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Datensatz: gaucher:459598
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FindZebra
Datensatz: gaucher:459598
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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Datensatz: fabry:9375832
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.
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Datensatz: duchenne:29843823
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.
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Datensatz: hae:34656181
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: fabry:6775671
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: fac:26251157
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: hae:26939307
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: duchenne:10529540
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: hae:17890276
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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FindZebra
Datensatz: fabry:32042454
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Fabry's disease, an X linked recessive disorder caused by the deficiency of alpha-galactosidase A (alpha-gal A), leads to progressive accumulation of glycosphingolipids. We report this rare disease in a 19-year-old boy who presented with angiokeratomas, paresthesia and corneal opacities, and nerve biopsy revealed by electron microscopy lamellated inclusions in the smooth muscle, perineurial and endothelial cells characteristic of Fabry's disease.
Auszug in der Originalsprache. Gayathri N, Yasha TC, Kanjalkar M, Agarwal S, Sagar BK, Santosh V, Shankar SK. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: fabry:19893666
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Familial amyloidotic polyneuropathy (FAN type 1) is a rare systemic disease that causes severe and disabling peripheral neuropathy. We describe the phenotypic, radiological, and pathological characteristics of a patient with familial amyloid polyneuropathy type 1 who had evidence of motor-sensory-autonomic neuropathy, ocular vitreous deposits, diffuse leptomeningeal involvement, and hypertrophic cardiomyopathy. Muscle involvement, an infrequently reported feature, was also observed. Early recognition of the disease has significant therapeutic implications.
Auszug in der Originalsprache. Prashantha DK, Taly AB, Sinha S, Yasha TC, Gayathri N, Kovur JM, Vijayan J. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: fac:20814501
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Fabry disease (FD) is an X-linked lysosomal storage disorder due to deficient alpha-galactosidase activity leading to intracellular glycosphingolipid accumulation. Multiple variants have been reported in the GLA gene coding for alpha-galactosidase, and the question of the pathogenicity of rare variants needs to be addressed, especially in patients with mild phenotypes. The patient, a 37-year-old female, presented with a persistent proteinuria after an otherwise uncomplicated first pregnancy. Renal biopsy showed both mild mesangial IgA deposits, and a striking vacuolization of podocytes and tubular cells consistent with Fabry disease. On electron microscopy, discrete but characteristic pseudo-myelinic lamellar inclusions were observed in the podocytes' lysosomes. A more detailed physical examination revealed an angiokeratoma, and medical history ancient acroparesthesia. There was no cardiac or cerebral involvement of Fabry disease on magnetic resonance imaging. While blood enzymatic activity of alpha-ga lactosidase was normal in this patient, lysoGb3 was elevated (3 N), and a rare heterozygous variant called c.610 T > C was documented in GLA gene. The patient was treated with an ACE inhibitor, with a rapid decrease in proteinuria. After a 5-year follow-up, her renal function has remained normal, with mild proteinuria, and normal cardiac echography. We report and phenotypically describe the first case of a Fabry disease female patient carrying the GLA c.610 T > C variant associated with a renal-predominant clinical presentation.
Auszug in der Originalsprache. Greillier S, Daniel L, Caillaud C, Dussol B, Touchard G, Goujon JM, Jourde-Chiche N, Bobot M. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
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Datensatz: fabry:32590976
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Genetic changes in the LIM homeobox transcription factor 1 beta (LMX1B) have been associated with focal segmental glomerulosclerosis (FSGS) without the extra-renal or ultrastructural manifestations of Nail-patella syndrome (NPS) known as Nail-patella-like renal disease (NPLRD). Fabry disease (FD) is an X-linked lysosomal disease caused by the deficiency of alpha-galactosidase A. The classic form of the disease is characterized by acroparesthesia, angiokeratomas, cornea verticillata, hypertrophic cardiomyopathy, strokes, and chronic kidney disease. Podocyte myelin bodies on ultrastructural examination of kidney tissue are very characteristic of FD; however some medications and other conditions may mimic this finding. Here, we report on a female patient with chronic kidney disease (CKD), positive family history for kidney disease and kidney biopsy showing a FSGS lesion and presence of focal myelin figures within podocytes concerning for FD. However, genetic testing for FD was negative. After comprehensive clinical, biochemical, and genetic evaluation, including whole exome and RNA sequencing, she was ultimately diagnosed with NPLRD. This case illustrates the difficulties of diagnosing atypical forms of rare Mendelian kidney diseases and the role of a multidisciplinary team in an individualized medicine clinic setting in combination with state-of-the-art sequencing technologies to reach a definitive diagnosis.
Auszug in der Originalsprache. Pinto E Vairo F, Pichurin PN, Fervenza FC, Nasr SH, Mills K, Schmitz CT, Klee EW, Herrmann SM. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
FindZebra
Datensatz: fabry:32791958
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
Fabry disease (FD) has an extensive phenotypic expression associated with GLA gene variants. The GLA gene variant c.352C>T/p.Arg118Cys was considered with uncertain pathogenicity because of the finding of high residual alpha-galactosidase A (α-Gal A) enzyme activity, the absence of Mendelian segregation with an FD phenotype with many individuals remaining asymptomatic at old ages and the lack of globotriaosylceramide (Gb3) deposits in tissues. Gb3 deposits are found in kidneys before the progression to overt microalbuminuria and decreased glomerular filtration. We describe a family with c.352C>T/p.Arg118Cys variant and pathognomonic signs of FD renal damage in masculine children. The proband died of end-stage renal failure and we analyzed GLA gene in his offspring and found the variant in all daughters and five of seven grandchildren. In patients who we measure plasma and urinary Gb3, α-Gal A enzyme activity, and plasma globotriaosylsphingosine (Lyso-Gb3), these were normal or almost normal. A kidney biopsy was performed in two boys and one girl with normal renal function and characteristic signs of FD as enlarged and vacuolated epithelial cells, myelin figures, myelin-like figures, lamellated structures in podocytes and endothelial cells, were found in boys. These boys received agalsidase beta 1 mg/kg IV infusion every other week to prevent further renal damage. This is the first report that shows a link between FD renal Gb3 deposits and c.352C>T/p.Arg118Cys variant, supporting pathogenicity of a variant considered until now with uncertain pathogenicity.
Auszug in der Originalsprache. Cerón-Rodríguez M, Ramón-García G, Barajas-Colón E, Franco-Álvarez I, Salgado-Loza JL. · Lizenz: cc by. Für den vollständigen Kontext die Originalpublikation öffnen.
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Datensatz: fabry:31566927
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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Datensatz: fabry:18507557
Quellenstand: f262dbc3a1d234f500d9173f9ebf8d19996b03ba
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Datensatz: gaucher:304070
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