ABSTRACT
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.
Subject(s)
Leukopenia , Stomatitis , Abscess , Adult , Azathioprine/adverse effects , Azathioprine/metabolism , Humans , Leukopenia/chemically induced , Leukopenia/diagnosis , Leukopenia/genetics , Male , New Zealand , Pyrophosphatases/geneticsABSTRACT
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.
Subject(s)
DNA Mutational Analysis , Methylenetetrahydrofolate Dehydrogenase (NADP)/genetics , Severe Combined Immunodeficiency/genetics , 3-Hydroxyacyl CoA Dehydrogenases/deficiency , 3-Hydroxyacyl CoA Dehydrogenases/genetics , Anemia, Megaloblastic/diagnosis , Anemia, Megaloblastic/drug therapy , Anemia, Megaloblastic/genetics , Bone Marrow Examination , Cardiomyopathies/diagnosis , Cardiomyopathies/drug therapy , Cardiomyopathies/genetics , Combined Modality Therapy , Drug Combinations , Drug Therapy, Combination , Exome/genetics , Female , Genetic Carrier Screening , Humans , Hydroxocobalamin/therapeutic use , Immunization, Passive , Infant , Infant, Newborn , Leukopenia/diagnosis , Leukopenia/drug therapy , Leukopenia/genetics , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/drug therapy , Lipid Metabolism, Inborn Errors/genetics , Minor Histocompatibility Antigens , Mitochondrial Myopathies , Mitochondrial Trifunctional Protein/deficiency , Nervous System Diseases , Opportunistic Infections/diagnosis , Opportunistic Infections/drug therapy , Opportunistic Infections/genetics , Peripheral Nervous System Diseases/diagnosis , Peripheral Nervous System Diseases/drug therapy , Peripheral Nervous System Diseases/genetics , Pneumonia, Pneumocystis/diagnosis , Pneumonia, Pneumocystis/drug therapy , Pneumonia, Pneumocystis/genetics , Retinitis Pigmentosa/diagnosis , Retinitis Pigmentosa/drug therapy , Retinitis Pigmentosa/genetics , Rhabdomyolysis , Sequence Analysis, DNA , Severe Combined Immunodeficiency/diagnosis , Severe Combined Immunodeficiency/drug therapy , Sulfadoxine/therapeutic use , Trimethoprim/therapeutic use , Vitamin B 12/therapeutic useABSTRACT
No disponible
Subject(s)
Humans , Leukopenia/complications , Leukopenia/diagnosis , Paroxetine/adverse effects , Paroxetine/therapeutic use , 26467 , 26467ABSTRACT
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.