A Young Girl with Vasospastic Angina Associated with Mutation in Endothelial Nitric Oxide Synthase Gene

Abstract

A 13-year-old girl was successfully recuperated from cardiopulmonary arrest shortly after running 80 m in a competition. The electrocardiogram, echocardiogram and ¹²³ I-MIBG myocar dial scintigraphic imaging indicated myocardial ischemia in the anteroseptal wall of the left ventricle. Coronary angiography during the recovery phase revealed no stenotic lesions, and spasms of the left anterior descending artery and the left circumflex artery could be provoked by acetylcholine. The endothelial nitric oxide synthase gene abnormality associated with coronary spasms was examined. The patient had the T^-786→C, A^-922→G, and T-¹⁴⁶⁸ →A mutations in the 5'-flanking region on one allele of the endothelial nitric oxide synthase gene. To the authors' knowledge, she represents the first case of life-threatening coronary spasms in childhood associated with mutations in the endothelial nitric oxide synthase gene.

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References

Nakamura M. , Takeshita A. , Nose Y. : Clinical characteristics associated with myocardial infarction, arrhythmia, and sudden death in patients with vasospastic angina. Circulation 75:1110-1116, 1987.

MacAlin RN: Cardiac arrest and sudden unexpected death in variant angina: Complications of coronary spasm that can occur in the absence of severe organic coronary stenosis. Am Heart J 125:1011-1017, 1993.

Wilkers D. , Donner R. , Black I. , et al: Variant angina in an 11 year old boy. J Am Coll Cardiol 5:761-764, 1985.

Ivay D. , Kaye J. , Flitter D. , et al: Variant angina in an adolescent. Pediatr Cardiol 15:45-47, 1994.

Hosoi T. , Koyama Y. , Tange S. , et al: Acute myocardial infarction due to coronary vasospasm in a 13-year-old boy. Jpn Circ J 61:536-542, 1997.

Yoshimura M. , Yasue H. , Nakayama M. , et al: A missense Glu298Asp variant in the endothelial nitric oxide synthase gene is associated with coronary spasm in the Japanese. Hum Genet 103:65-69, 1998.

Shimasaki Y. , Yasue H. , Yoshimura M. , et al: Association of the missense Glu298Asp variant of the endothelial nitric oxide synthase gene with myocardial infarction . J Am Coll Cardiol 31:1506-1510, 1998 .

Nakayama M. , Yasue H. , Yoshimura M. , et al: T-786→C Mutation in the 5'-flanking region of the endothelial nitric oxide synthase gene is associated with coronary spasm. Circulation 99:2864-2870, 1999.

Liao YL , Saku K. , Ou J. , et al: A missense mutation of the nitric oxide synthase (eNOS) gene (Glu298Asp) in five patients with coronary artery disease. Angiology 50:671-676, 1999.

10.

Yoshimura M. , Yasue H. , Nakayama M. , et al: Genetic risk factors for coronary artery spasm: Significance of endothelial nitric oxide synthase gene T-786→C and missense Glu298Asp variants. J Invest Med 48:367-374, 2000.

11.

Discoll DJ , Edwards WD : Sudden unexpected death in children and adolescents. J Am Cardiol 5 :118B-121B, 1985.

12.

Nimura I. , Maki T. : Sudden cardiac death in childhood. Jpn Circ J 53:1571-1580, 1989.

13.

Ohkuni M. : Sudden death in school children in Japan. J Jpn Med Assoc 113:685-688, 1995.

14.

Richard RL : Sudden death from cardiac causes in children and young adults. N Engl J Med 334:1039-1044, 1996 .

15.

Takada K. , Nagashima M. , Takada H. , et al: Sudden death in school children: Role of physical activities and meteorological conditions. Pediatr Int 41:151-156, 1999.

16.

Yasue H. , Matsuyama K. , Matsuyama K. , et al: Responses of angiographically normal human coronary arteries to intracoronary injection of acetylcholine by age and segment. Circulation 81:482-490, 1990.