Acute myocardial infarction in an 18 year old South Indian girl with familial hypercholesterolemia: a case report
© Kumar et al; licensee BioMed Central Ltd. 2008
Received: 07 June 2008
Accepted: 07 August 2008
Published: 07 August 2008
Familial hypercholesterolemia is a single gene disorder with an autosomal dominant pattern of inheritance. Here we report an 18 year old South Indian girl who presented with myocardial infarction. She had xanthomas and an elevated serum low density lipoprotein cholesterol (LDL-C). Her mother and maternal uncle had died at a young age due to myocardial infarction. Her only sibling, 15 year old younger sister also had xanthomas and an elevated LDL-C. This report is to emphasise the need to clinically recognize xanthomas and its association with elevated LDL-C, premature atherosclerosis and familial inheritance. Early diagnosis and early initiation of treatment will save the affected individual and the other family members.
Muller et el in the year 1938 reported a familial clustering of xanthoma, high cholesterol and myocardial infarction . In 1960, Khachadurian et al demonstrated that this clinical association termed familial hypercholesterolemia (FH) is a single gene disorder with an autosomal dominant pattern of inheritance . Further studies identified the association between improper metabolism of LDL and FH and that mutation in the LDL receptor gene (LDLR) located on chromosome 19 was responsible for this disorder [3–5]. FH is of 2 types, a homozygous type where both LDL receptor alleles are defective due to mutation and has a prevalence of 1 in 1 million persons world wide . In the heterozygous type only one LDL receptor allele is a mutant and is much more common with a prevalence of 1 in 500 persons worldwide . Here we report one such family from South India with features of premature atherosclerosis, high serum levels of LDL cholesterol and multiple xanthomas.
Fasting lipid profile values of the patient and her sister
Patient's sister's values
Patient's lipid levels after treatment
After 8 weeks therapy with maximal lipid lowering drugs
After 3 sessions of LDL apheresis
Our patient had myocardial infarction at a young age of 18 yrs with a lipid profile comprising a high LDL-C with normal triglycerides. She had xanthomas and corneal arcus. Her family history was classical with 2 generations being affected with premature atherosclerosis and both male and female individuals being affected equally. Hence this suggests an autosomal dominant disorder. Simon Broome's diagnostic criteria for familial hypercholesterolemia says a definite diagnosis of familial hypercholesterolemia can be made if either the total cholesterol concentration is above 7.5 mmol/liter in adults or the low density lipoprotein cholesterol concentration is above 4.9 mmol/liter in adults and if tendinous xanthomas were present in the patient or a first-degree relative [7, 8]. Our patient had total cholesterol of 16.8 mmol/l and a LDL-C of 14.6 mmol/l. She, her mother and her sister had xanthomas. Hence this confirms the diagnosis of familial hypercholesterolemia in our patient. She should have had the homozygous type of FH as the heterozygous type presents much later in adult life with coronary artery disease and LDL-C levels are generally less than 400 mg/dl .
Treatment options available for homozygous FH are lipid lowering drugs like statins, bile acid sequestrants, apheresis and liver transplantation . Lipid lowering drugs only result in modest reduction in LDL-C levels and apheresis is generally required when evidence of atherosclerosis is present. As liver is the most important tissue for removing circulating LDL, liver transplantation is an effective treatment option in this disorder. Our patient's LDL-C was refractory to drug therapy and hence she was initiated on LDL apheresis. Her response was satisfactory to this modality of treatment.
Clinical identification of xanthomas and knowledge of its association with coronary artery disease is essential for every physician as early diagnosis and treatment can prevent premature deaths due to MI. Also all the relatives in the family should be screened for dyslipidemia.
I have been having these swellings in my body for the last 7 years. I would have visited many doctors for various common ailments. Had they recognized this disorder in me much earlier I would not have had a heart attack. Atleast my sister will benefit as she has been diagnosed to have this disease and treatment will soon be initiated. After I get married I will also be careful with my children as I understand that they are also prone for this disease.
Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
Low Density Lipoprotein cholesterol
Low Density Lipoprotein Receptor gene
Tissue Plasminogen Activator
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