Aortic Xanthomatosis With Coronary Ostial Occlusion in a Child Homozygous for a Nonsense Mutation in ABCG8
A 5-year-old girl with a recent history of recurrent abdominal pain presented with acute respiratory distress that rapidly became asystolic. She then could not be revived. At autopsy, widespread yellow aortic xanthomas were seen, with severe atheromatous narrowing of both coronary ostia (Figure 1). The right and left anterior descending arteries showed focal marked atheromatous narrowing. Grossly and microscopically, there were no specific myocardial changes. Atheromas were also seen on the surfaces of the mitral valve leaflets and within the pulmonary artery. Aortic lesions extended to the level of the superior mesenteric artery, and atheromas were present in the branches of the aortic arch. Serum cholesterol concentration from a sample of post-mortem blood was 13.0 mmol/L (503 mg/dL). Parental lipoprotein profiles were relatively normal. Genomic DNA was isolated from frozen liver, and sequencing of the LDLR, APOB, ARH, and ABCG5 genes revealed no mutations. However, a novel C>G mutation was found at the second residue of codon nucleotide 107 in exon 3 of the ABCG8 gene, which predicted premature truncation of the protein product (S107X) (Figure 2). This mutation was absent from 400 normal chromosomes. The diagnosis of sitosterolemia, a rare autosomal recessive disorder of sterol absorption, was confirmed by documenting elevated serum total cholesterol and sitosterol concentrations in her sister, brother, and female cousin, aged 5, 4, and 8 years, respectively. Serum cholesterol was 10.8, 11.8, and 9.2 mmol/L (416, 455, and 356 mg/dL), respectively, and serum sitosterol concentrations were 282, 447, and 184 mg/L, respectively (reference range 0 to 10 mg/L) in these relatives, who were also shown to be homozygotes for S107X. The use of bile acid binding resins has greatly improved the lipoprotein profile in the 3 surviving homozygotes.
The editor of Images in Cardiovascular Medicine is Hugh A. McAllister, Jr, MD, Chief, Department of Pathology, St Luke’s Episcopal Hospital and Texas Heart Institute, and Clinical Professor of Pathology, University of Texas Medical School and Baylor College of Medicine.
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