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Congenital afibrinogenemia is a rare autosomal recessive blood disorder that accompanies thrombotic complications and is associated with bleeding tendency. The management of these opposing complications remains a challenge. Endovascular treatment (EVT) for peripheral arterial thrombosis has not been described in previous studies. A 57-year-old man with congenital afibrinogenemia developed back pain and left lower leg pain. The cause of the pain was confirmed to be renal infarction and lower extremity arterial thrombosis by Doppler ultrasound and contrast-enhanced computed tomography. He was treated with EVT for the lower extremity arterial thrombosis, leading to an excellent short-term improvement without bleeding.

Congenital afibrinogenemia is a rare autosomal recessive disorder that is caused by defects in the fibrinogen. Fibrinogen is a hexameric glycoprotein made of two pairs of three homologous polypeptide chains including Aα, Bβ, and γ that are encoded by three genes named FGA, FGB, and FGG. We aim to study four Iranian families who were referred to our lab for molecular diagnosis of afibrinogenemia. Genomic DNA was extracted from whole blood and Sanger sequencing was performed using primers for all exons and exon-intron junctions of FGA, FGB, and FGG genes. Pathogenicity of the variants was predicted using different in-silico tools and was interpreted according to the American College of Medical Genetics and Genomics guideline. We found three types of mutations in the studied families; two were in the FGA gene and one was in the FGB gene including a nonsense, a novel splicing mutation, and two deletion ones. The nonsense and the deletion mutations may cause a truncated protein and are likely pathogenic and pathogenic, respectively. The novel mutation of splicing found in the FGB gene is a pathogenic one and can break the wild-type acceptor site. Studying mutations in afibrinogenemia patients can expand our knowledge about this disease in Iran.

Congenital afibrinogenemia is a rare autosomal recessive hematologic disorder that results in coagulopathy due to the complete lack of fibrinogen production. While the common manifestation of the disease entails a bleeding diathesis, these patients are also at high risk of thromboembolic event due to abnormal coagulation cascade. We present a case in which a patient with congenital afibrinogenemia complicated by chronic thromboembolic pulmonary hypertension undergoes pulmonary thromboendarterectomy requiring cardiopulmonary bypass and deep hypothermic circulatory arrest. We discuss the clinical management technique with the use of human fibrinogen concentrate. We also discuss the potential safety implications and recent literature involving the use of human fibrinogen concentrate during cardiac surgery involving cardiopulmonary bypass and deep hypothermic circulatory arrest.

INTRODUÇÃO: A afibrinogenemia congênita, também conhecida como síndrome do fibrinogênio circulante indetectável, é um distúrbio autossômico recessivo extremamente raro, estimado em um a cada um milhão de habitantes. É uma alteração advinda de uma anormalidade em indivíduos homozigotos ou heterozigotos que apresentam mutações relacionadas ao gene que codifica a cadeia ? do fibrinogênio sendo estas alterações mais comuns em casos de consanguinidade e principalmente relacionadas ao gene FGA. As manifestações clínicas dessa condição se relacionam a ausência do fibrinogênio com hemorragias variáveis, podendo cursar até com óbito. O diagnóstico se dá através de uma exaustiva investigação laboratorial e o manejo advém da reposição do fibrinogênio ausente. OBJETIVOS: Relatar o caso de uma paciente com afibrinogenemia congênita que chegou ao atendimento emergencial com dor abdominal associada a vômitos. RESULTADOS: Paciente do sexo feminino, 6 anos, com diagnóstico prévio de afibrinogenemia congênita desde o primeiro mês de vida. Foi internada, durante 8 dias, devido a uma dor abdominal em região periumbilical. Nessa ocasião, fazia uso de concentrado de fibrinogênio (haemocomplettan®), uma vez na semana, sem melhora dos níveis laboratoriais de fibrinogênio, os quais persistiram extremamente baixos. A angiotomografia computadorizada de abdômen demonstrou ascite de moderado grau e hemoperitônio (fotografia 2), assim como, lesão esplênica com sangramento ativo (fotografia 1), responsável pela anemia evidenciada em exames laboratoriais. A conduta médica constituiu-se em jejum, repouso, solicitação de crioprecipitado, concentrados de hemácias, uso de haemocomplettan® em dias alternados e prescrição de ceftriaxona (rocefin®) juntamente com metronidazol, além da possibilidade de indicação de laparotomia exploratória. A paciente respondeu bem ao tratamento conservador, com resolução da anemia, melhora da dor abdominal, elevação do fibrinogênio e desaparecimento do líquido livre observado em ultrassonografia diária. Desse modo, não houve necessidade de intervenção cirúrgica e a paciente foi liberada após 8 dias de internação. DISCUSSÃO: Clinicamente, eventos traumáticos e invasivos, como cirurgias predispõem ao sangramento nesses pacientes. No presente relato de caso, se o tratamento conservador não fosse suficiente, a execução da laparotomia exploratória seria necessária, acrescentando riscos à vida do paciente. Sendo assim, enfatiza-se a importância de um tratamento apropriado com reposição de fibrinogênio, crioprecipitado e plasma fresco congelado para evitar cirurgias desnecessárias. Apesar de poder ocorrer hemorragias potencialmente fatais, como na ruptura esplênica, os pacientes com essa doença possuem prognóstico favorável quando tratados adequadamente. Também há uma susceptibilidade dos indivíduos com afibrinogenemia ter ruptura esplênica sem a ocorrência de um trauma, sendo ainda esse caso pouco compreendido nas literaturas. CONCLUSÃO: A sintomatologia clínica da afibrinogenemia é variável e caracteriza-se, principalmente, por hemorragias espontâneas ou pós traumáticas de intensidade leve a grave. Em geral, os pacientes portadores dessa doença possuem um prognóstico favorável com o diagnóstico precoce e tratamento adequado, como visto na paciente deste relato de caso. Por fim, por ser uma doença crônica e sem cura, é imprescindível a orientação dos cuidadores sobre a doença e atividades traumáticas que podem ocasionar sangramentos e, consequentemente, desencadear quadros potencialmente graves.

Fibrinogen replacement therapy is a treatment mainstay for patients with afibrinogenemia and significant bleeding. A male infant with congenital afibrinogenemia and several spontaneous hemarthroses commenced cryoprecipitate prophylaxis but developed severe urticarial reactions. He transitioned to a human fibrinogen concentrate (HFC) (RiaSTAP®, CSL Behring; 70 mg/kg biweekly) but continued experiencing hemarthroses (estimated annualized bleeding rate [ABR]: 5‐6) and severe anaphylactic reactions, despite pre‐ and postinfusion medications. Following switching to a new HFC (Fibryga®, Octapharma; 50 mg/kg biweekly), ABR was 0‐1 with no further infusion reactions. Aged 9 years, because of limited quality of life, development of obesity and fatty liver disease, he underwent orthotopic liver transplant (OLT) under HFC coverage. Pharmacokinetic analysis guided presurgical fibrinogen levels > 150 mg/dL. No intraoperative HFC infusions were required. Coagulation profile and fibrinogen levels remained within normal limits during and posttransplant. To our knowledge, this is the first pediatric report of afibrinogenemia successfully treated with OLT.

Congenital afibrinogenemia is a rare disorder characterized by a lack of detectable fibrinogen. The mainstay of treatment for acute bleeding episodes or perioperative management is replacement with fibrinogen concentrate or fibrinogen-containing blood products. The development of neutralizing antibodies and severe allergic reactions to fibrinogen replacement is rarely reported in afibrinogenemia patients. Here the treatment regimen is described for a 6-year-old girl with a severe allergic reaction to multiple fibrinogen-containing products who became refractory to treatment because of a presumed inhibitor to fibrinogen.

Contains fulltext : 218309.pdf (Publisher’s version ) (Open Access) Congenital afibrinogenemia is a rare autosomal recessive disorder associated with an increased risk of hemorrhage, thrombosis, and obstetric complications. This case series of 4 pregnancies in 2 related patients seeks to address the key clinical question of the necessary doses of fibrinogen concentrate during pregnancy and puerperium. One pregnancy without the prophylactic use of fibrinogen concentrate resulted in spontaneous abortion. The second pregnancy was complicated by a subchorionic hematoma despite the prophylactic administration of fibrinogen concentrate to maintain the plasma trough levels at >/=0.6 g/L. Labor was complicated by postpartum hemorrhage with a blood loss volume of 1480 cc. Two weeks later, the patient presented with postpartum thrombosis. The other 2 pregnancies were uncomplicated with fibrinogen trough levels >/=1.0 g/L during pregnancy and >/=1.5 g/L during labor. These cases illustrate that during pregnancy, patients may benefit from fibrinogen trough levels >/=1.0 g/L. In addition, the increased risk of postpartum thrombosis with prolonged fibrinogen supplementation warrants personalized postpartum advice that is guided by postpartum blood loss.

Although the inherited quantitative and qualitative disorders of fibrinogen are rare, in the course of time patients may develop complications including episodes of arterial and venous thrombosis. It can be useful to complete the laboratory assessment of these clinical conditions with the evaluation of the haemorheological profile. The data obtained from this study showed that congenital afibrinogenemia was characterized by a primary plasma hypoviscosity, whereas congenital dysfibrinogenemia by a primary plasma hyperviscosity. Both these haemorheological alterations may concur, with different mechanisms, to the pathogenesis of thrombotic vascular complications.

The objective is to report a patient with congenital afibrinogenemia and vascular abnormalities and also review the clinical and molecular issues. The female proband, diagnosed with congenital afibrinogenemia, was admitted at a hospital due to a hemorrhagic shock. Angiotomography revealed ectasias from ascending branch to the abdominal aorta, with multiple calcifications and atheroma. Clinical exome identified a homozygous novel pathogenic variant in FGG gene. In our review the main symptom, at diagnosis, was umbilical cord bleeding and the degree of clinical involvement varied from asymptomatic to severe. The FGA gene was the most affected and possible hot spots were observed. Variants considered as loss of function were the most frequent. The association of vascular abnormalities in a patient with congenital afibrinogenemia alerts for a closer follow-up of vascular issues in these patients.

Introduction Congenital afibrinogenemia is a severe bleeding disorder, sometimes manifesting as thrombosis and/or pregnancy complications. Intracranial haemorrhage (ICH) constitutes the major cause of death in this disease. Methods We present the case of a male patient with congenital afibrinogenemia, who presented with recurrent intracranial hemorrhages, despite prophylactic fibrinogen substitution. We also review the literature for the risk of intracranial hemorrhages in afibrinogenemia. Result Molecular analysis revealed a novel homozygous missense mutation in FGB exon 5, p.Cys241 Tyr, that was named "Fibrinogen Krakow V". Discussion and conclusion Intracranial hemorrhage is a severe manifestation of afibrinogenemia, also in children. The clinical presentation of afibrinogenemia is variable. Fibrinogen substitution carries a risk of thrombotic complications.

Platelets play an important role in hemostasis through platelet plug formation by a phenomenon of adhesion; activation; secretion and aggregation. Defects in platelet hemostatic mechanisms can be congenital or acquired. Congenital platelet disorders are rare and manifestations range from asymptomatic to sometimes severe bleeding. The disorders arise due to diverse mechanisms. Congenital platelet disorders include thrombocytopathies and thrombocytopenia (platelet count 450 x 109/L). Congenital thrombocytopathies include disorders of adhesion like von Willebrand's disease or Bernard-Soulier syndrome. The disorders of aggregation include congenital afibrinogenemia and Glanzmann thrombasthenia. Disorders of storage granules are gray platelet syndrome and Quebec platelet disorder. Congenital thrombocythopathy and thrombocytopenia often occur in conjunction. In this article, we have a detailed literature review of these rare thrombocytopathies, their presentation and treatment.

Introduction: Congenital afibrinogenemia is a rare autosomal recessive disorder characterized by bleeding that varies from mild to severe and by complete absence or extremely low levels of plasma and platelet fibrinogen. Hypofibrinogenemia is characterized by fibrinogen levels Objective: In this study, we analyzed fibrinogen beta chain gene mutations in Turkish afibrinogenemia and hypofibrinogenemia patients. Methods: We evaluated 20 afibrinogenemia and hypofibrinogenemia patients and 80 healthy controls. We have sequenced all exons of the FGB gene using the DNA isolated from the peripheral blood samples of patients and controls. Results and Conclusion: We found a nonsense mutation in exon 4 at nucleotide 630 that encoded serine amino acid, and in the same exon a missense mutation of T to C at nucleotide 647, resulting in a transition from leucine to proline (p.L198P) in a child with hypofibrinogenemia. These mutations have been shown for the first time in the same patient of Turkish descent. Furthermore, there was a novel heterozygous guanine-to-adenine nucleotide change in exon 3. This caused the change of arginine amino acid to threonine amino acid at position 136 (p.A136T) in a protein, which has not been described in the literature before.

Background and aims Congenital afibrinogenemia is a rare coagulation disorder resulting from a deficiency in fibrinogen. This study assessed the pharmacokinetics, surrogate efficacy and safety of FIB Grifols, a new human plasma-derived fibrinogen concentrate, to treat congenital afibrinogenemia. Methods Eleven adult patients from a multinational, phase 1–2, prospective, open-label, single-arm, uncontrolled clinical study received a single infusion of FIB Grifols, 70 mg/kg bw. Fibrinogen pharmacokinetics (fibrinogen activity: Clauss method; antigen plasma concentrations: ELISA) and efficacy parameters were determined over 14 days after infusion. Efficacy endpoints were the mean change on plasma maximum clot firmness (MCF) on viscoelastic testing and coagulation tests 1-hour post-infusion, and correlation with fibrinogen levels throughout. Safety parameters were also assessed. Results For the Clauss method, (mean [standard deviation]) baseline adjusted Cmax was 1.99 (0.40) g/L, reached 1.76 (1.00) h after infusion, and half-life was 76.94 (20.21) h. Using ELISA, Cmax after FIB Grifols infusion was 2.88 (0.86) mg/mL, with a tmax of 3.06 (2.24) h. Fibrinogen activity and antigen concentrations showed statistically significant correlation of 0.9120 (P Conclusions The pharmacokinetic profile of functionally active FIB Grifols was established, hemostasis was restored, and FIB Grifols was safe and well tolerated in fibrinogen-deficient patients.

Background Patients with congenital afibrinogenemia suffer from spontaneous recurrent severe bleeding. While fibrinogen concentrates are known to effectively treat bleeding episodes, thrombotic complications often occur upon replacement therapy, rendering clinical management highly challenging. Case Presentation We hereby report a case of combined afibrinogenemia and congenital antithrombin deficiency manifested by recurrent life-threatening bleeding, as well as spontaneous severe arterial occlusion, such as acute coronary syndrome and stroke, and venous thromboses like pulmonary embolism. Secondary fibrinogen prophylaxis is recommended following any initial life-threatening bleeding episode in patients with afibrinogenemia, yet the high associated risk of thrombosis illustrates the complexity of choosing the most effective prophylaxis strategy combining fibrinogen concentrate with antithrombotic agent for optimal protection against the risk of both severe bleeding and thrombosis. For our patient, the thrombin generation assay objectively confirmed her prothrombotic tendency. Conclusion This case may help us better understand the pathophysiology of arterial thrombosis in afibrinogenemia, while highlighting the difficulty of managing such complications.

Background: Congenital fibrinogen disorders (CFDs) comprise about 10% of rare bleeding disorders (RBDs). CFDs are divided into two groups of quantitative (afibrinogenemia and hypofibrinogenemia) with autosomal recessive inheritance pattern, and qualitative (dysfibrinogenemia, hypodysfibrogenemia) disorders, mainly with autosomal dominant inheritance pattern. Sistan and Baluchestan Province in Iran, with its high rate of consanguineous marriages, has a high incidence of RBDs including CFD. In the current study, we report clinical manifestations of patients with CFDs.Methods: Twelve new Iranian patients from Sistan and Baluchestan Province with different types of CFDs were selected for this study. Diagnosis of CFDs was based on clinical features and familial history followed by laboratory assessment by routine and specific coagulation tests including prothrombin time (PT) and activated partial time tests (APTT), as well as FI activity assay by Clauss method.Results: Out of 12 patients, 3(25%) had afibrinogenemia, 7(58.3%) had hypofibrinogenemia while 2(16/7%) were suspected of having dysfibrinogenemia. Although umbilical cord bleeding (UCB) 9(75%) was the most common clinical presentation among the study population, this feature was not observed among patients with dysfibrinogenemia. Hematoma (100%) was the most common presentation of patients with dysfibrinogenemia. Conclusion: Results of this study revealed that some clinical presentations are the diagnostic features of CFDs and can be used for precise and in-time diagnosis CFDs in conjunction with family history and laboratory findings.Keywords: Fibrinogen Deficiency; Congenital Afibrinogenemia; Blood Coagulation Disorder; Afibrinogenemia

Congenital fibrinogen disorders are rare pathologies of the hemostasis, comprising quantitative (afibrinogenemia, hypofibrinogenemia) and qualitative (dysfibrinogenemia and hypodysfibrinogenemia) disorders. The clinical phenotype is highly heterogeneous, being associated with bleeding, thrombosis, or absence of symptoms. Afibrinogenemia and hypofibrinogenemia are the consequence of mutations in the homozygous, heterozygous, or compound heterozygous state in one of three genes encoding the fibrinogen chains, which can affect the synthesis, assembly, intracellular processing, stability, or secretion of fibrinogen. In addition to standard coagulation tests depending on the formation of fibrin, diagnostics also includes global coagulation assays, which are effective in monitoring the management of replacement therapy. Genetic testing is a key point for confirming the clinical diagnosis. The identification of the precise genetic mutations of congenital fibrinogen disorders is of value to permit early testing of other at risk persons and better understand the correlation between clinical phenotype and genotype. Management of patients with afibrinogenemia is particularly challenging since there are no data from evidence-based medicine studies. Fibrinogen concentrate is used to treat bleeding, whereas for the treatment of thrombotic complications, administered low-molecular-weight heparin is most often. This review deals with updated information about afibrinogenemia and hypofibrinogenemia, contributing to the early diagnosis and effective treatment of these disorders.

Background Congenital fibrinogen deficiency is one of the rare inherited coagulation disorders. Congenital fibrinogen deficiency complicated with a hematological malignancy can be life threatening. Case We present a four-year-old girl with congenital fibrinogen deficiency complicated with acute lymphoblastic leukemia. Conclusion This case aims to highlight therapeutic approaches for the management of afibrinogenemia patients with acute leukemia.

In this case report, we examine the behavior of plasma viscosity, explored at high and low shear rates, and erythrocyte aggregation in two patients with congenital afibrinogenemia, a clinical disorder firstly described in 1920 and that has an estimated incidence of 1 : 1-200 0000. The two hemorheological parameters examined by us showed a marked decrease in both patients, in one of whom erythrocyte aggregation was even undetectable. Keeping in mind that spontaneous thrombosis (venous and arterial) has been often described in congenital afibrinogenemia, it can be hypothesized that the decrease in plasma viscosity and erythrocyte aggregation might cause a reduction of the endothelial synthesis and release of nitric oxide through the fall of the wall shear stress.

Fibrinogen is a complex protein playing a major role in coagulation. Congenital afibrinogenemia, characterized by the complete absence of fibrinogen, is associated with major hemostatic defects. Even though the clinical course is unpredictable and can be completely different among patients, severe bleeding is the prominent symptom. Patients are also at increased risk of thrombosis and sometimes suffer from spontaneous spleen rupture, bone cysts and defective wound healing. Due to the relative rarity of afibrinogenemia, there are no evidence-based strategies for helping physicians in care of these patients. Fibrinogen supplementation is the keystone to prevent or treat bleeding events. In addition, fibrinogen, a pleiotropic protein with numerous physiological roles in immunity, angiogenesis and tissue repair, is involved in many diseases. Indeed, depletion of fibrinogen in animal models of infections, tumors and neurological diseases has an effect on the clinical course. The consequences for patients with afibrinogenemia still need to be investigated.

Background and Objectives A new fibrinogen concentrate Clottafact® was developed according to European guidelines on plasma-derived products. A post-authorization safety study was set up in 2009 as part of the risk management plan. This was a non-interventional, prospective, non-comparative, multicenter study of the use of fibrinogen concentrate for congenital afibrinogenemia in real-life medical practice in France. Materials and Methods The analysis was descriptive and performed on 3 subgroups: prophylaxis vs. on-demand treatment, age (

We readwith great interest the topical article by deMoerloose et al1 in Seminars in Thrombosis and Hemostasis regarding congenital afibrinogenemia. Accordingly, we recently corresponded anovelmutation in an afibrinogenemicpatientwith a proposed new pathological molecular mechanism underlying afibrinogenemia.2Wehave named this novelmutation “fibrinogenMartin”, and nowwish to expand our intial report to also describefindingswith thehypofibrinogenemic kindreds of the index patient. Fibrinogen is a 340 kDa glycoprotein comprising pairs of three polypeptide chains termed Aα, Bβ, and γ. Fibrinogen has a trinodular structure with a central nodule (E-domain) that contains the N-terminus of each chain and two lateral globular domains (D-domains) that contain the C-terminus of Bβand γ-chains. The E-domain is linked to the two D-domains by a coiled-coil triple helix structure.3,4 The three genes encoding fibrinogen Bβ (FGB), Aα (FGA), and γ (FGG), ordered from centromere to telomere, are clustered in a region of 50 kb on human chromosome 4q28.1,4 Congenital afibrinogenemia is an autosomal recessive bleeding disorder, referring to the total absence of plasma fibrinogen asmeasured by an antigenic assay, and is caused by variations in these genes, and associated with homozygous or compound heterozygous mutations, while hypofibrinogenemia is usually linked with heterozygous mutations.5 Mutations of FGB are less common and of particular interest since the Bβ-chain is considered the rate-limiting factor in the hepatic production of the fibrinogen hexamer.6 The estimated prevalence of congenital afibrinogenemia is 1 in 1,000,000,1 and according to our present knowledge, in Slovakia is 1 in 5,000,000.7 We recently performed genetic analysis of FGA, FGB, and FGG as well as coagulation tests in a patient with congenital afibrinogenemia plus his immediate family (i.e., his parents and two older sisters). The patient with congenital

Fibrinogen is a hexameric plasmatic glycoprotein composed of pairs of three chains (Aα, Bβ, and γ), which play an essential role in hemostasis. Conversion of fibrinogen to insoluble polymer fibrin gives structural stability, strength, and adhesive surfaces for growing blood clots. Equally important, the exposure of its non-substrate thrombin-binding sites after fibrin clot formation promotes antithrombotic properties. Fibrinogen and fibrin have a major role in multiple biological processes in addition to hemostasis and thrombosis, i.e., fibrinolysis (during which the fibrin clot is broken down), matrix physiology (by interacting with factor XIII, plasminogen, vitronectin, and fibronectin), wound healing, inflammation, infection, cell interaction, angiogenesis, tumour growth, and metastasis. Congenital fibrinogen deficiencies are rare bleeding disorders, characterized by extensive genetic heterogeneity in all the three genes: FGA, FGB, and FGG (enconding the Aα, Bβ, and γ chain, respectively). Depending on the type and site of mutations, congenital defects of fibrinogen can result in variable clinical manifestations, which range from asymptomatic conditions to the life-threatening bleeds or even thromboembolic events. In this manuscript, we will briefly review the main pathogenic mechanisms and risk factors leading to thrombosis, and we will specifically focus on molecular mechanisms associated with mutations in the C-terminal end of the beta and gamma chains, which are often responsible for cases of congenital afibrinogenemia and hypofibrinogenemia associated with thrombotic manifestations.

Background: Rarity of rare bleeding disorders (RBDs) is attributed to very low incidence based on ethnicity, distribution and complexity of diagnostic tools. There is scarcity of data on RBDs from Eastern India. This study aims to understand the distribution of RBDs in this region for better patient care.Methods: Retrospective study conducted on patients presented with symptoms/signs of bleeding from January 2018 to December 2019 (two years). Patients having bleeding manifestations from causes other than inherited coagulation disorders, IPDs, and vWD were included. Complete haemogram, peripheral blood smear, coagulation tests, vWD assay and platelet function tests were carried out.Results: Out of 2415 patients, 1570 were included after exclusion of other diseases. Immune Thrombocytopenia (ITP) and Hemophilia being excluded, 40/1570 (2.5%) patients were found to have RBDs. Median age was 11.6 years (range, 1.25-40 years). Most common was IPDs (2.9%, n=19); Glanzmann thrombasthenia was commonest (1.5%, n=10). vWD was second (1.7%, n=11) in occurrence; vWD type-III was the commonest subtype (0.9%, n=6). ICDs comprised 1.5% (n=10) of all patients; congenital afibrinogenemia (0.6%, n=4) was most common. Other ICDs prevalent in this cohort included FVII, FV, FX and FXIII deficiencies. Most common presentations were ecchymoses or prolonged bleeding from cut injuries or menorrhagia.Conclusions: RBDs may present in varied ways and are often difficult to diagnose correctly. Distribution of RBDs in this patient cohort differs from published literature from Western studies.