RESUMEN
A 37-year-old Han Chinese man, with a history of severe ulcerative colitis with incomplete response to oral glucocorticoids, was commenced on azathioprine [AZA] 200mg once a day. His pre-treatment thiopurine S-methyltransferase [TPMT] levels were in the normal range. Eleven days later he developed symptoms of stomatitis and gingivitis. Chinese herbal medications were taken in an attempt to treat these symptoms. He presented to the emergency department with this, with normal vital signs. A full blood count five days post-onset of symptoms showed pancytopenia with an absolute neutrophil count [ANC] of 0.0x10(9)/l, C-reactive protein was 120 mg/L. Initial chest radiograph, urinalysis and peripheral blood cultures were unremarkable and he was commenced on broad spectrum antibiotics and granulocyte colony stimulating factor [G-CSF]. He remained an inpatient under the gastroenterology team for 16 days and developed infectious complications of herpes simplex stomatitis, oral candidiasis, dental abscess, and scalp abscess. On day 16 his ANC recovered to 1.0x10(9)/L and was discharged from the hospital. He underwent nudix hydrolase 15 [NUDT15] genotyping and was found to have homozygosity for the variant NUDT15:c.415C>T. This case demonstrates the importance of pre-treatment testing for NUDT15 genetic variants, to predict the risk of severe leucopaenia, particularly in a patient of East Asian ethnicity.
Asunto(s)
Leucopenia , Estomatitis , Absceso , Adulto , Azatioprina/efectos adversos , Azatioprina/metabolismo , Humanos , Leucopenia/inducido químicamente , Leucopenia/diagnóstico , Leucopenia/genética , Masculino , Nueva Zelanda , Pirofosfatasas/genéticaRESUMEN
Folate and vitamin B(12) metabolism are essential for de novo purine synthesis, and several defects in these pathways have been associated with immunodeficiency. Here we describe the occurrence of severe combined immunodeficiency (SCID) with megaloblastic anemia, leukopenia, atypical hemolytic uremic syndrome, and neurologic abnormalities in which hydroxocobalamin and folate therapy provided partial immune reconstitution. Whole exome sequencing identified compound heterozygous mutations in the MTHFD1 gene, which encodes a trifunctional protein essential for processing of single-carbon folate derivatives. We now report the immunologic details of this novel genetic cause of SCID and the response to targeted metabolic supplementation therapies. This finding expands the known metabolic causes of SCID and presents an important diagnostic consideration given the positive impact of therapy.
Asunto(s)
Análisis Mutacional de ADN , Metilenotetrahidrofolato Deshidrogenasa (NADP)/genética , Inmunodeficiencia Combinada Grave/genética , 3-Hidroxiacil-CoA Deshidrogenasas/deficiencia , 3-Hidroxiacil-CoA Deshidrogenasas/genética , Anemia Megaloblástica/diagnóstico , Anemia Megaloblástica/tratamiento farmacológico , Anemia Megaloblástica/genética , Examen de la Médula Ósea , Cardiomiopatías/diagnóstico , Cardiomiopatías/tratamiento farmacológico , Cardiomiopatías/genética , Terapia Combinada , Combinación de Medicamentos , Quimioterapia Combinada , Exoma/genética , Femenino , Tamización de Portadores Genéticos , Humanos , Hidroxocobalamina/uso terapéutico , Inmunización Pasiva , Lactante , Recién Nacido , Leucopenia/diagnóstico , Leucopenia/tratamiento farmacológico , Leucopenia/genética , Errores Innatos del Metabolismo Lipídico/diagnóstico , Errores Innatos del Metabolismo Lipídico/tratamiento farmacológico , Errores Innatos del Metabolismo Lipídico/genética , Antígenos de Histocompatibilidad Menor , Miopatías Mitocondriales , Proteína Trifuncional Mitocondrial/deficiencia , Enfermedades del Sistema Nervioso , Infecciones Oportunistas/diagnóstico , Infecciones Oportunistas/tratamiento farmacológico , Infecciones Oportunistas/genética , Enfermedades del Sistema Nervioso Periférico/diagnóstico , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/genética , Neumonía por Pneumocystis/diagnóstico , Neumonía por Pneumocystis/tratamiento farmacológico , Neumonía por Pneumocystis/genética , Retinitis Pigmentosa/diagnóstico , Retinitis Pigmentosa/tratamiento farmacológico , Retinitis Pigmentosa/genética , Rabdomiólisis , Análisis de Secuencia de ADN , Inmunodeficiencia Combinada Grave/diagnóstico , Inmunodeficiencia Combinada Grave/tratamiento farmacológico , Sulfadoxina/uso terapéutico , Trimetoprim/uso terapéutico , Vitamina B 12/uso terapéuticoRESUMEN
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Asunto(s)
Humanos , Leucopenia/complicaciones , Leucopenia/diagnóstico , Paroxetina/efectos adversos , Paroxetina/uso terapéutico , 26467 , 26467RESUMEN
Adrenalin test in 69% of examinees who had faced long exposure to oil products revealed redistribution leukopenia caused by compromised neurovascular regulation. Toxic origin of the leukopenia in 10.4% of workers was supported not only by the adrenalin test but also by pyrogenal one which proved exhaustion of granulocyte reserve in the bone marrow.