Molecular genetic analysis of pyridoxine-nonresponsive homocystinuric siblings with different blood methionine levels during the neonatal period

Two mutations in the cystathionine β-synthase (CBS) gene were found in two Japanese siblings with pyridoxine non-responsive homocystinuria who had different methionine levels in their blood during the neonatal period. Both patients were com-pound heterozygotes of two mutant alleles:one had an A-to-G transition at nucleotide194 (A194G) that caused a histidine-to-arginine substitution at position 65 of the protein (H65R), while the other had a G-to-A transition at nucleotide346 (G346A) which resulted in a glycine-to-arginine substitution at position 116 of the protein (G116R). The two mutant proteins were separately expressed in Escherichia coli, and they completely lacked catalytic activity. Despite their identical genotypes and almost equal protein intake, these siblings showed different levels of blood methionine during the neonatal period, suggesting that the level of methionine in blood is determined not only by the defect in the CBS gene and protein intake, but also by the activity of other enzymes involved in methionine and homocysteine metabolism, especially during the neonatal period. Therefore, high-risk newborns who have siblings with homocystinuria, even if the level of methionine in their blood is normal in a neonatal mass screening, should be followed up and diagnosed by an assay of enzyme activity or a gene analysis so that treatment can be begun as soon as possible to prevent the development of clinical symptoms. In addition, a new, more sensi-tive method for the mass screening of CBS deficiency in neonates should be developed

Two siblings with vitamin B6-nonresponsive cystathionine β-synthase deficiency and differing blood methionine levels during the neonatal period

We present two siblings with vitamin B6-nonresponsive homocystinuria due to a deficiency of cystathionine β-synthase who had different levels of methionine in the blood during the neonatal period, even though they had the same genetic defect. One of them was missed in the screening of newborns for homocystinuria. Special care should be taken in screening neonates for homocystinuria using the blood level of methionine

ピルビンサン ダッスイソ コウソ フクゴウタイ イジョウショウ ジョジ カンジャ ノ イデンシ シンダン システム ノ カクリツ

Pyruvate dehydrogenase (PDH) complex deficiency is one of the important causes of congenital lactic acidemia and mostly due to defect in the α subunit of PDH (E1α), of which gene is located on the X chromosome. The diagnosis of the PDH E1α deficiency is usually established by the measurement of the PDH complex activity in cultured cells. However, some female patients, who are heterozygous for the mutant allele, cannot be diagnosed only by the assay of PDH complex activity, because of the skewed X-chromosome inactivation in cultured cells. Then, we established DNA diagnostic system for PDH E1α deficiency using X inactivation assay, no RI PCR-SSCP, and direct sequencing. With this DNA diagnostic system we could diagnose 4 female patients as PDH E1α deficiency from 14 female patients who were suspected PDH complex deficiency from the clinical features and concentrations of lactate and pyruvate in the blood but showed normal PDH complex activity in their cultured cells. These results indicate that this DNA diagnostic system for PDH E1 αdeficiency is very useful

大腸3D-CT検査(CT-colonography)における腸管外病変の検出

大腸疾患患者を対象に大腸3D-CT検査(CT-colonography)を施行し,腸管外病変の検出率,検出された腸管外病変の臨床的重要性の分類および大腸疾患の有無と腸管外病変の関係の3項目について検討した.その結果,対象者112例のうち84.8%の症例に少なくとも1つ以上の腸管外病変を認めた.また,対象例のうち33例(29.5%)にカテゴリーE4(臨床上重要な所見を有する)群に分類される腸管外病変を認めた.そして,カテゴリーE4群のうち大腸内視鏡検査で24例(72.7%)が大腸癌と,4例(12.1%,全例に対する比率:3.6%)が所見なしと診断された.これらのことから,大腸疾患およびその疑いを有する症例にCT-colonographyを施行することは,大腸疾患を有する症例はもとより内視鏡検査で所見なしと診断された症例においても,重大な腸管外病変の早期発見に有用である

Reference values for the locomotive syndrome risk test quantifying mobility of 8681 adults aged 20–89 years: A cross-sectional nationwide study in Japan

Background The locomotive syndrome risk test was developed to quantify the decrease in mobility among adults, which could eventually lead to disability. The purpose of this study was to establish reference values for the locomotive syndrome risk test for adults and investigate the influence of age and sex. Methods We analyzed 8681 independent community dwellers (3607 men, 5074 women). Data pertaining to locomotive syndrome risk test (the two-step test, the stand-up test, and the 25-question geriatric locomotive function scale [GLFS-25]) scores were collected from seven administrative areas of Japan. Results The reference values of the three test scores were generated and all three test scores gradually decreased among young-to-middle-aged individuals and rapidly decreased in individuals aged over 60 years. The stand-up test score began decreasing significantly from the age of 30 years. The trajectories of decrease in the two-step test score with age was slightly different between men and women especially among the middle-aged individuals. The two physical test scores were more sensitive to aging than the self-reported test score. Conclusion The reference values generated in this study could be employed to determine whether an individual has mobility comparable to independent community dwellers of the same age and sex