Cholesterol ester storage disease with a novel LIPA mutation (L264P) that presented massive hepatomegaly: A case report.

Cholesterol ester storage disease (CESD) is an autosomal recessive disorder caused by deficient lysosomal acid lipase (LAL) activity, resulting in cholesteryl ester (CE) accumulation. CESD patients have liver disease associated with mixed dyslipidemia leading to liver failure. We here report the case of an 11-year-old male CESD patient with a novel mutation who had the chief complaint of massive hepatomegaly. The patient's liver reached to his pelvis, and his spleen was 2 cm below the costal margin. The patient had elevated serum liver enzymes and mixed dyslipidemia. The liver biopsy tissue showed characteristic CESD pathology, which included microvesicular steatosis, mild fibrosis and foamy macrophages. Electron microscopy showed a remnant cleft of CE crystals, and dried blood spot testing showed reduced LAL activity. We identified compound heterozygous mutations in the LIPA gene in this patient, namely, c.607G>C and c.791T>C. The former mutation was previously reported only in a Japanese patient, whereas the latter mutation is novel. The findings of this study suggest that LIPA gene mutations in Japanese CESD patients are different from those in Western patients. Although CESD is rare, it is likely that many patients are unrecognized or misdiagnosed, and thus the possibility of CESD should be considered in patients with hepatosplenomegaly and dyslipidemia.

Evaporative light-scattering analysis of sulforaphane in broccoli samples: Quality of broccoli products regarding sulforaphane contents.

Broccoli sulforaphane has received attention as a possible anticarcinogen. Sulforaphane analysis is difficult due to the lack of a chromophore for spectrometric detection. Hence, we developed a method for determining sulforaphane by using high-performance liquid chromatography (HPLC) coupled with an evaporative light-scattering detector (ELSD). Sulforaphane was extracted from acid-hydrolyzed broccoli samples, followed by solid-phase extraction and reversed-phase HPLC. Sulforaphane was detected by ELSD and concurrently identified by electrospray ionization time-of-flight mass spectrometry. The recovery of sulforaphane from broccoli samples was above 95%. The detection limit was 0.5 mug. The present method was sensitive enough to determine sulforaphane in mature broccoli, broccoli sprouts, and commercial broccoli products. Sulforaphane concentration in broccoli sprout (1153 mg/100 g dry weight) was about 10 times higher than that of mature broccoli (44-171 mg/100 g dry weight). Therefore, the broccoli sprout is recommended as a source of sulforaphane-rich products. In contrast, we found that sulforaphane could not be detected in most of broccoli products, suggesting present commercial broccoli products having low quality.

Identification of a novel GLA mutation (F69 L) in a Japanese patient with late-onset Fabry disease.

Fabry disease is an X-linked recessive inborn error of glycosphingolipid catabolism caused by a mutation in the GLA gene. We sequenced the α-galactosidase A gene (GLA) of a patient who had been clinically diagnosed with late-onset Fabry disease. Abundant globotriaosylceramide was present in his urine, which indicated typical Fabry disease. Here, we report a novel hemizygous mutation, c.207C>A (Phe69 Leu), which caused a mild/late-onset form of Fabry disease.

Evaluation of Pax6 mutant rat as a model for autism.

Autism is a highly variable brain developmental disorder and has a strong genetic basis. Pax6 is a pivotal player in brain development and maintenance. It is expressed in embryonic and adult neural stem cells, in astrocytes in the entire central nervous system, and in neurons in the olfactory bulb, amygdala, thalamus, and cerebellum, functioning in highly context-dependent manners. We have recently reported that Pax6 heterozygous mutant (rSey(2)/+) rats with a spontaneous mutation in the Pax6 gene, show impaired prepulse inhibition (PPI). In the present study, we further examined behaviors of rSey(2)/+ rats and revealed that they exhibited abnormality in social interaction (more aggression and withdrawal) in addition to impairment in rearing activity and in fear-conditioned memory. Ultrasonic vocalization (USV) in rSey(2)+ rat pups was normal in male but abnormal in female. Moreover, treatment with clozapine successfully recovered the defects in sensorimotor gating function, but not in fear-conditioned memory. Taken together with our prior human genetic data and results in other literatures, rSey(2)/+ rats likely have some phenotypic components of autism.