PHENOTYPIC CHARACTERIZATION OF A PATIENT HOMOZYGOUS FOR THE D558N LDLRECEPTOR GENE MUTATION

We describe the clinical, biochemical, and genetic features of a patie nt with true homozygous familial hypercholesterolemia due to the D558N low-density lipoprotein receptor gene mutation, previously designated FH Cincinnati-4. Functional flow-cytometric analysis of the LDL recep torR protein on upregulated EBV-transformed lymphocytes indicated redu ction of the number of receptors on the cell surface by 87% and reduct ion of receptor activity by 89% compared to control cells. With drugs and a portacaval shunt operation, performed when the patient was 15 ye ars old, serum cholesterol was reduced from about 28 to about 15 mmol/ l. He died at the age of 32 of a myocardial infarction. The autopsy sh owed generalized atherosclerosis, especially in the coronary arteries, which were severely stenosed proximally. A rare finding was a large i ntracranial xanthoma that apparently had been asymptomatic.