RESUMO
INTRODUCTION: Late-onset multiple acyl-CoA dehydrogenase deficiency (MADD) is a rare, treatable, beta-oxidation disorder responsible for neuromuscular symptoms in adults. This case series describes the clinical and biochemical features of 13 French patients with late-onset MADD. METHODS AND RESULTS: Thirteen ambulant patients (eight women, five men), with a median age at onset of 27 years, initially experienced exercise intolerance (n=9), isolated muscle weakness (n=1) and a multisystemic pattern with either central nervous system or hepatic dysfunction (n=3). During the worsening period, moderate rhabdomyolysis (n=5), a pseudomyasthenic pattern (n=5) and acute respiratory failure (n=1) have been observed. Weakness typically affected the proximal limbs and axial muscles, and there was sometimes facial asymmetry (n=3). Moderate respiratory insufficiency was noted in one case. Median baseline creatine kinase was 190IU/L. Lactacidemia was sometimes moderately increased at rest (3/10) and after exercise (1/3). The acylcarnitine profile was characteristic, with increases in all chain-length acylcarnitine species. Electromyography revealed a myogenic pattern, while muscle biopsy showed lipidosis, sometimes with COX-negative fibers (n=2). The mitochondrial respiratory chain was impaired in five cases, with coenzyme Q10 decreased in two cases. All patients harbored mutations in the ETFDH gene (four homozygous, seven compound heterozygous, two single heterozygous), with nine previously unidentified mutations. All patients were good responders to medical treatment, but exercise intolerance and/or muscular weakness persisted in 11 of them. CONCLUSION: Late-onset forms of MADD may present as atypical beta-oxidation disorders. Acylcarnitine profiling and muscle biopsy remain the most decisive investigations for assessing the diagnosis. These tests should thus probably be performed more widely, particularly in unexplained cases of neuromuscular and multisystemic disorders.
Assuntos
Erros Inatos do Metabolismo Lipídico/enzimologia , Erros Inatos do Metabolismo Lipídico/terapia , Deficiência Múltipla de Acil Coenzima A Desidrogenase/complicações , Deficiência Múltipla de Acil Coenzima A Desidrogenase/genética , Doenças Neuromusculares/enzimologia , Doenças Neuromusculares/terapia , Adulto , Idade de Início , Biópsia , Carnitina/análogos & derivados , Carnitina/metabolismo , Eletromiografia , Flavoproteínas Transferidoras de Elétrons/genética , Exercício Físico , Feminino , França , Humanos , Proteínas Ferro-Enxofre/genética , Erros Inatos do Metabolismo Lipídico/genética , Masculino , Pessoa de Meia-Idade , Músculo Esquelético/enzimologia , Músculo Esquelético/patologia , Mutação/genética , Doenças Neuromusculares/genética , Oxirredução , Oxirredutases atuantes sobre Doadores de Grupo CH-NH/genética , Rabdomiólise/etiologia , Adulto JovemRESUMO
BACKGROUND: Mucopolysaccharidosis type I-Hurler syndrome (MPSI-H) is a lysosomal storage disease characterized by severe physical symptoms and cognitive decline. Early treatment with hematopoietic cell transplant (HSCT) is critical to the survival of these patients. While survival rates and short-term outcomes are known to be improved by HSCT, the long-term cognitive, adaptive and psychosocial functional outcomes of children with (MPSI-H) post-HSCT are not well documented. This manuscript focuses on retrospective long-term follow-up (7-33 years) of 25 MPSI-H patients, transplanted between 1986 and 2011. RESULTS: The median age at transplantation was 21 months (range 12-57 months). Except for one death, all successfully transplanted MPSI-H patients surviving at least 1 year after HSCT are alive to-date, with a median age of 21 years (range 8-36 years) at the last follow-up evaluation. A majority of HSCT grafts were bone marrow transplants (BMT), resulting in durable full chimerism in 18 (72%). Pre-HSCT, the onset of first symptoms occurred very early, at a median age of 3 months (range birth-16 months). The most prevalent symptoms before MPSI-H diagnosis involved progressive dysostosis multiplex; almost all patients suffered from hip dysplasia and thoracolumbar spine Kyphosis. Despite HSCT, considerable residual disease burden and ensuing corrective surgical interventions were observed in all, and at every decade of follow-up post HSCT. Late-onset psychiatric manifestations were significant (n = 17 patients; 68%), including depression in 13 patients at a median onset age of 18 years (range 13-31 years), hyperactivity and attention deficit disorder (n = 4), and multiple acute psychotic episodes (APE), independent of depression observed (n = 3) at a median onset age of 18 years (range 17-31 years). The adult Welscher Intelligence Scale results (n = 16) were heterogenous across the four scale dimensions; overall lower scores were observed on both working memory index (median WMI = 69.5) and processing speed index (median PSI = 65), whereas verbal comprehension index (median VCI = 79) and perceptual reasoning index (median PRI = 74) were higher. CONCLUSION: With advanced treatment options, MPSI-H are living into 3rd and 4th decades of life, however not disease free and with poor adaptation. Residual disease (loss of mobility, limited gross and fine motor skills; low cognitive ability; suboptimal cardiopulmonary function, vision and hearing) negatively impacts the quality of life and psychosocial functioning of affected individuals.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Mucopolissacaridose I , Adolescente , Adulto , Criança , Pré-Escolar , Efeitos Psicossociais da Doença , Humanos , Lactente , Mucopolissacaridose I/terapia , Qualidade de Vida , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Mutations in the RMND1 gene, causing defects in the mitochondrial respiratory chain, result in a very heterozygous phenotype. Currently there are 36 cases reported in the literature. We report two siblings from a non-consanguineous family who were severely affected by a compound heterozygous RMND1 mutation that had not been described previously and were treated differently for their end-stage renal disease. We summarize all previous published cases and focus on the importance of extrarenal comorbidities in the context of therapeutic decision making (renal replacement therapy) and its ethical relevance.
Assuntos
Proteínas de Ciclo Celular/genética , Tomada de Decisão Clínica/ética , Falência Renal Crônica/genética , Doenças Mitocondriais/genética , Irmãos , Evolução Fatal , Feminino , Heterozigoto , Humanos , Falência Renal Crônica/diagnóstico , Falência Renal Crônica/terapia , Masculino , Doenças Mitocondriais/diagnóstico , Doenças Mitocondriais/terapia , Mutação , Fenótipo , Índice de Gravidade de DoençaRESUMO
Inherited metabolic diseases (IMD) form a heterogeneous group of genetic disorders that surface primarily during childhood and result in significant morbidity and mortality. A prevalence of 1 in 2500-5000 live births is often reported. The transfer of adolescents from pediatric care to adult health facilities is often difficult for patients and their families and can lead to a breakdown in medical follow-up and therefore serious complications. Existing recommendations for the successful transition of patients with chronic disorders do not specifically address patients with IMDs associated with dietary treatment. Here, the French network for rare inherited metabolic diseases (G2M) presents its reflections and recommendations for a successful transition. Preparations for the transfer must be made well in advance. The transfer must aim for adolescents gaining autonomy by making them responsible and providing them with the knowledge that will enable them to manage their care themselves, know how to react appropriately if there is any change in their condition, and move comfortably within the adult healthcare system. This requires the active participation of the patient, his or her family, and pediatric and adult care teams. It involves multidisciplinary management plus the production and maintenance of an educational therapy program. Finally, the identification of physicians and dietitians trained in IMDs, relevant subspecialists, and even expert patients could improve the continuum of complete and appropriate care for these patients within adult medicine.
RESUMO
Gaucher disease is well-known in adult patients and must be regarded as a pediatric disease, two thirds of the patients manifesting before the age of 20. Three clinical forms have been defined based on the presence of neurological involvement. Gaucher disease type 1, without neurological signs, generally begins before the five years age with splenomegaly as the main symptom. The bone crises are more frequent than in adulthood. Gaucher disease type 2 or acute neuronopathic form begins between three and six months and do not have any treatment. Type 3 or chronic neuronopathic form appears like a type 1 with progressive horizontal saccade-initiation failure and developmental delay. Onset in childhood is predictive of a severe and progressive phenotype. The presence of neurological symptoms induces important consequences for treatment, prognosis and genetic counselling.
Assuntos
Doença de Gaucher , Adolescente , Adulto , Fatores Etários , Analgésicos/uso terapêutico , Criança , Pré-Escolar , Difosfonatos/uso terapêutico , Progressão da Doença , Eletroencefalografia , Doença de Gaucher/classificação , Doença de Gaucher/diagnóstico , Doença de Gaucher/epidemiologia , Doença de Gaucher/genética , Doença de Gaucher/terapia , Aconselhamento Genético , Glucosilceramidase/administração & dosagem , Glucosilceramidase/uso terapêutico , Humanos , Incidência , Lactente , Recém-Nascido , Fenótipo , Prognóstico , Esplenomegalia/etiologia , Fatores de TempoRESUMO
PURPOSE: To describe ocular manifestations in Fabry disease and compare them to other organ involvement in this disease. PATIENTS AND METHODS: Ten patients were included in a clinical trial, all of whom had specialized investigations in ophthalmology, cardiology, nephrology and dermatology. RESULTS: All the patients presented with ocular damage, some of which were rather characteristic of this disease, such as cornea verticillata and spoke-like cataract. However, such anomalies were not responsible for any visual acuity changes in most patients. Some patients had renal or cardiovascular damage at early stages of the disease. We therefore tried to establish a correlation between the severity of such involvement and ocular damage. CONCLUSION: Many ocular manifestations are frequently observed that should suggest a diagnosis of Fabry disease. However, there is no clear relationship between the presentation of the systemic cardiac and renal manifestations of the disease and the presence of ocular abnormalities.
Assuntos
Oftalmopatias/etiologia , Doença de Fabry/complicações , Doença de Fabry/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We report the cases of 2 boys and 1 girl suffering from Netherton syndrome. Both boys presented with a non-bullous congenital erythroderma and were diagnosed early as Netherton syndrome with hair biopsies. Both had severe failure to thrive, signs of atopy, several episodes of bacterial infection, and rickets (with a high blood level of vitamin D in the first boy, and vitamin D deficiency in the second). In the third case, the pilar abnormality appeared at the age of 3 years. The girl had ichtyosis linearis circumflexa, failure to thrive and severe constipation. Netherton syndrome is a rare disorder characterized by severe ichtyosis, signs of atopy, immune deficiency and failure to thrive. The disease is severe and comprises many complications in early infancy. It is due to a genetic disorder of recessive autosomal transmission, and the gene, SPINK5, is located in the chromosome 5. Prenatal diagnosis is possible. Two of our patients had rickets, which has never been described in such patients population.
Assuntos
Insuficiência de Crescimento/patologia , Cabelo/anormalidades , Eritrodermia Ictiosiforme Congênita/patologia , Síndromes de Imunodeficiência/patologia , Raquitismo/patologia , Proteínas de Transporte/genética , Pré-Escolar , Cromossomos Humanos Par 5/genética , Feminino , Humanos , Eritrodermia Ictiosiforme Congênita/genética , Lactente , Masculino , Proteínas Secretadas Inibidoras de Proteinases , Inibidor de Serinopeptidase do Tipo Kazal 5 , Inibidores de Serina Proteinase/genética , SíndromeRESUMO
We report the case of an elderly woman with severe dysautonomic orthostatic hypotension in whom a deficit in dopamine B hydroxylase has been established. In the literature, such a deficit has been described in six young adults with long standing symptoms of postural hypotension. This enzyme catalyses the conversion of dopamine to noradrenaline. In our elderly patient, noradrenaline and adrenaline were undetectable in the plasma, but plasma dopamine was detectable. Treatment with the synthetic amino acid, DL-threo-dihydroxyphenylserine, which is converted to noradrenaline by dopa-decarboxylase, resulted in a significant increase in blood pressure. The mechanism of this acquired deficit is not elucidated.
Assuntos
Doenças do Sistema Nervoso Autônomo/etiologia , Dopamina beta-Hidroxilase/deficiência , Hipotensão Ortostática/etiologia , Doenças Metabólicas/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Bioensaio , Pressão Sanguínea/efeitos dos fármacos , Dopamina/sangue , Dopamina beta-Hidroxilase/fisiologia , Droxidopa/administração & dosagem , Droxidopa/farmacologia , Droxidopa/uso terapêutico , Epinefrina/sangue , Feminino , Humanos , Doenças Metabólicas/complicações , Doenças Metabólicas/tratamento farmacológico , Norepinefrina/sangueRESUMO
Eyelid localisation of non-Hodgkin's lymphoma is rare, and even more so when it is bilateral. We report a 58 year-old man who presented with an eyelid localisation of lymphoplasmacytoid lymphoma. The initial treatment was chemotherapy with good improvement but the relapse lead us to give radiotherapy with no further relapse 20 months later. Radiotherapy is the current treatment of localised eyelid lymphomas with excellent results. The prognosis is related to the initial staging and the 10-year survival rate is close to 80%.
Assuntos
Neoplasias Palpebrais/terapia , Leucemia Linfocítica Crônica de Células B/terapia , Terapia Combinada , Neoplasias Palpebrais/tratamento farmacológico , Neoplasias Palpebrais/radioterapia , Humanos , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/radioterapia , Masculino , Pessoa de Meia-Idade , Indução de Remissão/métodosRESUMO
We report three cases of intoxication with anticoagulant rodenticides. This intoxication leads to prolonged hypocoagulability despite vitamin K therapy. In our patients, the side effect was present for 2 to 3 months.
Assuntos
Hipoprotrombinemias/induzido quimicamente , Rodenticidas/intoxicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de TempoRESUMO
78 consecutive cases of PCP have been analysed: 59 (75.6%) cases were associated with HIV infection and 19 (24.4%) cases were associated with solid tumors and hematologic malignancies at advanced stage of the disease and renal transplantation. It could suggest primary prevention for such patients.
Assuntos
Hospedeiro Imunocomprometido , Pneumonia por Pneumocystis/imunologia , França , Hospitais Universitários , HumanosRESUMO
OBJECTIVE: This study was aimed at determining the diagnostic value of conventional laboratory tests regarding the iron status and serum transferrin receptor in hospitalized patients. METHODS: Patients who had to undergo bone marrow aspirate examination were included in this 8-month prospective study. Iron deficiency was defined as the absence of stainable iron on bone marrow examination. Patients with stainable iron were included in the control group. The higher value of diagnostic efficacy determined the cut-off value for each parameter of the iron status. RESULTS: Twenty-one patients (17 females, four males) (mean age: 52 years) with iron deficiency and 33 control subjects (20 females, 13 males) (mean age: 60 years) were included in the study. The ratio serum transferrin receptor/serum ferritin had the best diagnostic efficiency (78%) with a sensitivity of 81% and a specificity of 97%. Serum ferritin alone with a cut-off value of 60 micrograms/L had the same specificity (97%) but a lower sensitivity (76%). The diagnostic value of all other analyzed tests was below 66% (transferrin alone, mean corpuscular volume, transferrin saturation, iron, serum transferrin receptor alone, red cell distribution width). CONCLUSION: Among in-patients, ferritin remains the first intention test to diagnose iron deficiency, but the cut-off value should be increased (60 micrograms/L in this study). The ratio "serum transferrin receptor to serum ferritin" provides the highest specificity with a higher cost and should be used only in doubtful cases.
Assuntos
Anemia Ferropriva/sangue , Anemia Ferropriva/diagnóstico , Ferritinas/sangue , Receptores da Transferrina/sangue , Anemia Ferropriva/patologia , Exame de Medula Óssea , Estudos de Casos e Controles , Custos e Análise de Custo , Índices de Eritrócitos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Sensibilidade e Especificidade , Albumina Sérica/análiseRESUMO
UNLABELLED: In this study, two cases have been reported of idiopathic plantar hidradenitis, an uncommon dermatological pathology with a spontaneous favorable outcome. OBSERVATIONS: Two children aged 12 and 14 years presented with a painful papulo-nodular plantar rash with major functional impairment. The diagnosis of idiopathic plantar hidradenitis was considered, and then confirmed in one case by plantar biopsy. Non-steroidal antiinflammatory drugs, associated with paracetamol in one case were administered. The symptoms disappeared spontaneously within a few days in both cases, without any recurrence. CONCLUSION: A knowledge of the symptoms connected with plantar hidradenitis in the child allows a rapid diagnosis to be made without hospitalization or further medical examination. Analgesic treatment and rest seem to be the only useful approaches. Biopsy to investigate eccrine gland infiltration by neutrophils can only be proposed in the case of an abnormally prolonged duration or an atypical presentation of this pathology.
Assuntos
Dermatoses do Pé/diagnóstico , Hidradenite/diagnóstico , Acetaminofen/uso terapêutico , Atividades Cotidianas , Adolescente , Analgésicos não Narcóticos/uso terapêutico , Anti-Inflamatórios não Esteroides/uso terapêutico , Biópsia , Criança , Diagnóstico Diferencial , Feminino , Dermatoses do Pé/classificação , Dermatoses do Pé/complicações , Dermatoses do Pé/tratamento farmacológico , Hidradenite/classificação , Hidradenite/complicações , Hidradenite/tratamento farmacológico , Humanos , Masculino , Dor/etiologia , DescansoRESUMO
UNLABELLED: Behçet's disease can be revealed by neurologic signs. CASE REPORTS: We report two pediatric cases of Behçet's disease which initially presented with cerebral venous thrombosis. Glucocorticoïds, associated with anticoagulant treatment allowed a rapid recovery. One of the children presented three years later a thrombotic recurrence. CONCLUSION: A cerebral venous thrombosis may reveal Behçet's disease.
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Síndrome de Behçet/tratamento farmacológico , Glucocorticoides/uso terapêutico , Trombose Intracraniana/etiologia , Trombose Venosa/etiologia , Adolescente , Síndrome de Behçet/complicações , Síndrome de Behçet/diagnóstico , Criança , Diagnóstico Diferencial , Humanos , Masculino , Resultado do TratamentoRESUMO
OBJECTIVES: Cold agglutinins and cryoglobulins are uncommon in the same patient as observed in our case. CASE REPORT: A 74-year-old patient suffered repeated episodes of hemolytic anemia for one year and had hepatitis C anti-virus antibodies. Mixed cryoglobulinemia was found at levels which increased during episodes of acute hemolysis in addition to anti-I cold agglutinins. Two-dimensional electrophoresis revealed identical oligoclonal cold agglutinins and cryoglobulins. DISCUSSION: Unlike mixed cryoglobulinemia, cold agglutinins are not known to occur subsequent to hepatitis C infection. The identical immunoglobulins observed in our patient suggest a common origin. Chronic anti-I cold oligoclonal agglutinins are rarely observed and could be an intermediary step towards monoclonal lymphopathy as has been described in prolonged hepatitis C infection.
Assuntos
Aglutininas/análise , Crioglobulinemia/complicações , Hepatite C/complicações , Idoso , Anemia Hemolítica/complicações , Anemia Hemolítica/imunologia , Temperatura Baixa , Crioglobulinemia/imunologia , Crioglobulinas/análise , Feminino , Hepatite C/imunologia , Humanos , Fatores de TempoAssuntos
Raquitismo , Deficiência de Vitamina D , Vitamina D/uso terapêutico , Densidade Óssea/fisiologia , Cálcio/farmacologia , Cálcio/uso terapêutico , Criança , Pré-Escolar , Diagnóstico Diferencial , Humanos , Lactente , Recém-Nascido , Raquitismo/diagnóstico , Raquitismo/fisiopatologia , Raquitismo/terapia , Vitamina D/farmacologia , Deficiência de Vitamina D/diagnóstico , Deficiência de Vitamina D/fisiopatologia , Deficiência de Vitamina D/terapiaRESUMO
Fabry disease is a rare lysosomal storage disorder resulting from deficient activity of alpha-galactosidase A and subsequent pathological accumulation of glycosphingolipids throughout the body. Traditionally, Fabry disease was managed symptomatically, but the introduction of enzyme replacement therapies (ERTs) (agalsidase beta (Fabrazyme); agalsidase alfa (Replagal)) has transformed treatment of this disorder. Clinical studies of both compounds have demonstrated clearance of glycosphingolipds from key tissues. To explore whether substrate clearance translates into clinical benefit, a retrospective survey of 17 patients (mean age 34.7 years) treated with agalsidase beta (1 mg/kg every 2 weeks) was undertaken, using an eight-item retrospective questionnaire developed specifically to assess the effect of ERT on the symptoms of Fabry disease. Pain severity, heat tolerance, physical activity, fatigue and psychological status were scored using a 10-point visual analogue scale (e.g. for pain severity: 1=none, 10=strong). Answers to all other questions were quantitative. Changes in mean scores were 4.69 to 2.25 (p =0.012) for pain severity; 4.38 to 2.21 (p =0.019) for number of pain crises per month; 8.69 to 2.98 (p =0.097) for duration of pain crises in hours; 2.76 to 5.76 (p =0.002) for heat tolerance; 3.28 to 2.51 (p =0.058) for bowel movements per day; 2.47 to 4.47 (p =0.007) for frequency of physical activity; 5.53 to 3.71 (p =0.046) for fatigue, and 5.82 to 8.12 (p =0.005) for psychological status. All patients improved in at least one aspect, although the degree of improvement across patients and aspects varied widely; reasons for this remain unclear. Despite the inherent bias involved in retrospective questionnaires, we believe that the findings are encouraging. A prospective version of the questionnaire is currently under validation.