BACKGROUND AND AIM: 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. METHODS AND 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.

Pharmacological treatment of a Sardinian patient affected by Autosomal Recessive Hypercholesterolemia (ARH)

MUNTONI, SANDRO;
2015

Abstract

BACKGROUND AND AIM: 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. METHODS AND 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.
Autosomal recessive hypercholesterolemia; Ezetimibe; NPC1L1 gene; PCSK9 gene; Rosuvastatin; Adaptor proteins, signal transducing; Anticholesteremic agents; Apolipoprotein A-I; Azetidines; Cholesterol, HDL; Cholesterol, LDL; Drug administration schedule; Female; Fluorobenzenes; Homozygote; Humans; Hydroxymethylglutaryl-CoA reductase inhibitors; Hypercholesterolemia; Membrane proteins; Middle aged; Polymorphism, single nucleotide; Proprotein convertases; Pyrimidines; Serine endopeptidases; Sulfonamides; Treatment outcome; Cardiology and cardiovascular medicine; Endocrinology, diabetes and metabolism; Internal medicine; Nutrition and dietetics
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/11584/133837
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