Familial hypercholesterolemia

To the Editor,

This is in reference to the recently published letter on homozygous familial hypercholesterolemia.[1]

Last year we came across a case of homozygous hypercholesterolemia with cutaneous and tendinous xanthoma in a seven year old male child.[2] At the time of reporting we could not examine other members of his family. Later on we managed to take a detailed family history and had the chance of examining some other members of his family.

The case we reported was a seven-year-old male child, born of a consanguineous marriage (where his father married one of his maternal sister), presented with multiple asymptomatic, yellowish, papular and papulo-nodular lesions over his knees, elbows and buttocks. Tuberous lesions on buttocks, tendinous lesions on extensor tendons of hands and xanthelasma palpebrarum on inner canthus of eyes were also present.

The child was of normal built with mild mental retardation. He was found to be euglycemic with moderate eosinophilia (736/cmm), serum triglyceride level was 70%mg, cholesterol 730mg% with LDL-C 688mg%,HDL-C 28mg% and VLDL-C 14mg% respectively.

We went on compiling data on other members of his family. It was found that, his grandmother had papular lesion on inner canthus of both her eyes. She had hypertension and died of acute myocardial infarction at the age of forty-two. She was married to her cousin brother. This marriage produced six offsprings (3 male, 3 female).The third one was a male who suddenly died three years back due to a possible (VA at the age of 26 years. He also had some skin xanthoma-like lesions.

The fifth one, also a male, has got tendinous and tuberous xanthoma with cholesterol level 355mg%, LDL 322 mg%, VLDL 16mg% and HDL 25mg% at the age of twenty eight. His parents are without any symptoms.

Primary hypercholesterolemia usually occurs as a monogenic defect in lipoprotein catabolism by a mutation in the gene for the LDL receptor. The rate at which the LDL is removed from the plasma is determined by the heterozygous or the homozygous state of the individual.[3],[4] In heterozygous state it is removed at two third of normal rate resulting in two to three fold elevation in plasma LDL (Case C). But in homozygous state, LDL is removed at only one third of normal rate and that results in six to eight fold elevation of plasma LDL[3],[4] (Case D). Heterozygous hypercholesterolemia is not that uncommon (1 in 500 persons), clinically manifesting between third and sixth decades. But only one in one million persons in general population inherit two copies of familial hypercholesterolemia gene and is a homozygote for the disorder.[4]

This family has one distinct homozygous (Case D), one heterozygous (Case C) and other two(Cases A and B) of possible heterozygous hypercholesterolemia.

Even though this is rare but marriage between cousin brothers and sisters, over two successive generations invited this disastrous consequence in this family.