Hideo Sasai

Acute cerebellitis associated with rotavirus infection.

BackgroundRotavirus infection is occasionally associated with central nervous system involvement, including cerebellitis. However, the precise clinical sequelae of central nervous system disorders and the usefulness of neuroradiological examination for clinical therapies, such as steroid pulse therapy, have not been clarified.MethodsWe present a case of rotavirus cerebellitis examined by magnetic resonance imaging (MRI), magnetic resonance spectroscopy, and single photon emission computed tomography.ResultsMRI demonstrated abnormal intensities in the right cerebellum on fluid attenuated inversion recovery images and, much more obviously, on diffusion-weighted images, but not on T1- or T2-weighted images. Single photon emission computed tomography showed only mild hypoperfusion in the right cerebellum on the 15th day, while 4 weeks later the image showed remarkably low perfusion in the right cerebellum.ConclusionThe findings of the reported case suggest the importance of performing radiological examinations at early phases of the disease, especially by new modalities such as diffusion weighted imaging, to make timely and appropriate therapeutic decisions.

A transient lesion in the corpus callosum during rotavirus infection.

To the Editor: Fukuda et al. [1] recently reported a case with a transient lesion in the corpus callosum during rotavirus infection. We have just encountered a similar case, and our review suggests the need to reevaluate the spectrum of central nervous system involvement in rotavirus infections. In March 2009, a 1-year-old girl was admitted to our hospital after three incidents of brief tonic convulsions with mild fever, as well as enterocolitis with vomiting and diarrhea for the previous three days. On admission, she was slightly drowsy as a result of diazepam treatment for her convulsions, but she quickly recovered to be fully conscious, engaging in fluent conversation with no evident neurological abnormal findings. Laboratory data including serum sodium (137 mEq/L) and analysis of cerebrospinal fluid were normal. Magnetic resonance imaging on admission showed a marked hyperintensity in the splenium of the corpus callosum on diffusion-weighted image; a slight abnormal was seen on T1or T2-weighted images (Fig 1). The hyperintensity in the splenium disappeared at 6 days after the first imaging (Fig 1). Initial electroencephalography on admission exhibited intermittent spikes and slowwaves in the right occipital region. The patient did not, however, experience any other seizures, and the abnormality was not evident on subsequent electroencephalograms 2 and 6 days after admission. No neurologic complications were evident upon discharge. Rotavirus antigen was detected in

Beta-Ketothiolase Deficiency Resolving Challenges in Diagnosis

Beta-ketothiolase deficiency is an inherited disorder of ketone body metabolism and isoleucine catabolism. It typically manifests as recurrent ketoacidotic episodes with characteristic abnormalitie...

Congenital inner ear malformations without sensorineural hearing loss in children.

Inner ear malformations are frequently found in patients with congenital hearing loss. It has been reported that normal hearing is rare in patients with severe inner ear vestibular malformations. A 9-year-old boy had had complained of recurrent dizziness and disequilibrium for 2 months. Clinical and neuro-otological examinations showed peripheral involvement of the vestibular system, while audiological investigation was normal. High-resolution magnetic resonance imaging, with three-dimensional reconstruction, showed dysplasia of the bilateral lateral semicircular canals (LSCCs). Isolated vestibular malformation might not be as rare as previously thought, and should be examined by imaging of the temporal bone.

Single-nucleotide substitution T to A in the polypyrimidine stretch at the splice acceptor site of intron 9 causes exon 10 skipping in the ACAT1 gene

β‐ketothiolase (T2, gene symbol ACAT1) deficiency is an autosomal recessive disorder, affecting isoleucine and ketone body metabolism. We encountered a patient (GK03) with T2 deficiency whose T2 mRNA level was <10% of the control, but in whom a previous routine cDNA analysis had failed to find any mutations. Genomic PCR‐direct sequencing showed homozygosity for c.941‐9T>A in the polypyrimidine stretch at the splice acceptor site of intron 9 of ACAT1. Initially, we regarded this variant as not being disease‐causing by a method of predicting the effect of splicing using in silico tools. However, based on other findings of exon 10 splicing, we eventually hypothesized that this mutation causes exon 10 skipping.

A Turkish Patient With Succinyl-CoA:3-Oxoacid CoA Transferase Deficiency Mimicking Diabetic Ketoacidosis

Succinyl-CoA:3-oxoacid CoA transferase (SCOT) deficiency is an autosomal recessive disorder of ketone body utilization that is clinically characterized with intermittent ketoacidosis crises. We rep...

Successive MRI Findings of Reversible Cerebral White Matter Lesions in a Patient with Cystathionine β-Synthase Deficiency.

Cystathionine β-synthase (CBS) deficiency, well known as classical homocystinuria, is a rare autosomal recessive inborn error of homocysteine and sulfur metabolism. CBS converts homocysteine to cystathionine. The clinical features of untreated CBS deficiency include myopia, ectopia lentis, mental retardation, skeletal anomalies resembling Marfan syndrome, and thromboembolic events. Cerebral white matter lesions (CWMLs), identified in magnetic resonance imaging (MRI), are related to various clinical conditions including ischemia, inflammation, demyelination, infection, a tumor, and metabolic disorders such as phenylketonuria. The presence of CWMLs is, however, believed to be a very rare condition in CBS-deficient patients. Herein, we report reversible CWMLs associated with hypermethioninemia caused by poor protein restriction and betaine therapy in a 21-year-old male with pyridoxine-nonresponsive CBS deficiency. T2-weighted images (T2WI) and fluid-attenuated inversion-recovery (FLAIR) images showed diffuse high signal intensity in subcortical areas extending to the deep white matter. Diffusion-weighted images (DWI) showed high signal intensity, while apparent diffusion coefficient (ADC) map demonstrated decreased ADC value in the lesions. The course of improvement after correct methionine restriction was successively followed by brain MRI. The CWMLs had regressed at 1 month after restriction, and disappeared after 5 months. ADC values were very low before proper methionine restriction, but normalized after 2 months. Use of betaine in the presence of elevated plasma methionine may increase the risk of reversible CWMLs in some CBS-deficient patients.

Clinical and Mutational Characterizations of Ten Indian Patients with Beta-Ketothiolase Deficiency

Beta-ketothiolase deficiency (mitochondrial acetoacetyl-CoA thiolase (T2) deficiency) is an inherited disease of isoleucine catabolism and ketone body utilization caused by ACAT1 mutations. We identified ten Indian patients who manifested with ketoacidotic episodes of variable severity. The patients showed increased urinary excretion of isoleucine-catabolic intermediates: 2-methyl-3-hydroxybutyrate, 2-methylacetoacetate, and tiglylglycine. Six patients had a favorable outcome, one died, and three developed neurodevelopmental sequela. Mutational analysis revealed a common (p.Met193Arg) and four novel (p.Ile323Thr, p.Ala215Asn, c.1012_1015dup, and c.730+1G>A) ACAT1 mutations. Transient expression analyses of wild-type and mutant cDNA were performed at 30, 37, and 40°C. A p.Ile323Thr mutant T2 was detected with relative enzyme activity and protein amount of 20% and 25%, respectively, compared with wild type at 37°C; it was more prevalent at 30°C but ablated at 40°C. These findings showed that p.Ile323Thr had a significant residual T2 activity with temperature-sensitive instability. Neither residual enzymatic activity nor mutant T2 protein was identified in p.Met193Arg, p.Ala215Asn, and c.1012_1015dup mutations using supernatants; however, these mutant T2 proteins were detected in insoluble pellets by immunoblot analysis. Expression analyses confirmed pathogenicity of these mutations. T2 deficiency has a likely high incidence in India and p.Met193Arg may be a common mutation in the Indian population.

Effectiveness of Medium-Chain Triglyceride Oil Therapy in Two Japanese Citrin-Deficient Siblings: Evaluation Using Oral Glucose Tolerance Tests

Citrin deficiency, an inherited defect of the liver-type mitochondrial aspartate/glutamate carrier isoform (citrin), may cause impairment of glycolysis because of an increase in the cytosolic NADH/NAD+ ratio. We report a Japanese boy whose main complaint was recurrent hypoglycemic episodes. He was suspected as having citrin deficiency because of his peculiar preference for protein- and fat-rich food. His young sister also had a similar food preference. Both siblings were diagnosed with citrin deficiency by genetic analysis. The brother and sister underwent an oral glucose tolerance test (OGTT) at 10 and 7 yr of age, respectively. Blood glucose, ammonia, lactic acid, pyruvic acid, and insulin levels were monitored before starting the test, and then every 30 min. During this test, they maintained blood glucose levels until 180 min. At 210 min, they experienced vomiting, feeling ill, and decreased blood glucose levels (2.9 and 2.8 mmol/l in the brother and sister, respectively). The sister and brother recovered uneventfully by intravenous glucose injection. In a second OGTT, 4 months after medium-chain triglyceride (MCT) oil supplementation, they had no major symptoms and normal glucose levels were maintained, even after 240 min. Additionally, after MCT oil therapy, their food preference slightly changed as they started eating more carbohydrates. Our OGTT data suggest excess carbohydrate intake has adverse consequences in patients with citrin deficiency, including hypoglycemia after a few hours. MCT oil therapy may be effective in preventing such hypoglycemia and improving metabolic derangement, even during the so-called apparently healthy period.

Successful treatment of pediatric immune thrombocytopenic purpura associated with ulcerative colitis.

A large number of extraintestinal manifestations of chronic inflammatory bowel disease (IBD) has been reported. They are seen in approximately 25% of patients with chronic IBD, with a significantly higher proportion in patients with Crohn’s disease. Several hematological abnormalities, often autoimmune hemolytic anemia, have also been described in association with chronic IBD. Immune thrombocytopenic purpura (ITP), also referred to as idiopathic thrombocytopenic purpura, has been sporadically reported in individuals with chronic IBD, mostly ulcerative colitis (UC). ITP is a destructive thrombocytopenia caused by autoantibodies against platelet glycoproteins (GP), and UC is a chronic IBD of unknown etiology. It is not yet conclusive whether these diseases are involved in each other’s pathogenesis, though the treatment of UC is known to be enough to treat ITP. Herein, we describe a 12-year-old girl with ITP associated with UC who also had anemia, hematochezia, and purpura. Her anemia was considered to be caused by intestinal hemorrhaging from the UC, and purpura was thought to be caused by ITP. She was treated with prednisolone (PSL) and 5-aminosalicylic acid (5-ASA), and the diseases now remain under control.