Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children.
The clinical observation and treatment of young children with sitosterolemia has rarely been reported. We report clinical, biochemical, and molecular genetic observations and treatment outcomes for five Chinese children from four separate families presenting with sitosterolemia in whom we identified two new (Y329X, G269R) and three known (R446X, N437K, R389H) mutations in the ABCG5 gene. The R389H mutation was found in 50% of alleles. Three of these five patients received cholestyramine therapy with a very good response. However, all patients discontinued this therapy because of poor compliance. Finally, all patients were on ezetimibe therapy and had satisfactory total serum cholesterol levels, though their plant sterol levels were still higher than normal. Another noteworthy finding is that a female infant had a serum cholesterol level of 654 mg/dl at 7 months of age, despite being breast fed (with very tiny amounts of plant sterols) since birth and undergoing 4 months of ezetimibe administration. Although she failed to respond to ezetimibe during this period, she did show improvement when the therapy was started again at 2 years of age. It is possible that another 23-month-old female patient also responded more slowly to ezetimibe treatment than older patients.
Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, No. 155, Sec. 2, Linong Street, Taipei, 112, Taiwan, Republic of China. dmniu1111@yahoo.com.tw
Dau-Ming
DM
Niu
Kah-Wai
KW
Chong
Ju-Hui
JH
Hsu
Tina Jui-Ting
TJ
Wu
Hsiao-Chi
HC
Yu
Cheng-Hung
CH
Huang
Ming-Yu
MY
Lo
Ching Fai
CF
Kwok
Lisa E
LE
Kratz
Low-Tone
LT
Ho
D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters / Q000235:genetics*; D000924:Anticholesteremic Agents / Q000627:therapeutic use; D044466:Asian People / Q000235:genetics; D001384:Azetidines / Q000627:therapeutic use*; D002648:Child; D004252:DNA Mutational Analysis; D000069438:Ezetimibe; D005260:Female; D005820:Genetic Testing; D006801:Humans; D007223:Infant; D008074:Lipoproteins / Q000235:genetics*; D008661:Metabolism, Inborn Errors / Q000188:drug therapy* / Q000208:ethnology / Q000235:genetics*; D017354:Point Mutation; D012855:Sitosterols / Q000097:blood*
C416945:ABCG5 protein, human; D000071018:ATP Binding Cassette Transporter, Subfamily G, Member 5; D018528:ATP-Binding Cassette Transporters; D000924:Anticholesteremic Agents; D001384:Azetidines; D008074:Lipoproteins; D012855:Sitosterols; D000069438:Ezetimibe