Clinical and biochemical characterisation of patients with autosomal recessive hypercholesterolemia (ARH)

R. Fellin, G. Zuliani, M. Arca, P. Pintus, A. Pacifico, A. Montali, A. Corsini, M. Maioli

Research output: Contribution to journalArticlepeer-review


Background and Aim: Inherited hypercholesterolemias are common disorders characterised by elevated LDL-C levels and premature coronary heart disease. We have recently described a recessive form of hypercholesterolemia (autosomal recessive hypercholesterolemia, ARH) in which LDL catabolism is reduced because of a mutation in the gene coding for an adaptor protein that impairs LDL-receptor (LDL-R) activity in the liver. The aim of this study was to characterise in detail the phenotypes of subjects with homozygous and heterozygous ARH. Methods and Results: We have so far identified six Italian families with ARH and studied the clinical and biochemical characteristics of 11 homozygotes (age 13-47 years) and 12 obligate heterozygotes (age 42-83 years). The study protocol included an evaluation of the lipoprotein profile, LDL-R activity in fibroblasts, LDL binding activity, and apo E genotype; a structured questionnaire (CHD risk factors, medical history, current medications); a physical examination, resting and stress ECG, ultrasound examinations (heart, carotid arteries, Achilles tendons) and coronary angiography. The pedigrees were characterised by the absence of vertical transmission; consanguinity was documented in two families. Only the two previously described Sardinian mutations, ARH1 (c.432insA) and ARH2 (c.65G>A), were identified in the probands. All of the ARH homozygotes had large tendinous xanthomas, two had exertional angina, and four a positive stress ECG. None had experienced myocardial infarction or stroke. More than half had instrumental signs of atherosclerosis such as a positive stress ECG or positive carotid echo-doppler examination. The ARH heterozygotes were consistently normal and had a normal lipid profile. Conclusions: The ARH phenotype resembles that of familial hypercholesterolemia (FH) homozygotes, but ARH may be a less serious illness. The absence of vertical transmission, and the presence of mild coronary heart disease and consanguinity, can suggest a possible diagnosis of ARH. ARH might be considered a phenocopy of FH but heterozygous subjects seem to have a consistently normal phenotype.

Original languageEnglish
Pages (from-to)278-286
Number of pages9
JournalNutrition, Metabolism and Cardiovascular Diseases
Issue number5
Publication statusPublished - Oct 2003


  • Autosomal recessive
  • Hypercholesterolemia
  • Phenotype

ASJC Scopus subject areas

  • Food Science
  • Medicine (miscellaneous)
  • Cardiology and Cardiovascular Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics


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