Complete Apo AI deficiency in an Iraqi Mandaean family: case studies and review of the literature.
Complete apo A1 deficiency is a rare genetic disorder that has been associated with premature atherosclerosis. We describe a family of Iraqi Mandaean background with complete apo A1 deficiency caused by a new nonsense mutation in the APOA1 gene. Interestingly, there were marked differences in the clinical presentation of the two homozygotes in this family. A 35-year-old woman presented with xanthelasmas and xanthomas but showed only minimal changes on cardiovascular examinations and no clinical symptoms. However, her 37-year-old brother was diagnosed with myocardial infarction at age 35. In addition, both the homozygotes had elevated C-reactive protein levels. The C-reactive protein levels increased three-fold during pregnancy, then decreased postpartum and further decreased with statin treatment. Cholesterol ester transfer protein mass was close to the upper reference range, whereas the activity was low, likely because of the lack of the substrate. Here, we characterize the phenotype and genotype of the first Middle Eastern family with apo A1 deficiency and compare and contrast the findings in the two homozygous siblings and review the previously reported cases of apo A1 deficiency.
Healthy Heart Program Prevention Clinic, St. Paul's Hospital, 1081 Burrard Street, Vancouver, British Columbia, Canada.
Ahmad
A
Al-Sarraf
Khalid
K
Al-Ghofaili
David R
DR
Sullivan
Kishor M
KM
Wasan
Robert
R
Hegele
Jiri
J
Frohlich
D000328:Adult; D016632:Apolipoprotein A-I / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D002097:C-Reactive Protein / Q000032:analysis; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D018389:Codon, Nonsense; D005260:Female; D005464:Fluorobenzenes / Q000627:therapeutic use; D005838:Genotype; D006720:Homozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use; D006949:Hyperlipidemias / Q000175:diagnosis / Q000188:drug therapy / Q000208:ethnology; D007493:Iraq / Q000208:ethnology; D008077:Lipoproteins, LDL / Q000097:blood; D008297:Male; D010375:Pedigree; D010641:Phenotype; D011247:Pregnancy; D011743:Pyrimidines / Q000627:therapeutic use; D000068718:Rosuvastatin Calcium; D017422:Sequence Analysis, DNA; D013449:Sulfonamides / Q000627:therapeutic use
D016632:Apolipoprotein A-I; D053480:Cholesterol Ester Transfer Proteins; D018389:Codon, Nonsense; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008077:Lipoproteins, LDL; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium; D002097:C-Reactive Protein