A 25-year-old with severe coronary artery disease

• Published in: The Lancet (British edition) Vol. 357; no. 9250; p. 116
• Main Authors: Ward, Michael R, Herity, Niall A, Lee, David P, Yeung, Alan C
• Format: Journal Article
• Language: English
• Published: London Elsevier Ltd 13.01.2001; Lancet; Elsevier Limited
• Subjects: Adult; Biological and medical sciences; Cardiology. Vascular system; Cardiovascular disease; Coronary Disease - diagnosis; Coronary heart disease; Female; Heart; Heterogeneity; Homozygosity; Humans; Medical sciences; Mutation; Severity of Illness Index; Young adults; Human; Nervous system diseases; Cardiovascular disease; Metabolic diseases; Coronary heart disease; Enzymopathy; Cerebral disorder; Genetic disease; Case study; Gaucher disease; Etiology; Central nervous system disease; Adult; Female; Lipoidosis
• ISSN: 0140-6736; 1474-547X
• DOI: 10.1016/S0140-6736(00)03546-7

The heterogeneity and variable severity of clinical features in Gaucher's disease are puzzling, considering that all patients have dysfunctional mutations inbetaglucocerebrosidase. Recently, genotype/phenotype correlations have begun to emerge: Type 1 (non-neuronopathic) Gaucher's is frequently due to homozygosity for the N370S mutation while ILA44P/IA44P often underlies Type II (acute neuronopathic) Gaucher's. The wide variation in type III (subacute neuronopathic) disease is, not surprisingly, due to multiple gene defects. However, a specific and very consistent phenotype has recently been identified for patients homozygous for the D409H(1342C) mutation characterised by oculomotor apraxia and thickening and calcification of the mitral and aortic valves and ascending aorta.' Although involvement of the coronary arteries has not previously been reported with this genotype, coronary artery stenoses with eccentric intimal fibrosis were noted at necropsy in a boy with type Ill Gaucher's disease of unknown genotype but with aortic fibrosis and calcification.' Many D409H patients have undergone valve replacement but may not have had preoperative coronary angiography due to their youth. The high rate of sudden death in this syndrome, previously attributed to valve disease, may also be due to unrecognised coronary stenoses. The underlying cause for severe coronary disease with recurrent restenosis is uncertain but may relate to macrophage activation and proliferative cytokine (TNF-a and IL-1beta) production3 which have been linked to atherosclerosis and restenosis. In addition, increased concentrations of the atherosclerosis-associated enzyme chitinase in Gaucher's disease may enhance vascular levels of hyaluronan, a glycoprotein implicated in smooth muscle cell (SMC) migration and restenosis.'