scholarly journals Hemolytic Uremic Syndrome Due to Methylmalonic Acidemia and Homocystinuria in an Infant: A Case Report and Literature Review

Children ◽  
2021 ◽  
Vol 8 (2) ◽  
pp. 112
Author(s):  
Vasiliki Karava ◽  
Antonia Kondou ◽  
John Dotis ◽  
Georgia Sotiriou ◽  
Spyridon Gerou ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Early Onset ◽  
Renal Damage ◽  
Early Recognition ◽  
Case Reports ◽  
Brain Magnetic Resonance Imaging ◽  
Methylmalonic Acidemia ◽  
Delayed Response ◽  
Homozygous Mutation ◽  
Uremic Syndrome

Methylmalonic acidemia and homocystinuria cobalamin C (cblC) type is the most common inborn error of the intracellular cobalamin metabolism, associated with multisystem involvement and high mortality rates, especially in the early-onset form of the disease. Hemolytic uremic syndrome (HUS) is a rare manifestation and needs to be distinguished from other causes of renal thrombotic microangiopathy. We describe a case of a 3-month-old infant, with failure to thrive, hypotonia and pallor, who developed HUS in the setting of cblC deficit, along with dilated cardiomyopathy, and presented delayed response to optic stimulation in visual evoked potentials, as well as enlarged bilateral subarachnoid spaces and delayed myelination in brain magnetic resonance imaging. Renal damage was reversed, while neurodevelopmental profile and eye contact improved after supplementation with parenteral hydroxycobalamin, oral folic acid, betaine and levocarnitine. Homozygous mutation of c.271dupA in the MMACHC gene was ultimately detected. In this report, we highlight the diagnostic challenges as well as the significance of early recognition and multidisciplinary management of this unusual condition. A brief review of published case reports of early-onset cblC deficit and related HUS is depicted, pointing out the initial clinical presentation, signs of renal damage and outcome, MMACHC gene type of mutations and accompanying extra-renal manifestations.

scholarly journals A Novel Homozygous In-Frame Deletion in Complement Factor 3 Underlies Early-Onset Autosomal Recessive Atypical Hemolytic Uremic Syndrome - Case Report

2021 ◽  
Vol 12 ◽  
Author(s):  
Shirley Pollack ◽  
Israel Eisenstein ◽  
Adi Mory ◽  
Tamar Paperna ◽  
Ayala Ofir ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Exome Sequencing ◽  
Early Onset ◽  
Autosomal Recessive ◽  
Critical Role ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Complement Factor ◽  
Complement Components ◽  
Uremic Syndrome ◽  
Close Relatives

Background and ObjectivesAtypical hemolytic uremic syndrome (aHUS) is mostly attributed to dysregulation of the alternative complement pathway (ACP) secondary to disease-causing variants in complement components or regulatory proteins. Hereditary aHUS due to C3 disruption is rare, usually caused by heterozygous activating mutations in the C3 gene, and transmitted as autosomal dominant traits. We studied the molecular basis of early-onset aHUS, associated with an unusual finding of a novel homozygous activating deletion in C3.Design, Setting, Participants, & MeasurementsA male neonate with eculizumab-responsive fulminant aHUS and C3 hypocomplementemia, and six of his healthy close relatives were investigated. Genetic analysis on genomic DNA was performed by exome sequencing of the patient, followed by targeted Sanger sequencing for variant detection in his close relatives. Complement components analysis using specific immunoassays was performed on frozen plasma samples from the patient and mother.ResultsExome sequencing revealed a novel homozygous variant in exon 26 of C3 (c.3322_3333del, p.Ile1108_Lys1111del), within the highly conserved thioester-containing domain (TED), fully segregating with the familial disease phenotype, as compatible with autosomal recessive inheritance. Complement profiling of the patient showed decreased C3 and FB levels, with elevated levels of the terminal membrane attack complex, while his healthy heterozygous mother showed intermediate levels of C3 consumption.ConclusionsOur findings represent the first description of aHUS secondary to a novel homozygous deletion in C3 with ensuing unbalanced C3 over-activation, highlighting a critical role for the disrupted C3-TED domain in the disease mechanism.

Do not Miss Rare and Treatable Cause of Early-Onset Hemolytic Uremic Syndrome: Cobalamin C Deficiency

Nephron ◽  
2019 ◽  
Vol 142 (3) ◽  
pp. 258-263
Author(s):  
Rezan Topaloglu ◽  
Mihriban İnözü ◽  
Bora Gülhan ◽  
Berrak Gürbüz ◽  
Beril Talim ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Early Onset ◽  
Uremic Syndrome

Eculizumab Modifies Outcomes in Adults with Atypical Hemolytic Uremic Syndrome with Acute Kidney Injury

2018 ◽  
Vol 48 (3) ◽  
pp. 225-233 ◽  
Author(s):  
Mercedes Cao ◽  
Bruna N. Leite ◽  
Tamara Ferreiro ◽  
María Calvo ◽  
Constantino Fernández ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Hemolytic Uremic Syndrome ◽  
Kidney Function ◽  
Case Reports ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Kidney Injury ◽  
Complete Recovery ◽  
Genetic Abnormalities ◽  
Uremic Syndrome ◽  
Meta Analyses

Background: Atypical hemolytic uremic syndrome (aHUS) is a rare disease associated with congenital or acquired genetic abnormalities that result in uncontrolled complement activation, leading to thrombotic microangiopathy and kidney failure. Until recently, the only treatment was plasma exchange or plasma infusion (PE/PI), but 60% of patients died or had permanent kidney damage despite treatment. Eculizumab, a complement inhibitor, has shown promising results in aHUS. However, data are mainly extracted from case reports or studies of heterogeneous cohorts, and no direct comparison with PE/PI is available. Methods: An observational retrospective study of adult, dialysis-dependent aHUS patients with acute kidney injury (AKI) who were treated with either PE/PI alone or with second-line eculizumab in our center. We compared the effect of PE/PI and eculizumab on kidney function, hypertension, proteinuria, hematologic values, relapse, and death. Results: Thirty-one patients were included (females, 18; sporadic aHUS, 29; mean age, 46 ± 20 years). Twenty-six patients were treated with PE/PI alone, and 5 were deemed to be plasma-resistant and received eculizumab after stopping PE/PI. Among patients receiving eculizumab, 80% attained complete recovery of kidney function, 100% stopped dialysis, 20% had decreased proteinuria, and no patient relapsed (vs. 38.5, 50, 15.4, and 11.5%, respectively, of patients receiving only PE/PI). At 1-year of follow-up, no deaths had occurred in either group. Conclusion: Eculizumab shows greater efficacy than PE/PI alone for the treatment of adult aHUS patients with AKI. Prospective studies and meta-analyses are warranted to confirm our findings and set guidelines for treatment, monitoring, and maintenance.

scholarly journals Chemokine Receptor CCR1 Disruption Limits Renal Damage in a Murine Model of Hemolytic Uremic Syndrome

2012 ◽  
Vol 180 (3) ◽  
pp. 1040-1048 ◽  
Author(s):  
Maria V. Ramos ◽  
Constance Auvynet ◽  
Lucie Poupel ◽  
Mathieu Rodero ◽  
Maria Pilar Mejias ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Chemokine Receptor ◽  
Murine Model ◽  
Renal Damage ◽  
Uremic Syndrome

scholarly journals Absence of interleukin-10 reduces progression of shiga toxin-induced hemolytic uremic syndrome

2021 ◽  
Vol 135 (3) ◽  
pp. 575-588
Author(s):  
Gonzalo Ezequiel Pineda ◽  
Bárbara Rearte ◽  
María Florencia Todero ◽  
Andrea Cecilia Bruballa ◽  
Alan Mauro Bernal ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Shiga Toxin ◽  
Renal Damage ◽  
Polymorphonuclear Neutrophils ◽  
Enzyme Linked Immunosorbent Assay ◽  
Plasma Urea ◽  
Tnf Α ◽  
Uremic Syndrome ◽  
Anti Inflammatory

Abstract Hemolytic Uremic Syndrome (HUS), a disease triggered by Shiga toxin (Stx), is characterized by hemolytic anemia, thrombocytopenia and renal failure. The inflammatory response mediated by polymorphonuclear neutrophils (PMNs) and monocytes is essential to HUS onset. Still, the role of anti-inflammatory cytokines is less clear. The deficiency of IL-10, an anti-inflammatory cytokine, leads to severe pathology in bacterial infections but also to beneficial effects in models of sterile injury. The aim of this work was to analyze the role of IL-10 during HUS. Control and IL-10 lacking mice (IL-10−/−) were intravenously injected with Stx type 2 (Stx2) and survival rate was evaluated. PMN and circulating and renal pro- and anti-inflammatory factors were analyzed by FACS and enzyme-linked immunosorbent assay (ELISA) respectively. IL-10−/− mice showed a higher survival associated with lower renal damage reflected by reduced plasma urea and creatinine levels than control mice. Circulating PMN increased at 72 h in both mouse strains accompanied by an up-regulation of CD11b in control mice. In parallel, renal PMN were significantly increased only in control mice after toxin. Plasma TNF-α, IL-6 and corticosterone levels were higher increased in IL-10−/− than control mice. Simultaneously renal TNF-α raised constantly but was accompanied by increased TGF-β levels in IL-10−/− mice. These results demonstrate that the profile of circulating and renal cytokines after Stx2 differed between strains suggesting that balance of these factors could participate in renal protection. We conclude that IL-10 absence has a protective role in an experimental model of HUS by reducing PMN recruitment into kidney and renal damage, and increasing mice survival.

Severe deficiency of plasma factor H is associated with early-onset atypical hemolytic uremic syndrome

2018 ◽  
Vol 102 ◽  
pp. 232-233
Author(s):  
Yuzhou Zhang ◽  
Jeffrey Saland ◽  
Sarah Roberts ◽  
Gabriella Pitcher ◽  
Nicolo Borsa ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Early Onset ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Factor H ◽  
Severe Deficiency ◽  
Plasma Factor ◽  
Uremic Syndrome

Gemcitabine-induced hemolytic-uremic syndrome treated with eculizumab or plasmapheresis: two case reports

2017 ◽  
Vol 87 (02) ◽  
pp. 100-106 ◽  
Author(s):  
María Esperanza López Rubio ◽  
Raquel Rodado Martínez ◽  
María Luisa Illescas ◽  
Encarnación Mateo Bosch ◽  
Mercedes Martínez Díaz ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Case Reports ◽  
Uremic Syndrome

scholarly journals POS-418 HOMOZYGOUS MUTATION IN COMPLEMENT C3 GENE ASSOCIATED WITH FAMILIAL HEMOLYTIC UREMIC SYNDROME: CASE SERIES

2021 ◽  
Vol 6 (4) ◽  
pp. S180
Author(s):  
S. ALZAHRANI ◽  
A. Aldajani ◽  
M. Ahmed A. ◽  
A. Alghamdi ◽  
N. Abdulmajeed ◽  
...  
Keyword(s):  
Hemolytic Uremic Syndrome ◽  
Case Series ◽  
Complement C3 ◽  
Homozygous Mutation ◽  
Uremic Syndrome ◽  
C3 Gene ◽  
Familial Hemolytic Uremic Syndrome

scholarly journals Case series: coronavirus disease 2019 infection as a precipitant of atypical hemolytic uremic syndrome: two case reports

2021 ◽  
Vol 15 (1) ◽  
Author(s):  
Christine J. Kurian ◽  
Zachary French ◽  
Patrick Kukulich ◽  
Matthew Lankiewicz ◽  
Sushil Ghimire ◽  
...  
Keyword(s):  
Renal Failure ◽  
Hemolytic Uremic Syndrome ◽  
Thrombotic Microangiopathy ◽  
Influenza A ◽  
Case Reports ◽  
Atypical Hemolytic Uremic Syndrome ◽  
Case Series ◽  
Oliguric Renal Failure ◽  
History Of ◽  
Uremic Syndrome

Abstract Background Atypical hemolytic uremic syndrome is an exceedingly rare thrombotic microangiopathy caused by accelerated activation of the alternative complement pathway. Case presentation Here, we report two cases of patients presenting with suspected atypical hemolytic uremic syndrome precipitated by coronavirus disease 2019 infection. The first patient, a 25-year-old Hispanic male, had one prior episode of thrombotic microangiopathy presumed to be atypical hemolytic uremic syndrome precipitated by influenza A, and re-presented with thrombocytopenia, microangiopathic hemolytic anemia, nonoliguric renal failure, and normal ADAMTS13 activity, with confirmed coronavirus disease 2019 positivity. The second patient, a 31-year-old Caucasian female, had no personal history of thrombotic microangiopathy, though reported a family history of suspected atypical hemolytic uremic syndrome. She presented with similar laboratory derangements, oliguric renal failure requiring hemodialysis, and confirmed coronavirus disease 2019 positivity. Both patients were treated with eculizumab with complete resolution of their hematologic and renal complications. Conclusion To our knowledge, this represents the largest case series of atypical hemolytic uremic syndrome precipitated by coronavirus disease 2019 in adults.

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