1996 年度実績報告書

脂肪酸β酸化異常症の早期診断と病因検索体制の確立

研究課題

研究課題/領域番号	08307008
応募区分	総合
研究機関	島根医科大学
研究代表者	山口清次島根医科大学, 医学部, 教授 (60144044)
研究分担者	鈴木康之岐阜大学, 医学部, 講師 (00163014) 澤田淳京都府立医科大学, 医学部, 教授 (10079874) 橋本隆信州大学, 医学部, 教授 (80009935)
キーワード	脂肪酸β酸化異常症 / ペルオキシソーム病 / スクリーニング / 質量分析 / 酵素診断 / 遺伝子解析 / アシルカルニチン
研究概要	わが国における脂肪酸β酸化異常症の病因検索体制を確立するために、今年度は、質量分析法による生化学診断法、酵素診断、遺伝子診断法の確立に向けた研究を中心に行った. (a)山口は、有機酸分析のGC/MSデータ自動処理・診断システムを確立した.ペルオキシソーム病の尿中有機酸分析によるスクリーニング法を検討し、新しい診断マーカーであるジカルボキシルエポキシドの診断的意義を明らかにした.またわが国における脂肪酸β酸化異常症患者の実態調査(アンケート、現在集計中)を行った. (b)橋本は脂肪酸β酸化に関与する酵素の解析法を中心に検討した.橋本らは数年前ミトコンドリア脂肪酸β酸化系の新しい酵素(極長鎖アシル-CoA脱水素酵素、三頭酵素)を発見し、その欠損症はこれまで外国の症例が中心に同定されてきたが、今年度わが国の症例についても分子レベルで検索を進めた.さらに今年度ペルオキシソーム系の新しい酵素(D型二頭酵素)を発見し、その欠損症の存在を確認した. (c)沢田はタンデムマスを用いて、血中アシルカルニチン分析による診断法を検討してきた.今年度、患者は見い出されなかったが、脂肪酸β酸化異常症に多い乳幼児突然死症候群38症例について脂肪酸代謝異常スクリーニングを行った.また脂肪酸代謝に役割を果たすカルニチンの動態を調べることを目的としてカルニチン前駆体の測定法を確立した. (d)鈴木は、ペルオキシソーム病の分子レベルでの診断法を中心に検討し、今年度4例のペルオキシソーム病の検索を行った.アシル-CoAオキシダーゼ欠損症2例は遺伝子レベルでホモの変異を同定し、他の2例は橋本らの新しく発見したD型二頭酵素の欠損であった. 来年度は、わが国における脂肪酸代謝異常症のスクリーニング、酵素検索による確定診断の体制作りに重点をおいて研究を進めたい.

研究成果
(33件)

すべてその他

すべて文献書誌 (33件)

[文献書誌] Souri M: "Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency:Identification and characterization of mutant VLCAD cDNAs from four patients." Am J Hum Genet. 58. 97-106 (1996)
[文献書誌] Orii KE: "Formation of the enzyme complex in mitochondria is required for function of trifunctional b-oxidation protein." Biochem Biophys Res Comm.219. 773-777 (1996)
[文献書誌] Imai J: "Dtermination of the 8-methyl ether of xanthurenic acid in human serum by high-performance liquid chromatography with fluorescence detection." J Chromatography. 679. 204-207 (1996)
[文献書誌] Shigematsu Y: "Prenatal diagnosis of organic acidemias based on amniotic fluid levels of acylcarnitnies." Pediatr Res. 39. 680-684 (1996)
[文献書誌] Itoh T: "Effect of carnitine administration on glycine metabolism in patients with isovaleric acidemia:significance of acetylcarnitine determination to estimate the proper carnitine dose." Tohoku J Exp Med. 179. 101-109 (1996)
[文献書誌] Fukao T: "Immunotitration analysis of cytosolic acetoacetyl-coenzyme A thiolase activity in human fibroblasts." Pediatr Res. 39. 1055-1058 (1996)
[文献書誌] Masuno M: "Assignment of the human cytosolic acetoacetyl-coenzyme A thiolase (ACAT2) gene to chromosome 6q25.3-q26." Genomics. 36. 217-218 (1996)
[文献書誌] Yasushi Uchida: "Purification and properties of rat liver peroxisomal very-long-chain acyl-CoA synthetase." J Biochem. 119. 565-571 (1996)
[文献書誌] Akio Kobayashi: "Two mitochondrial 3-hydroxyacyl-CoA dehydrogenase in bovine liver." J Biochem. 119. 775-782 (1996)
[文献書誌] Seiichi Ushikubo: "Molecular characterization of mitochondrial trifunctional protein deficiency:Formation of the enzyme complex is important for stabilization of both α-and β-subunits." Am J Hum Genet. 58. 979-988 (1996)
[文献書誌] Mari Kono: "Two distinct long-chain-acyl-CoA synthetases in guinea pig Harderian gland." Eur J Biochem. 238. 104-111 (1996)
[文献書誌] Takashi Hashimoto: "A new inhibitor of mitochondrial fatty acid oxidation" J Biochem. 119. 1196-1201 (1996)
[文献書誌] Ling Ling Jiang: "Purification and properities of human D-3-hydroxyacyl-CoA dehydratase:Medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase." J Biochem. 120. 624-632 (1996)
[文献書誌] Ling Ling Jiang: "Purification and properties of rat D-3-hydroxyacyl-CoA dehydratase:D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein." J Biochem. 120. 633-641 (1996)
[文献書誌] Toshifumi Aoyama: "Assignment of the human mitochondrial very-long-chain acyl-CoA dehydrogenase gene (LCAD) to 17p13 by in situ hydridization." Genomics. 37. 144-145 (1996)
[文献書誌] Shimozawa N: "Correction by gene.expression of biochemical abnormalities in fibroblasts from Zelweger patients." Pediatr Res. 39. 812-815 (1996)
[文献書誌] Suzuki Y: "Trial of docosahexaenoic acid supplementation on a Japanese patient with a peroxisome biogenesis defect." Acta Paediatr Jpn. 38. 520-523 (1996)
[文献書誌] Fukuda S: "Human peroxisome assembly factor-2 (PAF-2):a gene responsible for group C peroxisome biogenesis disorder in humans." Am J Hum Genet. 59. 1210-1220 (1996)
[文献書誌] Ling Ling Jiang: "Purification and properities of human D-3-hydroxyacyl-CoA dehydratase:Medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase." J Biochem. 120. 624-632 (1996)
[文献書誌] Ling Ling Jiang: "Purification and properties of rat D-3-hydroxyacyl-CoA dehydratase:D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein." J Biochem. 120. 633-641 (1996)
[文献書誌] Toshifumi Aoyama: "Assignment of the human mitochondrial very-long-chain acyl-CoA dehydrogenase gene (LCAD) to 17p13 by in situ hydridization" Genomics. 37. 144-145 (1996)
[文献書誌] Shimozawa N: "Correction by gene expression of biochemical abnormalities in fibroblasts from Zelweger patients." Pediatr Res. 39. 812-815 (1996)
[文献書誌] Suzuki Y: "Trial of docosahexaenoic acid supplementation on a Japanese patient with a peroxisome biogenesis defect." Acta Paediatr Jpn. 38. 520-523 (1996)
[文献書誌] Fukuda S: "Human peroxisome assembly factor-2 (PAF-2):a gene responsible for group C peroxisome biogenesis disorder in humans." Am J Hum Genet. 59. 1210-1220 (1996)
[文献書誌] Akaboshi S: "Peroxisomal bifunctional enzyme deficiency:serial neurophysiological examinations of a case." Brain Dev. (in press).
[文献書誌] Shimozawa N: "A novel mutation, R125X in peroxisome assembly factor-1 responsible for Zellweger syndrome." Human Mutat. (in press).
[文献書誌] Suzuki Y: "Use of buccal smears for rapid detection of peroxisomes." Eur J Pediatr. (in press).
[文献書誌] Inoue K: "Carrier identification of X-linked adrenoleukodystrophy by measurement of very long chain fatty acids and lignoceric acid oxidation." Clin Genet. (in press).
[文献書誌] Imamura A: "Two novel missense mutations in ATP-binding domain of adrenoleukodystrophy gene:immunoblotting and immunocytological study of two patients." Clin Genet. (in press).
[文献書誌] 寺田直人: 医学のあゆみ. 177(6). 471-472 (1996)
[文献書誌] 山口清次(井村裕夫編): "最新内科学体系第8巻 -II型グルタル酸血症-" 中山書店、東京, 354-356 (1996)
[文献書誌] 山口清次(井村裕夫編): "最新内科学体系第8巻 -β-ケトチオラーゼ欠損症-" 中山書店、東京, 138-142 (1996)
[文献書誌] 山口清次: "小児疾患診療のための病態生理(小児内科Vol.28増刊号)-グルタル酸血症-" 東京医学社, 281-283 (1996)

1996 年度 実績報告書

脂肪酸β酸化異常症の早期診断と病因検索体制の確立

研究代表者

山口 清次 島根医科大学, 医学部, 教授 (60144044)

研究成果

[文献書誌] Souri M: "Mutation analysis of very-long-chain acyl-coenzyme A dehydrogenase (VLCAD) deficiency:Identification and characterization of mutant VLCAD cDNAs from four patients." Am J Hum Genet. 58. 97-106 (1996)

[文献書誌] Orii KE: "Formation of the enzyme complex in mitochondria is required for function of trifunctional b-oxidation protein." Biochem Biophys Res Comm.219. 773-777 (1996)

[文献書誌] Imai J: "Dtermination of the 8-methyl ether of xanthurenic acid in human serum by high-performance liquid chromatography with fluorescence detection." J Chromatography. 679. 204-207 (1996)

[文献書誌] Shigematsu Y: "Prenatal diagnosis of organic acidemias based on amniotic fluid levels of acylcarnitnies." Pediatr Res. 39. 680-684 (1996)

[文献書誌] Itoh T: "Effect of carnitine administration on glycine metabolism in patients with isovaleric acidemia:significance of acetylcarnitine determination to estimate the proper carnitine dose." Tohoku J Exp Med. 179. 101-109 (1996)

[文献書誌] Fukao T: "Immunotitration analysis of cytosolic acetoacetyl-coenzyme A thiolase activity in human fibroblasts." Pediatr Res. 39. 1055-1058 (1996)

[文献書誌] Masuno M: "Assignment of the human cytosolic acetoacetyl-coenzyme A thiolase (ACAT2) gene to chromosome 6q25.3-q26." Genomics. 36. 217-218 (1996)

[文献書誌] Yasushi Uchida: "Purification and properties of rat liver peroxisomal very-long-chain acyl-CoA synthetase." J Biochem. 119. 565-571 (1996)

[文献書誌] Akio Kobayashi: "Two mitochondrial 3-hydroxyacyl-CoA dehydrogenase in bovine liver." J Biochem. 119. 775-782 (1996)

[文献書誌] Seiichi Ushikubo: "Molecular characterization of mitochondrial trifunctional protein deficiency:Formation of the enzyme complex is important for stabilization of both α-and β-subunits." Am J Hum Genet. 58. 979-988 (1996)

[文献書誌] Mari Kono: "Two distinct long-chain-acyl-CoA synthetases in guinea pig Harderian gland." Eur J Biochem. 238. 104-111 (1996)

[文献書誌] Takashi Hashimoto: "A new inhibitor of mitochondrial fatty acid oxidation" J Biochem. 119. 1196-1201 (1996)

[文献書誌] Ling Ling Jiang: "Purification and properities of human D-3-hydroxyacyl-CoA dehydratase:Medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase." J Biochem. 120. 624-632 (1996)

[文献書誌] Ling Ling Jiang: "Purification and properties of rat D-3-hydroxyacyl-CoA dehydratase:D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein." J Biochem. 120. 633-641 (1996)

[文献書誌] Toshifumi Aoyama: "Assignment of the human mitochondrial very-long-chain acyl-CoA dehydrogenase gene (LCAD) to 17p13 by in situ hydridization." Genomics. 37. 144-145 (1996)

[文献書誌] Shimozawa N: "Correction by gene.expression of biochemical abnormalities in fibroblasts from Zelweger patients." Pediatr Res. 39. 812-815 (1996)

[文献書誌] Suzuki Y: "Trial of docosahexaenoic acid supplementation on a Japanese patient with a peroxisome biogenesis defect." Acta Paediatr Jpn. 38. 520-523 (1996)

[文献書誌] Fukuda S: "Human peroxisome assembly factor-2 (PAF-2):a gene responsible for group C peroxisome biogenesis disorder in humans." Am J Hum Genet. 59. 1210-1220 (1996)

[文献書誌] Ling Ling Jiang: "Purification and properities of human D-3-hydroxyacyl-CoA dehydratase:Medium-chain enoyl-CoA hydratase is D-3-hydroxyacyl-CoA dehydratase." J Biochem. 120. 624-632 (1996)

[文献書誌] Ling Ling Jiang: "Purification and properties of rat D-3-hydroxyacyl-CoA dehydratase:D-3-hydroxyacyl-CoA dehydratase/D-3-hydroxyacyl-CoA dehydrogenase bifunctional protein." J Biochem. 120. 633-641 (1996)

[文献書誌] Toshifumi Aoyama: "Assignment of the human mitochondrial very-long-chain acyl-CoA dehydrogenase gene (LCAD) to 17p13 by in situ hydridization" Genomics. 37. 144-145 (1996)

[文献書誌] Shimozawa N: "Correction by gene expression of biochemical abnormalities in fibroblasts from Zelweger patients." Pediatr Res. 39. 812-815 (1996)

[文献書誌] Suzuki Y: "Trial of docosahexaenoic acid supplementation on a Japanese patient with a peroxisome biogenesis defect." Acta Paediatr Jpn. 38. 520-523 (1996)

[文献書誌] Fukuda S: "Human peroxisome assembly factor-2 (PAF-2):a gene responsible for group C peroxisome biogenesis disorder in humans." Am J Hum Genet. 59. 1210-1220 (1996)

[文献書誌] Akaboshi S: "Peroxisomal bifunctional enzyme deficiency:serial neurophysiological examinations of a case." Brain Dev. (in press).

[文献書誌] Shimozawa N: "A novel mutation, R125X in peroxisome assembly factor-1 responsible for Zellweger syndrome." Human Mutat. (in press).

[文献書誌] Suzuki Y: "Use of buccal smears for rapid detection of peroxisomes." Eur J Pediatr. (in press).

[文献書誌] Inoue K: "Carrier identification of X-linked adrenoleukodystrophy by measurement of very long chain fatty acids and lignoceric acid oxidation." Clin Genet. (in press).

[文献書誌] Imamura A: "Two novel missense mutations in ATP-binding domain of adrenoleukodystrophy gene:immunoblotting and immunocytological study of two patients." Clin Genet. (in press).

[文献書誌] 寺田直人: 医学のあゆみ. 177(6). 471-472 (1996)

[文献書誌] 山口清次(井村裕夫編): "最新内科学体系第8巻 -II型グルタル酸血症-" 中山書店、東京, 354-356 (1996)

[文献書誌] 山口清次(井村裕夫編): "最新内科学体系第8巻 -β-ケトチオラーゼ欠損症-" 中山書店、東京, 138-142 (1996)

[文献書誌] 山口清次: "小児疾患診療のための病態生理(小児内科Vol.28増刊号)-グルタル酸血症-" 東京医学社, 281-283 (1996)

1996 年度実績報告書

山口清次島根医科大学, 医学部, 教授 (60144044)