ABCMdb

ABCG5 p.Tyr329*

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[hide] Clinical observations, molecular genetic analysis,... J Inherit Metab Dis. 2010 Aug;33(4):437-43. Epub 2010 Jun 3. Niu DM, Chong KW, Hsu JH, Wu TJ, Yu HC, Huang CH, Lo MY, Kwok CF, Kratz LE, Ho LT
Clinical observations, molecular genetic analysis, and treatment of sitosterolemia in infants and children.
J Inherit Metab Dis. 2010 Aug;33(4):437-43. Epub 2010 Jun 3., [PMID:20521169]

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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.

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No. Sentence Comment
1 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. Login to comment
23 Large peaks of serum plant sterols were identified by nuclear magnetic resonance (NMR) spectroscopy, but the exact concentrations of these sterols were unable to be Table 1 Baseline lipid profiles, liver enzymes, and blood cell counts of each study patient Patient no Normal values 1 2 3 4 5 Age at diagnosis 8 years 18 months 3 months 23 months 12 years Mutation (ABCG5) Y329X R389H R389H R389H R389H N437K R446X R446X R389H G269R Initial diagnostic data Cholesterol, mg/dl Total 125-240 427 705 402 640 343 Low-density-lipoprotein 60-150 346 565 304 519 263 High-density-lipoprotein 35-84 59 64 42 64 50 Total triglycerides, mg/dl 20-200 111 149 395a 98 98 Liver enzymes Alanine transaminase, U/l 5-45 10 13 45 15 44 Aspartate aminotransferase, U/l 15-55 19 31 100 31 37 Blood count Erythrocytes, count/µl 3.7×109 -5.3×109 3.35×109 4.25×109 3.98×109 4.49×109 4.46×109 Hemoglobin, g/dl 11.5-15.5 9.8 11.8 11 12.7 12.9 Mean corpuscular volume, fl 80-95 88.5 89.0 80.6 80.2 86 White blood cells, count/µl 4,500-17,500 7,200 6,900 6,700 11,200 5,200 Platelets, count/mm3 150×106 -350×106 211×106 289×106 506×106 566×106 293×106 After ezetimibe therapy Age at plant sterols analysis NA 5 years 3 years 3 year 13 year Duration of ezetimibe treatment NA 3 years 1 year 1 year 6 months Cholesterol, total (mg/dl) 125-240 NA 181 208 223 193 Sitosterol mg/dlb 0.216±0.220 (SD)c NA 7.10 9.17 7.07 6.14 Campesterol mg/dlb 0.309±0.165 (SD)c NA 3.79 4.78 4.04 4.22 NA not available a In the nonfasting state b Plant sterols were measured by gas chromatography/mass spectrometry, as previously described (Kwiterovich et al. 2003). Login to comment
75 Results of mutation analyses Patient 1 had compound heterozygous mutations, p.Y329X and p.N437K. Login to comment
76 The new mutation, p.Y329X (c.987C>A), located in exon 8, substituted an amino acid codon (tyrosine) to a stop codon at codon 329. Login to comment