RESUMO
Mevalonate kinase deficiency is a group of rare metabolic autoinflammatory disorders that present with recurrent fevers, abdominal pain, arthralgias, adenopathy, and a variety of cutaneous manifestations. The skin findings may mimic cellulitis, erythema elevatum diutinum, IgA vasculitis, and Sweet syndrome, and there is often a morbilliform or urticarial rash and aphthous stomatitis. Mevalonate kinase deficiency is one of the identified monogenic variants that can cause very early onset inflammatory bowel disease (IBD). We present a rare case of a patient with mevalonate kinase deficiency, neonatal Sweet syndrome, and infantile-onset IBD, who has been successfully treated with canakinumab therapy.
Assuntos
Doenças Inflamatórias Intestinais , Deficiência de Mevalonato Quinase , Síndrome de Sweet , Vasculite Leucocitoclástica Cutânea , Recém-Nascido , Humanos , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/tratamento farmacológico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/diagnóstico , Doenças Inflamatórias Intestinais/tratamento farmacológicoRESUMO
BACKGROUND: Sweet syndrome (SS), also known as acute febrile neutrophilic dermatosis, is an immunologic syndrome characterized by widespread neutrophilic infiltration. Histiocytoid Sweet syndrome (H-SS) is a histopathologic variant of SS. While SS most commonly occurs in adults, this case report discusses an infant patient who presented with H-SS. CASE PRESENTATION: Through a multidisciplinary approach, this patient was also found to have very early onset inflammatory bowel disease (VEO-IBD) and Mevalonate kinase-associated disease (MKAD). While prior case studies have characterized an association between VEO-IBD and MKAD, there is no literature describing the association of all three diagnoses this case: H-SS, VEO-IBD and MKAD. Initiation of canakinumab in this patient resulted in successful control of the disease. CONCLUSIONS: This case highlights the importance of a multidisciplinary approach to rare diagnoses, and collaboration during cases with significant diagnostic uncertainty.
Assuntos
Doenças Inflamatórias Intestinais , Deficiência de Mevalonato Quinase , Síndrome de Sweet , Adulto , Humanos , Recém-Nascido , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Síndrome de Sweet/diagnóstico , Síndrome de Sweet/tratamento farmacológico , Síndrome de Sweet/etiologiaRESUMO
Hyperimmunoglobulin D syndrome (HIDS) is a hereditary autoinflammatory disease characterized by recurrent inflammatory attacks with fever, abdominal pain, lymphadenopathy, aphthous stomatitis, and skin lesions. There are few reports on HIDS patients complicated with macrophage activation syndrome (MAS); however, to our knowledge, there is no case of HIDS with recurrent MAS attacks. We report two pediatric patients initially diagnosed as Kawasaki disease and systemic juvenile idiopathic arthritis presented with recurrent MAS episodes with prolonged fever, skin rash, hepatosplenomegaly, cervical lymphadenopathy, aphthous stomatitis, headache, pancytopenia, hyperferritinemia, and hypofibrinogenemia, finally diagnosed as HIDS with a documented homozygous MVK gene mutation. This is the first report on recurrent MAS attacks due to HIDS in pediatric patients who were successful treated with corticosteroids and anti-IL-1 therapies. Thus, clinicians should be vigilantly investigated signs of autoinflammatory diseases in patients with recurrent MAS attacks during their disease course, and HIDS should be considered an underlying disease for triggering recurrent MAS attacks. We have also reviewed the current literature regarding HIDS cases complicated with a MAS attack and summarized their demographic, treatment, and outcome characteristics. Key points ⢠Hyperimmunoglobulin D syndrome should be considered in differential diagnosis in patients who experienced recurrent macrophage activation syndrome attacks.
Assuntos
Linfadenopatia , Síndrome de Ativação Macrofágica , Deficiência de Mevalonato Quinase , Estomatite Aftosa , Criança , Humanos , Síndrome de Ativação Macrofágica/diagnóstico , Síndrome de Ativação Macrofágica/tratamento farmacológico , Síndrome de Ativação Macrofágica/etiologia , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/tratamento farmacológico , FebreRESUMO
OBJECTIVES: Mevalonate kinase deficiency (MKD) is an autosomal recessive autoinflammatory disease characterized by recurrent systemic inflammation attacks. Despite interconnections with inflammation, thrombosis is rare or underreported in MKD. Our goal is to report evidence of uncontrolled inflammation as the cause of ischemic stroke. MATERIALS AND METHODS: Case report. RESULTS: A 39-year-old French-Canadian patient consulted for stroke. He reported a previous diagnosis of familial Mediterranean fever and hospitalizations nearly monthly since birth for recurrent inflammatory attacks despite colchicine prophylaxis. Attacks were triggered by infections or stress, lasted 3-7 days, and included fever up to 41°C, painful lymphadenopathies, abdominal pain, polyarthralgia and maculopapular rash. Stroke culminated his most recent inflammatory attack. Brain MRI confirmed an acute infarct, without chronic ischemic damage. Blood tests documented increased C-reactive protein, amyloid A and immunoglobulin-D. Prothrombotic and autoantibody tests, cervicocephalic CT-angiography, echocardiography, cardiac monitoring, and toxic screen were unremarkable. Infections were excluded. His only sister had similar attacks. In both cases, sequencing of 32 autoinflammatory-associated genes identified two pathogenic mevalonate kinase mutations. Their non-consanguineous parents, half-brother and four children were asymptomatic. Following treatment with anti-interleukin-1beta monoclonal antibodies, he no longer had inflammatory attacks or stroke in >4 years. CONCLUSION: This MKD patient experienced an ischemic stroke during an attack, attributed to uncontrolled inflammation. Investigations excluded other stroke etiologies. Recurrent febrile attacks starting before age 1 and lasting >3 days, gastrointestinal symptoms, painful lymphadenopathies, maculopapular rash, triggers, aphthous stomatitis, non-Mediterranean ancestry, and ineffectiveness of colchicine prophylaxis are consistent with MKD. Anti-interleukin-1 therapy prevents recurrent autoinflammatory attacks.
Assuntos
Exantema , AVC Isquêmico , Linfadenopatia , Deficiência de Mevalonato Quinase , Criança , Masculino , Humanos , Lactente , Adulto , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/tratamento farmacológico , Canadá , Inflamação/complicações , Febre/tratamento farmacológico , Colchicina/uso terapêutico , Exantema/complicações , Linfadenopatia/complicaçõesRESUMO
Hidradenitis Suppurativa (HS) is a chronic suppurative disease of the pilosebaceous unit. The current model of HS pathophysiology describes the condition as the product of hyperkeratinisation and inflammation at the hair follicular unit. Environmental factors (such as smoking and obesity), gender, genetic predisposition, and skin dysbiosis are considered the main pathogenic drivers of the disease. Autoinflammatory syndromes associated with HS are rare but may help to highlight the potential roles of autoinflammation and dysregulated innate immune system in HS. Therefore, it is of major relevance to increase the awareness about these diseases in order to improve the understanding of the disease and to optimize the management of the patients. Herein, we report for the first time, to our knowledge, two clinical cases of Hyper-IgD syndrome-associated HS. Hyper-IgD is an autoinflammatory syndrome caused by a mevalonate kinase deficiency (MKD), a key kinase in the sterol and isoprenoid production pathway. We describe the potentially shared pathophysiological mechanisms underpinning comorbid MKD-HS and propose therapeutic options for the management of these patients.
Assuntos
Hidradenite Supurativa , Deficiência de Mevalonato Quinase , Comorbidade , Hidradenite Supurativa/complicações , Humanos , Inflamação/complicações , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Pele , SíndromeRESUMO
INTRODUCTION: Mevalonate kinase deficiency (MKD) is a monogenic auto-inflammatory disease. Its manifestations range from partial MKD to mevalonic aciduria (MVA). All patients display a periodic fever, and MVA patients additionally exhibit severe neurological involvement. The objective of this work was to describe neurological manifestations of MKD. METHODS: A systematic literature review was performed from January 1990 to January 2022. Forty-five patients from 18 case reports and five cohort studies were included in the analysis. RESULTS: In cohort studies, the most-reported manifestations were headaches (41%) and fatigue (31%). Serious involvements including ataxia and developmental delay were described less than 1% of patients but 22-31% of case reports. They consistently appeared in the first years of life. Retinal dystrophy was frequently reported (31%) in case reports. Other manifestations, including uveitis, aseptic meningitis, and stroke remained rare. DISCUSSION: Severe neurological manifestations are rare in MKD but are responsible for major functional disabilities. They are present at onset and never appear at follow-up of patients with mild MKD. Conversely, headaches and fatigue are frequent symptoms that should be investigated. Visual examinations should be performed on the appearance of visual symptoms. The efficacy of anti-IL-1ß therapy on neurological manifestations should be further investigated.
Assuntos
Deficiência de Mevalonato Quinase , Fadiga/etiologia , Cefaleia/etiologia , Humanos , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/genéticaRESUMO
We report 7 years of follow-up data on ocular findings in a 2-month-old boy who presented with early-onset bilateral granulomatous panuveitis with subsequent development of secondary glaucoma and total cataract, along with multisystem involvement. He was diagnosed with mevalonate kinase deficiency (MKD), with a homozygous missense variant in exon-6 of the mevalonate kinase (MVK) gene on chromosome-12 that resulted in the substitution of aspartic acid for asparagine at codon 205 (p.Asn205Asp). Despite being managed with topical/systemic steroids and immunosuppression therapy with methotrexate and a short course of adalimumab, the patient continued to develop recurrent episodes of uveitis along with multisystem manifestations. The occurrence of early-onset uveitis is rare, as is the diagnosis of MKD.
Assuntos
Catarata , Glaucoma , Deficiência de Mevalonato Quinase , Uveíte , Adalimumab , Catarata/complicações , Catarata/etiologia , Glaucoma/complicações , Humanos , Lactente , Masculino , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/tratamento farmacológico , Uveíte/diagnóstico , Uveíte/tratamento farmacológico , Uveíte/etiologiaRESUMO
Mevalonic aciduria (MA) is the most severe clinical subtype of mevalonate kinase deficiency (MKD) caused by an inherited defect in the mevalonate pathway. The treatment of MKD focuses on the suppression of recurrent hyperinflammatory attacks using anti-inflammatory drugs. Recently, allogeneic hematopoietic stem cell transplantation (HCT) was shown to successfully ameliorate autoinflammatory attacks in patients with MKD. Here, we report a case of an infant who showed severe recurrent systemic inflammation and was diagnosed with MA. Although she responded to steroids, her symptoms relapsed after the dose was tapered, and organ deterioration occurred. Therefore, at the age of 11 months, HCT from a matched, unrelated donor was performed for curative treatment. However, at 50 days after transplantation, acute myeloid leukemia was diagnosed, which was chemo-refractory. A second HCT from her haploidentical father was performed to treat the acute myeloid leukemia, but the patient died of sepsis on day 4 after transplantation. This is the first report of malignancy following HCT for MA. Our findings suggest that normalizing the mevalonate pathway after HCT in patients with MKD impacts patients differently depending on the clinical spectrum and severity of disease.
Assuntos
Leucemia Mieloide Aguda/complicações , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Biomarcadores , Biópsia , Medula Óssea/patologia , Evolução Fatal , Feminino , Transplante de Células-Tronco Hematopoéticas , Humanos , Hibridização in Situ Fluorescente , Lactente , Leucemia Mieloide Aguda/diagnóstico , Leucemia Mieloide Aguda/terapia , Deficiência de Mevalonato Quinase/terapia , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Análise de Sequência de DNA , Avaliação de Sintomas , Transplante Haploidêntico , Sequenciamento do ExomaRESUMO
BACKGROUND: Mevalonate kinase deficiency (MKD) is a rare autoinflammatory condition caused by biallelic loss-of-function (LOF) mutations in mevalonate kinase (MVK) gene encoding the enzyme mevalonate kinase. Patients with MKD display a variety of non-specific clinical manifestations, which can lead to diagnostic delay. We report the case of a child presenting with vasculitis that was found by genetic testing to be caused by MKD, and now add this autoinflammatory disease to the ever-expanding list of causes of monogenic vasculitides. CASE PRESENTATION: A 2-year-old male presented with an acute 7-day history of high-grade fever, abdominal pain, diarrhoea, rectal bleeding and extensive purpuric and necrotic lesions, predominantly affecting the lower limbs. He had been suffering from recurrent episodes of fever from early in infancy, associated with maculopapular/petechial rashes triggered by intercurrent infection, and after vaccines. Extensive infection screen was negative. Skin biopsy revealed small vessel vasculitis. Visceral digital subtraction arteriography was normal. With a diagnosis of severe idiopathic cutaneous vasculitis, he was treated with corticosteroids and mycophenolate mofetil. Despite that his acute phase reactants remained elevated, fever persisted and the vasculitic lesions progressed. Next-generation sequencing revealed compound heterozygous mutation in MVK c.928G > A (p.V310M) and c.1129G > A (p.V377I) while reduced mevalonate enzyme activity was confirmed suggesting a diagnosis of MKD as a cause of the severe vasculitis. Prompt targeted treatment with IL-1 blockade was initiated preventing escalation to more toxic vasculitis therapies and reducing unnecessary exposure to cytotoxic treatment. CONCLUSIONS: Our report highlights the broad clinical phenotype of MKD that includes severe cutaneous vasculitis and emphasizes the need to consider early genetic screening for young children presenting with vasculitis to exclude a monogenic vasculitis which may be amenable to targeted treatment.
Assuntos
DNA/genética , Diagnóstico Tardio , Deficiência de Mevalonato Quinase/complicações , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Vasculite/etiologia , Biópsia , Pré-Escolar , Análise Mutacional de DNA , Diagnóstico Diferencial , Testes Genéticos , Genótipo , Humanos , Masculino , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/genética , Fenótipo , Fosfotransferases (Aceptor do Grupo Álcool)/metabolismo , Pele/patologia , Vasculite/diagnósticoRESUMO
Mevalonate kinase deficiency should be considered in patients with severe very-early-onset inflammatory bowel disease (IBD), especially in patients with a history of recurrent or chronic fever, peritoneal adhesions, and atypical IBD pathology. Anti-interleukin-1 therapy may be efficacious in these patients with monogenic very-early-onset IBD.
Assuntos
Doenças Inflamatórias Intestinais , Deficiência de Mevalonato Quinase , Humanos , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/etiologia , Interleucina-1/antagonistas & inibidores , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/tratamento farmacológicoRESUMO
INTRODUCTION: Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disease that can lead to an inflammatory A amyloidosis (AA). METHODS: To study the occurrence of AA in MKD patients we performed a systemic review of the literature and described two novel patients. RESULTS: Amyloidosis occurred in 20 MKD patients, renal impairment being always the revealing symptom of AA. Although an accurate prevalence estimation is not possible since exact MKD prevalence is unknown, AA seems rare in MKD (about 6% if we estimate MKD prevalence at 300 patients worldwide). MVK gene study, available in 18 out of the 20 patients, confirmed two pathogenic mutations in all tested individuals. The most frequent genotype was V377I/I268T (n = 9/18). Retrospective search of clinical signs of MKD established, in all patients carrying MVK pathogenic mutations, a disease onset within the first four years of life. Nephrotic syndrome (n = 15), end-stage renal failure (n = 5) or both (n = 8) pointed out kidney amyloidosis. The youngest patient with renal amyloidosis was a European four-year-old girl previously misdiagnosed with PFAPA syndrome. Five patients died of AA amyloidosis despite the use of a biotherapy for two of them; kidney transplant was performed in nine individuals. Colchicine was not effective in any patient. Anti-interleukin-1 anakinra (n = 8), anti TNF etanercept (n = 7) and anti-interleukin 6 tocilizumab (n = 5) treatments were partially effective. CONCLUSION: Inflammatory A amyloidosis, a rare complication of MKD, can cause death or necessitate kidney transplantation. Early diagnosis and cytokine blocking biotherapy using anti-IL1, anti-TNF or anti-IL6 agents are required to prevent terminal renal failure.
Assuntos
Amiloidose , Deficiência de Mevalonato Quinase , Amiloidose/complicações , Amiloidose/diagnóstico , Pré-Escolar , Feminino , Genótipo , Humanos , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Deficiência de Mevalonato Quinase/tratamento farmacológico , Estudos Retrospectivos , Inibidores do Fator de Necrose TumoralRESUMO
Mevalonate kinase deficiency (MKD) is a rare autosomal recessive autoinflammatory disease caused by mutations in MVK. We report two siblings with MKD, presenting with recurrent febrile illnesses, detected to have compound heterozygous variants in MVK. MKD mimics common pediatric conditions and should be considered as a differential diagnosis.
Assuntos
Febre de Causa Desconhecida/etiologia , Deficiência de Mevalonato Quinase , Pré-Escolar , Hemocromatose , Humanos , Lactente , Masculino , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Fosfotransferases (Aceptor do Grupo Álcool)/genéticaRESUMO
BACKGROUND: This case follows a 14-month-old female, who despite multiple presentations to several physicians, continued to have recurrent febrile episodes with gross motor delay. Her case revealed an often missed diagnosis of Mevalonate Kinase Deficiency, that now has an FDA approved treatment that both reduces recurrence and produces remission. CASE PRESENTATION: A 14-month-old female with a history of gross motor delay, frequent Upper Respiratory Tract infections, and otitis media presented to an urgent care for inconsolability and refusal to bear weight on her right leg. She had recently been treated with amoxicillin for acute otitis media and had developed a diffuse maculopapular rash, without any associated respiratory or gastrointestinal distress that persisted beyond cessation of the antibiotics. The patient presented multiple times to an urgent care over the subsequent week for fussiness, fever, anorexia, lymphadenopathy, with labs concerning for worsening anemia and elevated inflammatory markers. Subsequently, the patient was admitted to the hospital for suspected osteomyelitis versus oncologic process. X-Ray imaging of the patient's lower extremities showed osseous abnormalities inconsistent with infection. A metabolic work-up showed elevated urine mevalonic acid, and follow-up genetic testing was positive for mutations in both copies of her mevalonate kinase gene. This led to the diagnosis of MKD. CONCLUSIONS: Often, episodic presentations require multiple perspectives to reveal the underlying cause. This case illustrates how apparent simple febrile episodes has the potential for more complexity upon further evaluation.
Assuntos
Febre/etiologia , Deficiência de Mevalonato Quinase/diagnóstico , Debilidade Muscular/etiologia , Anticorpos Monoclonais Humanizados/uso terapêutico , Encéfalo/diagnóstico por imagem , Exantema/etiologia , Feminino , Humanos , Lactente , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Imageamento por Ressonância Magnética , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/tratamento farmacológico , Ácido Mevalônico/urinaRESUMO
Systemic inflammation in neonates is attributable to an infection in almost all cases. When inflammation persists, an autoinflammatory disease should be promptly suspected. We report here a case of mevalonate kinase deficiency (MKD) that presented at birth with mild symptoms and signs suggestive for a perinatal infection, together with the uncommon finding of interstitial lung disease. An extensive diagnostic work-up, performed after ineffective antibiotic treatment, demonstrated high levels of mevalonic acid in urine (7024â¯mM/M of creatinine, normal value <0.1). Next-generation sequencing showed a rare c.709Aâ¯>â¯T (p.T237S) homozygous mutation in the MVK gene, consistent with MKD. Treatment with anakinra led to a prompt resolution of symptoms and a sharp drop in serum inflammatory markers. The patient is now six months-old, currently undergoing evaluation for hematopoietic stem-cell transplantation. To our knowledge, this is the first case of MKD presenting within the first week of life with interstitial lung disease.
Assuntos
Doenças Pulmonares Intersticiais/diagnóstico , Deficiência de Mevalonato Quinase/diagnóstico , Sepse Neonatal/diagnóstico , Diagnóstico Diferencial , Feminino , Humanos , Recém-Nascido , Infecções/diagnóstico , Proteína Antagonista do Receptor de Interleucina 1/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Doenças Pulmonares Intersticiais/etiologia , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/tratamento farmacológico , Deficiência de Mevalonato Quinase/genética , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Tomografia Computadorizada por Raios XAssuntos
Amiloidose/etiologia , Febre Familiar do Mediterrâneo/diagnóstico , Falência Renal Crônica/etiologia , Deficiência de Mevalonato Quinase/diagnóstico , Síndrome Nefrótica/etiologia , Adolescente , Amiloidose/sangue , Amiloidose/patologia , Biópsia , Proteína C-Reativa/análise , Diagnóstico Diferencial , Feminino , Testes Genéticos , Humanos , Cariotipagem , Rim/patologia , Falência Renal Crônica/sangue , Falência Renal Crônica/patologia , Deficiência de Mevalonato Quinase/sangue , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/genética , Síndrome Nefrótica/sangue , Síndrome Nefrótica/patologia , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Proteína Amiloide A Sérica/análiseRESUMO
INTRODUCTION: Autoinflammatory diseases can cause irreversible tissue damage due to systemic inflammation. Recently, the Autoinflammatory Disease Damage Index (ADDI) was developed. The ADDI is the first instrument to quantify damage in familial Mediterranean fever, cryopyrin-associated periodic syndromes, mevalonate kinase deficiency and tumour necrosis factor receptor-associated periodic syndrome. The aim of this study was to validate this tool for its intended use in a clinical/research setting. METHODS: The ADDI was scored on paper clinical cases by at least three physicians per case, independently of each other. Face and content validity were assessed by requesting comments on the ADDI. Reliability was tested by calculating the intraclass correlation coefficient (ICC) using an 'observer-nested-within-subject' design. Construct validity was determined by correlating the ADDI score to the Physician Global Assessment (PGA) of damage and disease activity. Redundancy of individual items was determined with Cronbach's alpha. RESULTS: The ADDI was validated on a total of 110 paper clinical cases by 37 experts in autoinflammatory diseases. This yielded an ICC of 0.84 (95% CI 0.78 to 0.89). The ADDI score correlated strongly with PGA-damage (r=0.92, 95% CI 0.88 to 0.95) and was not strongly influenced by disease activity (r=0.395, 95% CI 0.21 to 0.55). After comments from disease experts, some item definitions were refined. The interitem correlation in all different categories was lower than 0.7, indicating that there was no redundancy between individual damage items. CONCLUSION: The ADDI is a reliable and valid instrument to quantify damage in individual patients and can be used to compare disease outcomes in clinical studies.
Assuntos
Doenças Hereditárias Autoinflamatórias/diagnóstico , Índice de Gravidade de Doença , Adolescente , Adulto , Criança , Simulação por Computador , Síndromes Periódicas Associadas à Criopirina/complicações , Síndromes Periódicas Associadas à Criopirina/diagnóstico , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/diagnóstico , Doenças Hereditárias Autoinflamatórias/complicações , Humanos , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Variações Dependentes do Observador , Sistema de Registros , Reprodutibilidade dos Testes , Adulto JovemRESUMO
Mevalonate kinase deficiency is a rare, autosomal recessive, auto-inflammatory disease. This results from mutations in the gene MVK coding for the enzyme mevalonate kinase. This enzyme is involved in cholesterol and isoprenoids synthesis. Depending partially of the residual activity of the mevalonate kinase, the clinical spectrum realizes a continuum which extends from the mild phenotype of the hyperimmunoglobulinemia D and periodic fever syndrome (HIDS) to a lethal form of mevalonic aciduria. The HIDS is characterized by recurrent episodes of fever with an intense inflammatory syndrome, accompanied with lymphadenopathy, abdominal pain, diarrhea, arthralgia, hepatomegaly, splenomegaly and skin rash. The first attack more frequently takes place in the first year of life, even during the neonatal period, where it can be confused with a maternofetal infection. There is furthermore in mevalonate aciduria a psychomotor retardation, a failure to thrive, a cerebellar ataxia, a dysmorphic syndrome and a reduction of the visual acuity. The diagnosis is based on the mevalonic aciduria during febrile attack. Genetics confirm the diagnosis in more than 80 % of the cases. The dosage of IgD, low sensitive and specific, has no interest. There is no reference treatment. The less severe forms can be treated by non-steroidal anti-inflammatory drugs or steroids during febrile attacks. The most severe patients can be treated by biotherapy: antagonists of IL-1, TNF-α and IL-6.
Assuntos
Deficiência de Mevalonato Quinase/diagnóstico , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Diagnóstico Diferencial , Humanos , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/terapia , MutaçãoRESUMO
We experienced a 6-year-old girl diagnosed with mevalonate kinase deficiency (MKD) who had cholestasis, anemia, and elevated inflammatory markers in neonatal period. She was admitted to our hospital because of fever and elevated inflammatory markers at 5 years 11months of age. Without using antibiotics, the fever and the inflammatory markers were spontaneously resolved. MKD was suspected from elevated serum IgD level and the recurrent febrile attacks. The genetic test revealed heterozygous mutation of p.Leu51Phe known as causative gene of MKD and p.Met 282Thr which is the novel mutation. In addition, urinary mevalonate levels increased both in afebrile and febrile periods, and mevalonate kinase activity level was very low. Prednisolone was administered on each attack, and her febrile attack has been controlled well since she was diagnosed with MKD. Fetal edema, cholestasis, anemia, elevation of inflammatory markers in her neonatal period are considered to be complications of MKD. Recurrent fever attacks compromise quality of life in patients with MKD. Children with unexplained cholestasis and anemia in neonatal period, or recurrent fever attacks with elevated inflammatory markers should be examined for MKD.
Assuntos
Colestase/etiologia , Edema/etiologia , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/diagnóstico , Anemia/etiologia , Biomarcadores/sangue , Biomarcadores/urina , Criança , Feminino , Testes Genéticos , Humanos , Imunoglobulina D/sangue , Deficiência de Mevalonato Quinase/tratamento farmacológico , Deficiência de Mevalonato Quinase/genética , Ácido Mevalônico/urina , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Prednisolona/administração & dosagem , Febre Recorrente/etiologia , Resultado do TratamentoAssuntos
Febre Familiar do Mediterrâneo/diagnóstico , Deficiência de Mevalonato Quinase/diagnóstico , Mutação , Fosfotransferases (Aceptor do Grupo Álcool)/genética , Pirina/genética , Criança , Febre Familiar do Mediterrâneo/complicações , Febre Familiar do Mediterrâneo/genética , Marcadores Genéticos , Homozigoto , Humanos , Masculino , Deficiência de Mevalonato Quinase/complicações , Deficiência de Mevalonato Quinase/genéticaRESUMO
Autoinflammatory diseases are characterized by recurrent episodes of fever and localized or systemic inflammation and are caused by monogenic defects of innate immunity. The skin is commonly involved with various manifestations including erysipelas like rash and urticaria. Although vasculitis has been described in many autoinflammatory diseases, it has not been recognized as a characteristic feature of these diseases and autoinflammatory diseases are not listed as an etiology for vasculitis associated with a systemic disease in the 2012 Revised International Chapel Hill Consensus Conference Nomenclature of Vasculitides. We describe herein 3 patients with different autoinflammatory diseases in whom leukocytoclastic vasculitis was one of the major and presenting symptoms. A review of the vast evidence in the literature for vasculitis in the spectrum of autoinflammatory diseases and a suggested pathophysiology is presented. We suggest the term autoinflammatory associated vasculitis to describe vasculitis associated with autoinflammatory diseases. Autoinflammatory diseases should be considered within the differential diagnosis of vasculitis.