatic Gaucher disease type 1. Oral substrate reduction therapy is generally considered a second-line treatment option for adult patients with mild to moderate Gaucher disease type 1 who are unable or unwilling to receive lifelong intravenous enzyme infusions. The efficacy and safety of the oral substrate reduction therapy miglustat (Zavesca®) in patients with Gaucher disease type 1 have been established in both short-term clinical trials and long-term, open-label extension studies. Published data indicate that miglustat can be used as maintenance therapy in patients with stable Gaucher disease type 1 switched from previous enzyme replacement therapy. We report a case of a 44-year-old Caucasian man with Gaucher disease type 1 who was initially treated with enzyme replacement therapy but, owing to repeated cutaneous allergic reactions, had to be switched to miglustat after several attempts with enzyme replacement therapy. Despite many attempts, desensitization treatment did not result in improved toleration of imiglucerase infusions, and the patient became unwilling to continue with any intravenous enzyme replacement therapy. He subsequently agreed to switch to oral substrate reduction therapy with miglustat 100 mg twice daily titrated up to 100 mg three times daily over a short period. Long-term miglustat treatment maintained both hemoglobin and platelet levels within acceptable ranges over 8 years. The patient's spleen volume decreased, his plasma chitotriosidase levels stayed at reduced levels, and his bone mineral density findings have remained stable throughout follow-up. The patient's quality of life has remained satisfactory. Miglustat showed good gastrointestinal tolerability in this patient, and no adverse eve
Auszug in der Originalsprache. Giuffrida G, Lombardo R, Di Francesco E, Parrinello L, Di Raimondo F, Fiumara A. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
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Datensatz: gaucher:27821156
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
IgA nephropathy (IgAN) is the most common glomerulonephritis, which may also coexist with other diseases. We present two patients with an unusual coincidence of IgAN and Fabry disease (FD). A 26 year-old man underwent a renal biopsy in February 2001. Histopathology showed very advanced IgAN and vascular changes as a result of hypertension. Because of his progressive renal insufficiency the patient began hemodialysis in August 2001. By means of the blood spot test screening method the diagnosis of FD was suspected. Low activity of alpha-galactosidase A in the patient's plasma and leukocytes and DNA analysis confirmed the diagnosis of FD. Enzyme replacement therapy started in July 2004. Then the patient underwent kidney transplantation in November 2005. Currently, his actual serum creatinine level is 250 μmol/l. Other organ damages included hypertrophic cardiomyopathy, neuropathic pain and febrile crisis. After enzyme replacement therapy, myocardial hypertrophy has stabilized and other symptoms have disappeared. No further progression of the disease has been noted.The other patient, a 30 year-old woman, suffered from long-term hematuria with a good renal function. Recently, proteinuria (2.6 g/day) appeared and a renal biopsy was performed. Histopathology showed IgAN with remarkably enlarged podocytes. A combination of IgAN and a high suspicion of FD was diagnosed. Electron microscopy revealed dense deposits in paramesangial areas typical for IgAN and podocytes with inclusive zebra bodies and myelin figures characteristic of FD. FD was confirmed by the decreased alpha-galactosidase A activity in plasma and leukocytes and by DNA and RNA analysis. Enzyme replacement therapy and family screening were initiated. Our results emphasize the role of complexity in the process of diagnostic evaluation of kidney biopsy samples. Electron microscopy represents an integral part of histopathology, and genetic analysis plays a more and more important role in the final diagnosis, which
Auszug in der Originalsprache. Maixnerová D, Tesař V, Ryšavá R, Reiterová J, Poupětová H, Dvořáková L, Goláň L, Neprašová M, Kidorová J, Merta M, Honsová E. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
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Datensatz: fabry:23305247
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba