2,336 results match your criteria Homocystinuria


Absence of MMACHC in peripheral retinal cells does not lead to an ocular phenotype in mice.

Biochim Biophys Acta Mol Basis Dis 2021 Jun 17:166201. Epub 2021 Jun 17.

Division of Metabolism and Children's Research Center, University Children's Hospital Zürich, University of Zürich, Switzerland. Electronic address:

Combined methylmalonic aciduria with homocystinuria (cblC type) is a rare disease caused by mutations in the MMACHC gene. MMACHC encodes an enzyme crucial for intracellular vitamin B metabolism, leading to the accumulation of toxic metabolites e.g. Read More

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Inborn Errors of Metabolism Associated With Autism Spectrum Disorders: Approaches to Intervention.

Front Neurosci 2021 28;15:673600. Epub 2021 May 28.

Department of Paediatrics, University Hospital Center Zagreb and University of Zagreb School of Medicine, Zagreb, Croatia.

Increasing evidence suggests that the autism spectrum disorder (ASD) may be associated with inborn errors of metabolism, such as disorders of amino acid metabolism and transport [phenylketonuria, homocystinuria, S-adenosylhomocysteine hydrolase deficiency, branched-chain α-keto acid dehydrogenase kinase deficiency, urea cycle disorders (UCD), Hartnup disease], organic acidurias (propionic aciduria, L-2 hydroxyglutaric aciduria), cholesterol biosynthesis defects (Smith-Lemli-Opitz syndrome), mitochondrial disorders (mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes-MELAS syndrome), neurotransmitter disorders (succinic semialdehyde dehydrogenase deficiency), disorders of purine metabolism [adenylosuccinate lyase (ADSL) deficiency, Lesch-Nyhan syndrome], cerebral creatine deficiency syndromes (CCDSs), disorders of folate transport and metabolism (cerebral folate deficiency, methylenetetrahydrofolate reductase deficiency), lysosomal storage disorders [Sanfilippo syndrome, neuronal ceroid lipofuscinoses (NCL), Niemann-Pick disease type C], cerebrotendinous xanthomatosis (CTX), disorders of copper metabolism (Wilson disease), disorders of haem biosynthesis [acute intermittent porphyria (AIP)] and brain iron accumulation diseases. In this review, we briefly describe etiology, clinical presentation, and therapeutic principles, if they exist, for these conditions. Additionally, we suggest the primary and elective laboratory work-up for their successful early diagnosis. Read More

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Report of rapid diagnosis and precise management of related intracellular cobalamin defect.

BMJ Case Rep 2021 Jun 3;14(6). Epub 2021 Jun 3.

Medical Genetics, Kasturba Medical College Manipal, Manipal, Karnataka, India

Disorders of intracellular cobalamin metabolism are a group of metabolic disorders that lead to varied clinical presentation from intrauterine life to adulthood. We report a male infant with developmental regression, macrocytic anaemia and hyperpigmentation. Exome sequencing identified a homozygous pathogenic variant in the gene, known to cause homocystinuria, cblD type (MIM #277410). Read More

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Unilateral and Spontaneous Complete Anterior Dislocation of the Crystalline Lens in a Patient With Homocystinuria.

Cureus 2021 Apr 23;13(4):e14655. Epub 2021 Apr 23.

Department of Ophthalmology, Eye Research Center, The Five Senses Institute, Rassoul Akram Hospital, Iran University of Medical Sciences, Tehran, IRN.

Homocystinuria is a metabolic disorder caused by a deficiency of cystathionine beta-synthase with autosomal recessive inheritance. Clinically it is characterized by lens subluxation, skeletal abnormalities, and thromboembolic accidents. We present a 6-year-old boy who was a known case of homocystinuria. Read More

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[New Inborn Errors of Metabolism added in the French program of neonatal screening].

Med Sci (Paris) 2021 May 18;37(5):507-518. Epub 2021 May 18.

Infinity, Inserm UMR1291, CNRS UMR5051, Université de Toulouse III, 31000 Toulouse, France. - Centre régional de dépistage néonatal, Institut fédératif de biologie, Groupe hospitalier Purpan, 330 avenue de Grande-Bretagne, 31059 Toulouse Cedex 9, France.

Inborn Errors of Metabolism (IEM) are rare and heterogenous disorders. For most IEMs, clinical signs are non-specific or belated. Late diagnosis is frequent, leading to death or severe sequelae. Read More

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Recurrent dislocation of binocular crystal lenses in a patient with cystathionine beta-synthase deficiency.

BMC Ophthalmol 2021 May 13;21(1):212. Epub 2021 May 13.

SUNY College of Optometry, New York, NY, USA.

Background: Ectopia lentis is the common ocular manifestation of homocystinuria resulting from cystathionine beta-synthase (CBS) deficiency which has a high risk of thromboembolic complications.

Case Presentation: The present study reports the case of a teenager with recurrent lens dislocation and glaucoma. He was diagnosed with CBS deficiency according to a high level of serum homocysteine and compound heterozygous mutations at two different positions on the CBS gene. Read More

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Epimutation of MMACHC compound to a genetic mutation in cblC cases.

Mol Genet Genomic Med 2021 May 12:e1625. Epub 2021 May 12.

Department of Pediatric Endocrinology and Genetic Metabolism, Children's Hospital Affiliated to Zhengzhou University, Henan Children's Hospital, Zhengzhou Children's Hospital, Zhengzhou, China.

Background: Methylmalonic aciduria (MMA) combined with homocystinuria, cobalamin(cbl)C deficiency type (OMIM 277400), is the most common autosomal recessive inherited disorder of intracellular cobalamin metabolism caused by mutations in the MMACHC gene (OMIM 609831), of which more than 100 mutations have been identified to date. In this study, we only identified a coding mutation in one allele at the MMACHC gene locus, and no large fragments deletion or duplication were found. Up to now, only three epimutation cblC cases were reported. Read More

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Implementation of second-tier tests in newborn screening for the detection of vitamin B related acquired and genetic disorders: results on 258,637 newborns.

Orphanet J Rare Dis 2021 Apr 30;16(1):195. Epub 2021 Apr 30.

Sección de Errores Congénitos del Metabolismo-IBC, Servicio de Bioquímica Y Genética Molecular, Hospital Clínic de Barcelona, C/ Mejía Lequerica S/N, Edificio Helios III, 08028, Barcelona, Spain.

Background: Alteration of vitamin B metabolism can be genetic or acquired, and can result in anemia, failure to thrive, developmental regression and even irreversible neurologic damage. Therefore, early diagnosis and intervention is critical. Most of the neonatal cases with acquired vitamin B deficiency have been detected by clinical symptoms and only few of them trough NBS programs. Read More

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Classical homocystinuria, is it safe to exercise?

Mol Genet Metab Rep 2021 Jun 26;27:100746. Epub 2021 Mar 26.

Center for Molecular Diseases, Division of Genetic Medicine, Lausanne University Hospital and University of Lausanne, Lausanne, Switzerland.

Background Cystationine β-synthase (CBS) deficiency is a genetic disorder characterized by severe hyperhomocysteinemia and thrombotic complications. In healthy individuals, physical exercise may result in a transient increase in plasma total homocysteine (tHcy) raising the possibility that exercise might be detrimental in CBS deficiency. Our main objective was to determine plasma tHcy kinetics in response to physical exercise in homocystinuria patients. Read More

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Dysregulation of homocysteine homeostasis in acute intermittent porphyria patients receiving heme arginate or givosiran.

J Inherit Metab Dis 2021 Apr 16. Epub 2021 Apr 16.

Norwegian Porphyria Centre (NAPOS), Department of Medical Biochemistry and Pharmacology, Haukeland University Hospital, Bergen, Norway.

Acute intermittent porphyria (AIP) is a rare metabolic disease caused by mutations within the hydroxymethylbilane synthase gene. Previous studies have reported increased levels of plasma total homocysteine (tHcy) in symptomatic AIP patients. In this study, we present long-term data for tHcy and related parameters for an AIP patient cohort (n = 37) in different clinical disease-states. Read More

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The lysosomal protein ABCD4 can transport vitamin B across liposomal membranes in vitro.

J Biol Chem 2021 Apr 9:100654. Epub 2021 Apr 9.

Faculty of Pharmaceutical Sciences, Hiroshima International University, Kure, Japan.

Vitamin B (cobalamin) is an essential micronutrient for human health, and mutation and dysregulation of cobalamin metabolism are associated with serious diseases, such as methylmalonic aciduria and homocystinuria. Mutations in ABCD4 or LMBRD1, which encode the ATP-binding cassette (ABC) transporter ABCD4 and lysosomal membrane protein LMBD1, respectively, lead to errors in cobalamin metabolism, with the phenotype of a failure to release cobalamin from lysosomes. However, the mechanism of transport of cobalamin across the lysosomal membrane remains unknown. Read More

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Obsessive-Compulsive Symptoms as a Manifestation of Homocystinuria.

Case Rep Psychiatry 2021 20;2021:5523453. Epub 2021 Mar 20.

Centro Hospitalar Barreiro Montijo, Barreiro, Portugal.

Homocystinuria is a rare autosomal recessive metabolic disorder due to a defect in the cystathionine -synthase (CBS) that leads to high homocysteine plasma levels. Psychiatric symptoms secondary to homocystinuria have been described in the literature; however, there is a lack of information about obsessive-compulsive symptoms correlated to this disorder. We describe the case of a 39 years old man, diagnosed with homocystinuria in childhood, with no previous psychiatric history that presented obsessive-compulsive disorder (OCD) like symptoms, as a manifestation of homocystinuria. Read More

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Combined Genome, Transcriptome and Metabolome Analysis in the Diagnosis of Childhood Cerebellar Ataxia.

Int J Mol Sci 2021 Mar 15;22(6). Epub 2021 Mar 15.

Instituto de Investigación Biosanitaria ibs.GRANADA, 18012 Granada, Spain.

Ataxia in children is a common clinical sign of numerous neurological disorders consisting of impaired coordination of voluntary muscle movement. Its most common form, cerebellar ataxia, describes a heterogeneous array of neurologic conditions with uncountable causes broadly divided as acquired or genetic. Numerous genetic disorders are associated with chronic progressive ataxia, which complicates clinical management, particularly on the diagnostic stage. Read More

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Redox-Linked Coordination Chemistry Directs Vitamin B Trafficking.

Acc Chem Res 2021 04 2;54(8):2003-2013. Epub 2021 Apr 2.

Department of Biological Chemistry, Michigan Medicine, University of Michigan, Ann Arbor, Michigan 48109, United States.

Metals are partners for an estimated one-third of the proteome and vary in complexity from mononuclear centers to organometallic cofactors. Vitamin B or cobalamin represents the epitome of this complexity and is the product of an assembly line comprising some 30 enzymes. Unable to biosynthesize cobalamin, mammals rely on dietary provision of this essential cofactor, which is needed by just two enzymes, one each in the cytoplasm (methionine synthase) and the mitochondrion (methylmalonyl-CoA mutase). Read More

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Cobalamin J disease detected on newborn screening: Novel variant and normal neurodevelopmental course.

Am J Med Genet A 2021 06 17;185(6):1870-1874. Epub 2021 Mar 17.

Division of Genetics and Metabolism, Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota, USA.

Cobalamin J disease (CblJ) is an ultra-rare autosomal recessive disorder of intracellular cobalamin metabolism associated with combined methylmalonic acidemia and homocystinuria. It is caused by pathogenic variants in ABCD4, which encodes an ATP-binding cassette (ABC) transporter that affects the lysosomal release of cobalamin (Cbl) into the cytoplasm. Only six cases of CblJ have been reported in the literature. Read More

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Molecular evaluation of exon 8 cystathionine rs5742905T T>C gene polymorphism and determination of its frequency, distribution pattern, and association with susceptibility to Coronary Artery Disease. In North Indian Population.

Cardiovasc Hematol Disord Drug Targets 2021 Mar 15. Epub 2021 Mar 15.

Department of Biochemistry, Maulana Azad Medical College, University of Delhi. India.

Background: The protein coded by cystathionine β synthase (CBS) gene act as a catalyzer, converts homocysteine to cystathionine. Impairment of CBS gene leads to homocystinuria by cystathionine β synthase deficiency which is linked to Coronary Artery Disease. A number of polymorphisms study have been performed in cystathione β synthase gene. Read More

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Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type.

Orphanet J Rare Dis 2021 03 10;16(1):125. Epub 2021 Mar 10.

Department of Pediatric Endocrinology and Genetic, Xinhua Hospital, Shanghai Institute for Pediatric Research, Shanghai Jiao Tong University School of Medicine, 1665 Kongjiang Road, Yangpu District, Shanghai, 200092, China.

Background: Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of cobalamin metabolism, and different approaches have been applied to its prenatal diagnosis. To evaluate the reliability of biochemical method for the prenatal diagnosis of cblC defect, we conducted a retrospective study of our 10-year experience at a single center.

Methods: 248 pregnancies whose probands were diagnosed as cblC defect were referred to our center for prenatal diagnosis from January 2010 to December 2019. Read More

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Homocystinuria patient and caregiver survey: experiences of diagnosis and patient satisfaction.

Orphanet J Rare Dis 2021 03 10;16(1):124. Epub 2021 Mar 10.

Division of Evolution and Genomic Sciences, Institute of Human Development, University of Manchester, Manchester, UK.

Background: The main genetic causes of homocystinuria are cystathionine beta-synthase (CBS) deficiency and the remethylation defects. Many patients present in childhood but milder forms may present later in life. Some countries have newborn screening programs for the homocystinurias but these do not detect all patients. Read More

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Homocystinuria in a Family with Novel Cystathionine Beta Synthase Gene Mutations.

Clin Lab 2021 Feb;67(2)

Background: Classic homocystinuria is caused by cystathionine beta synthase deficiency owing to genetic mutations. The most common symptoms are ectopia lentis, osteoporosis, thrombosis, and mental retardation. This disease is prone to misdiagnosis and delayed diagnosis. Read More

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February 2021

Autism: Screening of inborn errors of metabolism and unexpected results.

Autism Res 2021 05 19;14(5):887-896. Epub 2021 Feb 19.

Department of Pediatric and Adolescent Mental Health and Diseases, Gazi University School of Medicine, Ankara, Turkey.

In this study, the aim was to examine patients with inborn errors of metabolism (IEM) who presented with only autism, without any other findings, to suggest any other neurological and genetic disorders. To investigate IEM, data of the hospital records of 247 patients who were referred from pediatric psychiatric to pediatric metabolism outpatient clinics due to further evaluation of autism spectrum disorders (ASD) were examined. Among them, 237 patients were evaluated for IEM leading to ASDs. Read More

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The first Saudi baby with classic homocystinuria diagnosed by universal newborn screening.

Saudi Med J 2021 Feb;42(2):219-222

From the Department of Pediatrics (AlAnzi, Mohamed); from the Department of Biochemical laboratory (Al Harbi, AlFaifi), Prince Sultan Military Medical City; from the Prince Abdullah bin Khalid Celiac Disease Research Chair (Mohamed), King Saud University; and from the Department of Pediatrics (Mohamed), College of Medicine, AlFaisal University, Riyadh, Kingdom of Saudi Arabia.

Classic homocystinuria (CH) is an inborn error of metabolism caused by cystathionine beta-synthase enzyme deficiency. Affected patients present with intellectual disability and other comorbidities. If diagnosed early in infancy and started treatment, inevitable complications can be prevented. Read More

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February 2021

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

Children (Basel) 2021 Feb 5;8(2). Epub 2021 Feb 5.

1st Department of Pediatrics, Aristotle University of Thessaloniki, Hippokratio General Hospital, 546 42 Thessaloniki, Greece.

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. Read More

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February 2021

MMADHC premature termination codons in the pathogenesis of cobalamin D disorder: Potential of translational readthrough reconstitution.

Mol Genet Metab Rep 2021 Mar 27;26:100710. Epub 2021 Jan 27.

Biocruces Bizkaia Health Research Institute, Barakaldo, Spain.

Mutations in the gene cause cobalamin D disorder (cblD), an autosomal recessive inborn disease with defects in intracellular cobalamin (cbl, vitamin B12) metabolism. CblD patients present methylmalonic aciduria (MMA), homocystinuria (HC), or combined MMA/HC, and usually suffer developmental delay and cognitive deficits. The most frequent genetic alterations associated with disease generate MMADHC truncated proteins, in many cases due to mutations that create premature termination codons (PTC). Read More

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A high frequency and geographical distribution of MMACHC R132* mutation in children with cobalamin C defect.

Amino Acids 2021 Feb 30;53(2):253-264. Epub 2021 Jan 30.

Pediatric Neurology Unit, Department of Pediatrics, PGIMER, Chandigarh, India.

Cobalamin C defect is caused by pathogenic variants in the MMACHC gene leading to impaired conversion of dietary vitamin B into methylcobalamin and adenosylcobalamin. Variants in the MMACHC gene cause accumulation of methylmalonic acid and homocysteine along with decreased methionine synthesis. The spectrum of MMACHC gene variants differs in various populations. Read More

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February 2021

Molecular and biochemical investigations of inborn errors of metabolism-altered redox homeostasis in branched-chain amino acid disorders, organic acidurias, and homocystinuria.

Free Radic Res 2021 Jan 27:1-14. Epub 2021 Jan 27.

Department of Biochemistry, All India Institute of Medical Sciences, Bhopal, Madhya Pradesh, India.

India, resembling other developing nations, is confronting a hastening demographic switch to non-communicable diseases. Inborn errors of metabolism (IEM) constitute a varied heterogeneous group of disorders with variable clinical appearance, primarily in the pediatric populace. Congenital deformities and genetic disorders are significant for mortality throughout the world, and the Indian scenario is not very different. Read More

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January 2021

Cases of inborn errors of metabolism diagnosed in children with autism.

Ideggyogy Sz 2021 01;74(1-2):67-72

Health Science University, Prof. Dr. Cemil Taşcıoğlu City Hospital, Department of Pediatrics, Istanbul, Turkey.

Background And Purpose: Autism spectrum disorder is a neurodevelopmental disorder with a heterogeneous presentation, the etiology of which is not clearly elucidated. In recent years, comorbidity has become more evident with the increase in the frequency of autism and diagnostic possibilities of inborn errors of metabolism.

Methods: One hundred and seventy-nine patients with diagnosis of autism spectrum disorder who presented to the Pediatric Metabolism outpatient clinic between 01/September/2018-29/February/2020 constituted the study population. Read More

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January 2021

Derangement of hepatic polyamine, folate, and methionine cycle metabolism in cystathionine beta-synthase-deficient homocystinuria in the presence and absence of treatment: Possible implications for pathogenesis.

Mol Genet Metab 2021 02 11;132(2):128-138. Epub 2021 Jan 11.

Medicine and University of Colorado School of Medicine, Aurora, CO 80045, USA.

Cystathionine beta-synthase deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. Our knowledge of the metabolic changes induced in HCU are based almost exclusively on data derived from plasma. In the present study, we present a comprehensive analysis on the effects of HCU upon the hepatic metabolites and enzyme expression levels of the methionine-folate cycles in a mouse model of HCU. Read More

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February 2021

Outcomes of patients with cobalamin C deficiency: A single center experience.

JIMD Rep 2021 Jan 8;57(1):102-114. Epub 2020 Nov 8.

Division of Clinical and Metabolic Genetics, Department of Pediatrics The Hospital for Sick Children Toronto Ontario Canada.

Biallelic variants in results in the combined methylmalonic aciduria and homocystinuria, called cobalamin (cbl) C (cblC) deficiency. We report 26 patients with cblC deficiency with their phenotypes, genotypes, biochemical parameters, and treatment outcomes, who were diagnosed and treated at our center. We divided all cblC patients into two groups: group 1: SX group: identified after manifestations of symptoms (n = 11) and group 2: NB group: identified during the asymptomatic period via newborn screening (NBS) or positive family history of cblC deficiency (n = 15). Read More

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January 2021

Liver transplant as a curative treatment in a pediatric patient with classic homocystinuria: A case report.

Am J Med Genet A 2021 04 14;185(4):1247-1250. Epub 2021 Jan 14.

Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota, USA.

We report a patient with homocystinuria and hyperoxaluria who was cured of homocystinuria-related disease following liver transplant. The patient was diagnosed with homocystinuria as a newborn and was treated with dietary modifications and supplements. At 22 months, he passed a calcium oxalate stone and was found to have numerous bilateral kidney stones. Read More

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Cardiovascular findings in classic homocystinuria.

Mol Genet Metab Rep 2020 Dec 10;25:100693. Epub 2020 Dec 10.

Medical Genetics Service, Hospital de Clínicas de Porto Alegre, RS, Brazil.

Objective: describe cardiovascular findings from echocardiograms and electrocardiograms in patients with Classic Homocystinuria.

Methods: this retrospective exploratory study evaluated fourteen subjects with Classic Homocystinuria (median age = 27.3 years; male  = 8, B6-non-responsive  = 9 patients), recruited by convenience sampling from patients seen Hospital de Clínicas de Porto Alegre (Brazil), between January 1997 and July 2020. Read More

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December 2020