ABSTRACT
Carbamoylphosphate synthetase I deficiency (CPS1D) is a urea-cycle disorder characterized by episodes of life-threatening hyperammonemia. Correct diagnosis is crucial for patient management, but is difficult to make from clinical presentation and conventional laboratory tests alone. Enzymatic or genetic diagnoses have also been hampered by difficult access to the appropriate organ and the large size of the gene (38 exons). In this study, in order to address this diagnostic dilemma, we performed the largest mutational and clinical analyses of this disorder to date in Japan. Mutations in CPS1 were identified in 16 of 18 patients with a clinical diagnosis of CPS1D. In total, 25 different mutations were identified, of which 19 were novel. Interestingly, in contrast to previous reports suggesting an extremely diverse mutational spectrum, 31.8% of the mutations identified in Japanese were common to more than one family. We also identified two common polymorphisms that might be useful for simple linkage analysis in prenatal diagnosis. The accumulated clinical data will also help to reveal the clinical presentation of this rare disorder in Japan.
Subject(s)
Carbamoyl-Phosphate Synthase (Ammonia)/genetics , Carbamoyl-Phosphate Synthase I Deficiency Disease/diagnosis , Carbamoyl-Phosphate Synthase I Deficiency Disease/genetics , Asian People/genetics , Carbamoyl-Phosphate Synthase (Ammonia)/chemistry , DNA Mutational Analysis , Female , Humans , Japan , Male , Mutation , Polymorphism, GeneticABSTRACT
A 57-year-old woman had undergone surgery for meningioma. After the surgery, she suffered from repeated fever and headache. One year after surgery, she was admitted to our hospital for further examination. Cerebro-spinal fluid (CSF) findings indicated bacterial meningitis infection. Germ culture, acid-fast bacterium culture, PCR for mycobacteriosis and cryptococcus antigens as well as cytological examination of CSF were checked repeatedly. However, all examinations were negative and etiology was unknown. We treated with many anti-bacterial, anti-fungal and anti-tubercular drugs, but CSF findings were not improved. We repeated CSF examination and finally Mycobacterium fortuitum (M. fortuitum) was isolated. Clarithromycin (CAM) was started for M. fortuitum meningitis. After drug sensitivity testing, levofloxacin (LVFX), which was effective against M. fortuitum, was added to CAM, after which clinical and CSF findings improved dramatically. M. fortuitum rarely causes CNS infection. Several English literatures on M. fortuitum meningitis after traumatic injury and surgery have been published. Its CSF findings distinctly resemble those of bacterial meningitis, but are resistant to the usual antituberculosis drugs. We reported a case of M. fortuitum meningitis associated with surgery for meningioma.
