scholarly journals Fabry Nephropathy

2017 ◽  
Vol 141 (8) ◽  
pp. 1127-1131 ◽  
Author(s):  
Prudence Colpart ◽  
Sophie Félix
Keyword(s):  
Clinical Signs ◽  
Lysosomal Storage ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Disease Evolution ◽  
Enzyme Replacement ◽  
Life Threatening ◽  
A Cell ◽  
Gla Gene ◽  
Fabry Nephropathy

Fabry disease is a rare X-linked recessive lysosomal storage disease. Multiple mutations of the GLA gene lead to a deficient or absent activity of the lysosomal enzyme α-galactosidase A, resulting in progressive glycotriaosylceramide accumulation in many organs. Low α-galactosidase A activity and mutations in the GLA gene confirm the diagnosis. Clinical signs are multisystemic, heterogeneous, and progressive. Renal, cardiac, and neurovascular involvements are the main life-threatening complications, highlighting the importance of an early initiation of enzyme replacement therapy improving long-term outcome. Fabry nephropathy lesions are characterized by a cell vacuolization of glomeruli, tubules, interstitium, and arteries and by ultrastructural myelin bodies. The main histologic differential diagnoses are toxicity of lysosomal inhibitors and other renal lipidoses. Renal biopsies are not necessary for diagnosis but have an important role in the evaluation of disease evolution and treatment efficiency, which is a major challenge for improving outcome and quality of life.

Enfermedad de Fabry y enfermedad renal terminal: importancia de la combinación del trasplante renal y la terapia de reemplazo enzimático

2019 ◽  
Vol 1 (1) ◽  
pp. 21-27
Author(s):  
​Luis F. Pineda Galindo ◽  
Leslie Moranchel García
Keyword(s):  
Kidney Transplant ◽  
Kidney Diseases ◽  
Lysosomal Storage ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Enzyme Replacement ◽  
Multiple Organs ◽  
Glomerular Filtration Rate Decline ◽  
Stage Renal Disease ◽  
End Stage

Introduction. Fabry disease (FD) is a lysosomal storage disease with an X-linked inheritance caused by an enzyme deficiency leading to tissue accumulation of globotriaosylceramide–GL-3, cellular dysfunction, and tissue inflammation, which will end in progressive damage to multiple organs if untreated. Symptomatology is multi-systemic. In advanced disease, kidney, heart and central nervous system are susceptible to such accumulation and are usually responsible for fatal outcomes. Cases presentation. Two FD cases treated with enzyme replacement therapy (ERT) shortly before receiving a cadaveric kidney transplant are presented. FD therapy is multidisciplinary, requires a symptomatic approach and ERT, targeted to substrate accumulation. ERT is beneficial for organ function and patients’ survival. ERT enables GL-3 clearance from different kidney cell lines, stabilization in glomerular filtration rate decline, and reduction of catastrophic kidney complications. After kidney transplantation, graft survival is similar to or better than transplant for other kidney diseases. Conclusions. A complete treatment must include kidney transplant and ERT. Our cases results confirm the beneficial effect of ERT in patients who underwent renal transplantation for FD-related end-stage renal disease (ESRD). When these patients with minimal disease burden in other organs timely receive a kidney transplant, their potential for a positive long-term outcome is evident.

Hallazgos oftalmológicos en enfermedad de Fabry: relación de su severidad en una familia mexicana

2019 ◽  
Vol 1 (1) ◽  
pp. 43-49
Author(s):  
Araceli Borja Borja ◽  
Gabriela Salas Pérez ◽  
Pablo Radillo Díaz
Keyword(s):  
Premature Mortality ◽  
Retinal Vessel ◽  
Multiple Organ ◽  
High Morbidity ◽  
Lysosomal Storage ◽  
Enzyme Replacement ◽  
Non Invasive ◽  
High Incidence ◽  
Cornea Verticillata ◽  
Gla Gene

Introduction. Fabry disease (FD) is a lysosomal storage disorder associated with multiple organ dysfunction which eventually leads to high morbidity and premature mortality. Ophthalmologic findings in FD are very common and have been described extensively. We describe the ophthalmologic findings of a family diagnosed with FD at Hospital de Especialidades de Puebla and establish their relationship with other phenotypic findings. Cases Presentation. A renal, cardiac, audiological, neurological, and ophthalmologic evaluation was carried out. The disease was confirmed by GLA gene sequencing. The ophthalmologic assessment was focused on the changes described in the literature, as well as the search for other anomalies possibly related to the disease. All the patients had the c.260delA (P.Glu87Glyfs*34) mutation in the GLA gene. The main ophthalmologic finding in our patients was cornea verticillata (in 100 % of the female patients). Other ophthalmologic manifestations were dry eye, retinal vessel tortuosity, ametropia, chromatic vision disorders, ocular annexes, eyelids, and conjuntiva disorders. Conclusions. Most of the assessed patients showed ophthalmologic changes, consistent with the results described in the literature. A remarkable finding in the sample was the high incidence of changes in women, in whom one would not expect the disease to be as severe because they are heterozygous. Ophthalmologic abnormalities in FD require deeper evaluation to establish their possible use as markers of disease progression and/or enzyme replacement therapy initiation due to the benefit of the non-invasive nature of ophthalmologic evaluations.

The management of Hemorrhoidal Disease by Dearterialization and Mucopexy.

2020 ◽  
Vol 15 ◽  
Author(s):  
Veronica De Simone ◽  
Francesco Litta ◽  
Angelo Parello ◽  
Paola Campennì ◽  
Raffaele Orefice ◽  
...  
Keyword(s):  
Postoperative Management ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Doppler Probe ◽  
Minimally Invasive Surgical ◽  
Bowel Movements ◽  
Excessive Strain ◽  
Life Threatening ◽  
Hemorrhoidal Prolapse ◽  
The Impact

: Several minimally invasive surgical procedures have been recently developed to treat hemorrhoids without any excision. About 25 years ago, a non-excisional procedure providing doppler-guided ligation of the hemorrhoidal arteries has been proposed - named “hemorrhoidal dearterialization”. The original technique has been modified over the years, and indications were expanded. In particular, a plication of the redundant and prolapsing mucosa/submucosa of the rectum (named “mucopexy”) has been introduced to treat hemorrhoidal prolapse, without excision of the hemorrhoidal piles. At present, the THD® Doppler procedure is one of the most used techniques to treat hemorrhoids. Aim of this technique is to realize a target dearterialization, using a Doppler probe with the final purpose to reduce the arterial overflow to the hemorrhoidal piles. In case of associated hemorrhoidal prolapse, a mucopexy is performed together with Doppler-guided dearterialization. The entity and circumferential extension of the hemorrhoidal prolapse guides the mucopexy, which can be considered tailored to a single patient; the dearterialization should be considered mandatory. Advantages of this surgical technique are the absence of serious and life-threatening postoperative events, chronic complications, and limited recurrence risks. The impact of the procedure on the anorectal physiology is negligible. However, a careful postoperative management is mandatory to avoid complications and to guarantee an improved long-term outcome. Therefore, regular physiologic bowel movements, excessive strain at the defecation and strong physical activity are advisable.

scholarly journals Characterization and phosphoproteomic analysis of a human immortalized podocyte model of Fabry disease generated using CRISPR/Cas9 technology

2016 ◽  
Vol 311 (5) ◽  
pp. F1015-F1024 ◽  
Author(s):  
Ester M. Pereira ◽  
Anatália Labilloy ◽  
Megan L. Eshbach ◽  
Ankita Roy ◽  
Arohan R. Subramanya ◽  
...  
Keyword(s):  
Fabry Disease ◽  
Human Kidney ◽  
Premature Death ◽  
Antibody Array ◽  
Cell Models ◽  
Lysosomal Storage ◽  
Protein Levels ◽  
Gla Gene ◽  
Fabry Nephropathy ◽  
And Control

Fabry nephropathy is a major cause of morbidity and premature death in patients with Fabry disease (FD), a rare X-linked lysosomal storage disorder. Gb3, the main substrate of α-galactosidase A (α-Gal A), progressively accumulates within cells in a variety of tissues. Establishment of cell models has been useful as a tool for testing hypotheses of disease pathogenesis. We applied CRISPR/Cas9 genome editing technology to the GLA gene to develop human kidney cell models of FD in human immortalized podocytes, which are the main affected renal cell type. Our podocytes lack detectable α-Gal A activity and have increased levels of Gb3. To explore different pathways that could have distinct patterns of activation under conditions of α-gal A deficiency, we used a high-throughput antibody array to perform phosphorylation profiling of CRISPR/Cas9-edited and control podocytes. Changes in both total protein levels and in phosphorylation status per site were observed. Analysis of our candidate proteins suggests that multiple signaling pathways are impaired in FD.

scholarly journals Study of hypoglycemia in neonates with low birth weight

2020 ◽  
Vol 7 (8) ◽  
pp. 409-413
Author(s):  
Dr. Ekta Acharya ◽  
Keyword(s):  
Birth Weight ◽  
Low Birth Weight ◽  
Clinical Signs ◽  
Time Interval ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Low Birth Weight Babies ◽  
Short And Long Term ◽  
Heel Prick ◽  
Glycogen Stores

Background and Aim: The maintenance of normoglycemia in newborns depends upon theadequacy of glycogen stores, maturation of glycogenolytic and gluconeogenic pathways, andintegrated endocrine response. The current study, therefore, proposes to observe the clinical profileof low-birth-weight babies concerning the occurrence of hypoglycemia. Materials and Methods:The neonates with a weight of fewer than 2500 grams were included in the study. A total of 100infants were included in the study. They were divided into two groups with infants withhypoglycemia in one group and infants with normoglycemic in another group. The aseptic conditionwas maintained and with the help of heel prick, the capillary blood was collected. The capillary bloodwas screened with the help of reagent strips. Results: Out of the total 100 neonates, a total of 76neonates were normoglycemic and 24 neonates had hypoglycaemic episodes. Overall 22 episodes ofhypoglycemia were recorded. There was no significant association between birth weight andepisodes of hypoglycemia. The majority of hypoglycaemic infants were male. Conclusion:Hypoglycemia associated with abnormal clinical signs (symptomatic hypoglycemia) has a poor short-and long-term outcome but evidence of risk in the absence of clinical signs (asymptomatichypoglycemia) is inconclusive. Small for gestational age is a significant determinant forhypoglycemia. Hypoglycaemic episodes were significantly noticed in the first 24 hours as comparedto another time interval.

scholarly journals Anderson–Fabry Disease: From Endothelial Dysfunction to Emerging Therapies

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Cosimo A. Stamerra ◽  
Rita Del Pinto ◽  
Paolo di Giosia ◽  
Claudio Ferri ◽  
Amirhossein Sahebkar
Keyword(s):  
Fabry Disease ◽  
Organ Damage ◽  
Lysosomal Storage ◽  
Messenger Ribonucleic Acid ◽  
Gene Therapies ◽  
Enzyme Replacement ◽  
Emerging Therapies ◽  
Life Threatening ◽  
Molecular Aspects ◽  
Partial Deficiency

The Anderson–Fabry disease is a rare, X-linked, multisystemic, progressive lysosomal storage disease caused by α-galactosidase A total or partial deficiency. The resulting syndrome is mainly characterized by early-onset autonomic neuropathy and life-threatening multiorgan involvement, including renal insufficiency, heart disease, and early stroke. The enzyme deficiency leads to tissue accumulation of the glycosphingolipid globotriaosylceramide and its analogues, but the mechanisms linking such accumulation to organ damage are only partially understood. In contrast, enzyme replacement and chaperone therapies are already fully available to patients and allow substantial amelioration of quality and quantity of life. Substrate reduction, messenger ribonucleic acid (mRNA)-based, and gene therapies are also on the horizon. In this review, the clinical scenario and molecular aspects of Anderson–Fabry disease are described, along with updates on disease mechanisms and emerging therapies.

Clinical characteristics and long-term outcome of lung lobe torsions in cats: a review of 10 cases (2000–2021)

2021 ◽  
pp. 1098612X2110548
Author(s):  
Catherine Tindale ◽  
Filippo Cinti ◽  
Matteo Cantatore ◽  
Alistair Freeman ◽  
Leonardo Cavaliere ◽  
...  
Keyword(s):  
Intraoperative Complications ◽  
Clinical Signs ◽  
Case Series ◽  
The Other ◽  
Complication Rates ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Lung Lobe ◽  
Lung Lobes

Case series summary Lung lobe torsion is rare in cats. The aim of this multi-institution retrospective study was to describe clinical and diagnostic findings, treatments and outcomes of lung lobe torsion (LLT) in 10 cats. Dyspnoea and tachypnoea were the most common clinical signs. Pleural effusion was present in nine cats at presentation. Fluid analysis confirmed chylothorax in three cats. Nine cats underwent CT and five cats had thoracic radiographs taken. A diagnosis was made preoperatively in six cats, while in the other four cats it was made at exploratory thoracotomy. Affected lung lobes were the right cranial (n = 4/11), left cranial (n = 4/11) and right middle (n = 3/11). One cat had a concurrent torsion of two lung lobes. Lung lobectomy was successfully performed in all cases. Based on clinical, diagnostic and lung histopathology findings, three cats had idiopathic and seven cats secondary LLT. Intraoperative complications included hypotension and hypothermia in four and five cats, respectively. Postoperative complications occurred in six cats and lead to euthanasia or death in four cats, whereas complications resolved in the other two cats. Three cats were euthanased within 5 weeks of discharge. For the three cats surviving long term, including one euthanased at 252 days postoperatively, owner-described outcomes and quality of life were considered good to excellent. Relevance and novel information Secondary LLT associated with underlying thoracic pathology was associated with high complication rates and poor outcomes. Long-term outcomes of cats undergoing surgery for LLT and surviving the perioperative period were deemed good to excellent.

scholarly journals Space-occupying cerebellar infarction: complications, treatment, and outcome

2013 ◽  
Vol 34 (5) ◽  
pp. E8 ◽  
Author(s):  
Hermann Neugebauer ◽  
Jens Witsch ◽  
Klaus Zweckberger ◽  
Eric Jüttler
Keyword(s):  
Treatment Strategies ◽  
Cerebellar Infarction ◽  
General Belief ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Cerebellar Stroke ◽  
Brainstem Compression ◽  
Pressure Lowering ◽  
Life Threatening ◽  
Close Cooperation

Space-occupying brain edema is a frequent and one of the most dreaded complications in ischemic cerebellar stroke. Because the tight posterior fossa provides little compensating space, any space-occupying lesion can lead to life-threatening complications through brainstem compression or compression of the fourth ventricle and subsequent hydrocephalus, both of which may portend transtentorial/transforaminal herniation. Patients with large cerebellar infarcts should be treated and monitored very early on in an experienced stroke unit or (neuro)intensive care unit. The general treatment of ischemic cerebellar infarction does not differ from that of supratentorial ischemic strokes. Treatment strategies for space-occupying edema include pharmacological antiedema and intracranial pressure–lowering therapies, ventricular drainage by means of an extraventricular drain, and suboccipital decompressive surgery, with or without resection of necrotic tissue. Timely escalation of treatment is crucial and should be guided by clinical and neuroradiological rationales. Patients in a coma after hydrocephalus and/or local brainstem compression may also benefit from more aggressive surgical treatment, as long as the conditions are reversible. Contrary to the general belief that outcome in survivors of space-occupying cerebellar stroke is usually good, recent studies suggest that for many of these patients, the long-term outcome is not good. In particular, advanced age and additional brainstem infarction seem to be predictors for poor outcome. Further trials are necessary to investigate these findings systematically and provide better selection criteria to help guide decisions about surgical therapies, which should always be carried out in close cooperation among neurointensive care physicians, neurologists, and neurosurgeons.

scholarly journals Newborn Screening of Lysosomal Storage Disorders

2010 ◽  
Vol 56 (7) ◽  
pp. 1071-1079 ◽  
Author(s):  
Deborah Marsden ◽  
Harvey Levy
Keyword(s):  
Newborn Screening ◽  
Screening Method ◽  
Lysosomal Storage Disorders ◽  
Krabbe Disease ◽  
Lysosomal Storage ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Mucopolysaccharidosis I ◽  
Technological Advances ◽  
Storage Disorders

Abstract Background: Newborn screening is a state-based public health program established as a means for the early detection and treatment of certain medical conditions to minimize developmental disability and mortality. The program was initiated more than 40 years ago to detect and prevent phenylketonuria. Recent technological advances have expanded the scope of newborn screening to include more than 30 inborn errors of metabolism. Consideration is now being given to inclusion of screening for lysosomal storage disorders (LSDs). Content: Some lysosomal storage disorders (LSDs) express early in infancy or childhood and are treatable. Initiation of treatment in presymptomatic patients or in syptomatic patients before important symptoms are present may improve the long-term outcome. Therefore, early diagnosis is critical. Based on the availability of therapy and development of a screening method, 6 of the more than 40 known LSDs are candidates for newborn screening in the US: Gaucher disease, Pompe disease, Fabry disease, Niemann-Pick disease, mucopolysaccharidosis I, and Krabbe disease. This report reviews the history of newborn screening, the technology that has allowed for expanded screening during the last decade, LSDs and their treatment, and the evolving methods that might allow additional expansion of newborn screening to include certain LSDs. Summary: Recent and evolving technological advances may be implemented for newborn screening for LSDs. This screening will identify presymptomatic newborns, allowing for early treatment and prevention or limitation of morbidity otherwise associated with these inherited rare diseases.

Short- and Long-Term Outcome of Dogs Following Surgical Correction of a Persistent Right Aortic Arch

2014 ◽  
Vol 50 (3) ◽  
pp. 181-186 ◽  
Author(s):  
Ingar A. Krebs ◽  
Shauna Lindsley ◽  
Stephanie Shaver ◽  
Catriona MacPhail
Keyword(s):  
Aortic Arch ◽  
Clinical Signs ◽  
Right Aortic Arch ◽  
Surgical Correction ◽  
Term Outcome ◽  
Long Term Outcome ◽  
And Gender ◽  
Owner Satisfaction ◽  
Time Of Presentation

This study reports the survival to discharge, postdischarge survival, and long-term outcome of dogs following surgical correction of a persistent right aortic arch (PRAA). Information for 52 dogs, 28 dogs, and 23 dogs was available for analysis of survival to discharge, postdischarge survival, and long-term outcome, respectively. Ninety-two percent of dogs survived to the time of discharge and 18% of dogs surviving to discharge were euthanized within 2 mo of surgery. Breed, age at the time of presentation, and gender were not correlated with increased odds of death prior to discharge from the hospital. Long-term outcome for dogs was excellent in 30%, good in 57%, and poor in 13% of dogs. Although this study shows a relatively high mortality rate prior to discharge from the hospital and within 2 mo of surgical treatment, the long-term outcome is good or excellent in 87% of survivors. Dogs frequently display either residual clinical signs or require dietary modification long-term, but owner satisfaction is high.

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