title: Pharmacological treatment of a Sardinian patient affected by Autosomal Recessive Hypercholesterolemia (ARH).
abstract: OBJECTIVE
  Previous studies have shown that patients with autosomal recessive hypercholesterolemia (ARH) resulting from mutations in LDLRAP1 gene have a less severe cardiovascular involvement than familial hypercholesterolemia homozygotes, lower levels of low-density lipoprotein cholesterol (LDL-C), and higher levels of high-density lipoprotein cholesterol (HDL-C). In addition, ARH patients seem to be more responsive to the lipid-lowering drugs. The aim was to test the effect of a combined drug treatment in an ARH patient in the absence of plasmapheresis.
  
  
  RESULTS
  Here we report the lipid-lowering effect of rosuvastatin (60 mg/day) associated with ezetimibe (10 mg/day) in a single ARH patient. The sequencing of LDLRAP1 gene showed that the patient was homozygous for the c.432insA mutation. During a 6-month treatment, we observed an 80% reduction of LDL-C and a significant increase of HDL-C and ApoA-I. Some sequence variations in PCSK9 and NPC1L1 genes found in this patient may have contributed to the success of drug treatment.
  
  
  CONCLUSIONS
  Our findings, although limited to a single case, suggest that in many ARH patients the LDL-C goal may be reached with the more potent statins associated with ezetimibe in the absence of extracorporeal procedures.
authors: Oncology and Molecular Pathology Unit, Department of Biomedical Sciences, University of Cagliari, Italy; Centre for Metabolic Diseases and Atherosclerosis, The ME.DI.CO. Association, Cagliari, Italy. Electronic address: smuntoni@unica.it.
authors: Sandro
authors: S
authors: Muntoni
authors: Department of Internal Medicine, University of Genova, Italy.
authors: Livia
authors: L
authors: Pisciotta
authors: Centre for Metabolic Diseases and Atherosclerosis, The ME.DI.CO. Association, Cagliari, Italy.
authors: Sergio
authors: S
authors: Muntoni
authors: Department of Internal Medicine, University of Genova, Italy.
authors: Stefano
authors: S
authors: Bertolini
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D016632:Apolipoprotein A-I / Q000097:blood; D001384:Azetidines / Q000627:therapeutic use*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004334:Drug Administration Schedule; D000069438:Ezetimibe; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use*; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000188:drug therapy* / Q000235:genetics; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D000068718:Rosuvastatin Calcium; D012697:Serine Endopeptidases / Q000235:genetics; D013449:Sulfonamides / Q000627:therapeutic use*; D016896:Treatment Outcome; D006952:Hyperlipoproteinemia Type III
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000924:Anticholesteremic Agents; D016632:Apolipoprotein A-I; D001384:Azetidines; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; C469745:LDLRAP1 protein, human; D008565:Membrane Proteins; D026901:Membrane Transport Proteins; C410800:NPC1L1 protein, human; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; C472125:PCSK9 protein, human; D000071449:Proprotein Convertase 9; D043484:Proprotein Convertases; D012697:Serine Endopeptidases; D000069438:Ezetimibe
keywords: Autosomal recessive hypercholesterolemia; Ezetimibe; NPC1L1 gene; PCSK9 gene; Rosuvastatin