A case of Smith-Lemli-Opitz syndrome diagnosed by identification of mutations in the 7-dehydrocholesterol reductase (DHCR7) gene / 소아과

Smith-Lemli-Opitz syndrome (SLOS) is a rare, autosomal recessive disease caused by an inborn error in cholesterol synthesis. Patients with this disease suffer from multiple malformations due to reduced activity of 7-dehydrocholesterol reductase (DHCR7), which increases 7-dehydrocholesterol (7DHC) and 8-dehydrocholesterol (8DHC) concentrations and decreases cholesterol concentration in body fluids and tissue. The SLOS phenotypic spectrum ranges from a mild disorder with behavioral and learning problems to a lethal disease characterized by multiple malformations. Here, we describe a newborn male with ambiguous genitalia who was diagnosed to have type II SLOS during the neonatal period. A clinical examination revealed low levels of unconjugated estriol in the maternal serum, and a variety of fetal ultrasound anomalies, including prenatal growth retardation. After birth, the infant was diagnosed to have congenital heart disease (Tetralogy of Fallot with severe pulmonary artery stenosis), cleft lip and palate, micrognathia, postaxial polydactyly, ambiguous genitalia, and cataracts. Clinical investigation revealed extremely low plasma cholesterol levels and the presence of mutation (homozygote of p.Arg352Gln) in the DHCR7 gene. The patient underwent palliative heart surgery (to widen the pulmonary artery) and received intravenous lipid supplementation. Cholesterol levels increased slightly, but not to normal values. The patient died from cardiopulmonary failure and sepsis 72 days after birth. This report provides the first description of a Korean patient with SLOS confirmed by verification of DHCR7 gene mutation and illustrates the need for early recognition and appropriate diagnosis of this disease.

Oxysterol (3,5-cholestadien-7-one, 5beta-cholestan-3-one, 5,24-cholestadien-3beta-OL) Induced Cytotoxicity and Apoptosis in Gallbladder Epithelial Cells / 대한소화기학회지

BACKGROUND/AIMS: Biliary epithelial cells are exposed to highly concentrated oxysterols. Therefore, oxysterols may play a role in pathogenesis of biliary tract diseases. We investigated the cytotoxic effect and apoptosis inducing effect of oxysterol on gallbladder epithelial cells. METHODS: We studied the cytotoxic effect of 3,5- cholestadien-7-one, 5beta-cholestan-3-one and 5,24-cholestadien-3beta-OL which are identified in human bile and pigment gallstones on dog gallbladder epithelial cells (DGBE) and mouse gallbladder epithelial cells (MGBE). We used model bile to dissolve oxysterols as in vitro experiment and also used MTT, cell count, Diff-Quick stain, and flow cytometry to investigate cytotoxicity and apoptosis. RESULTS: Oxysterols dissolved in model bile have cytotoxic effects in a dose dependent fashion. In oxysterol containing model bile, viable cells are 51% in 500 microM 5beta-cholestan-3-one (cholesterol : oxysterol 50:50) and 47% in 5 mM 3,5-cholestadien-7-one (90:10) on MGBE, and are 129% and 38% in 500 microM (50:50) 3,5-cholestadien-7-one and 5beta-cholestan-3-one on DGBE, and are 74% and 71.5% in 5 mM (90:10) 3,5-cholestadien-7-one and 5beta-cholestan-3-one on DGBE, respectively. 500 microM (50:50) 3,5- cholestadien-7-one, 5beta-cholestan-3-one, and 5,24-cholestadien-3beta-OL treated on DGBE increase the apoptotic cell number as 22.0+/-8.8, 30.2+/-12.6, and 45.5+/-13.2%, respectively, compared with control (14.6+/-10.0%). 500 microM (50:50) 3,5-cholestadien-7-one, 5beta-cholestan-3-one, and 5,24-cholestadien-3beta-OL also affect the changes in cell cycles compared with the control. CONCLUSIONS: We concluded that oxysterol containing model bile is useful as an in vitro experiment as model to analyze the effects of oxysterols on biliary epithelial cells and that adequate concentration of oxysterols can induce the cytotoxic effect and the apoptosis on gallbladder epithelial cells.

Does gender confound risk factors for actue under 40 years of age? a case control study

Studies have shown that gender has an effect on acute myocardial infarction [AMI]. The current study concentrated on those under 40 years of age. Little research has been done on this age group in Iraq. The effect of gender on fatality due to AMI was studied. In addition, the confounding effect of gender on known risk factors was studied. to assess the effect of gender on risk factors of AMI in patients under 40 years of age. a case control study was conducted in Ibn Al Nafis Cardiology Hospital in Baghdad during the period from May to December 2000. All cases of AMI 40 years of age and under were studied. A total of 48 cases, 40 males and 8 females were admitted to the hospital and included in the study. Cases were diagnosed as AMI only with ECG changes and/or enzyme changes suggestive of the disease. Both typical and atypical histories were included. A control group was selected from the outpatient department of the same hospital. The controls were matched with the cases as closely as possible in terms of age and sex. AMI was excluded in the controls using the same criteria. An interview of all cases and controls using a validated questionnaire was carried out. Main Outcome Measures included distribution of cases compared to controls in terms of age and gender. Case fatality by gender was studied. The effect of gender was measured on the risk factors studied. males were more affected in the younger age group than females. Increasing age, in general, was found to have a positive correlation with the number of cases admitted [Pearson's rho=0.943, p=0.057]. Younger age group seemed to have a protective effect against fatal outcome of the disease. Current smoking was found to have a significant effect unconfounded by gender [adjusted Mantel- Haenszel weighted OR=3.3 with a 95% confidence limits of 1.16-9.63]. High serum cholesterol [>250 mg/dl] showed a significant effect unconfounded by gender [OR=7.93, 95% confidence interval 1.73-62.04]. Low density lipoproteins [LDL] showed significantly higher values in cases compared to controls [F=11.29, p=0.0001], and high density lipoproteins [HDL] showed significantly lower values in cases [F value=2.67, p=0.023]. In both LDL/HDL and the total cholesterol TC/HDL ratios, the cases showed significantly higher values than the controls [F value = 8.51 and 4.91 respectively, p value=<0.0001 for both]. Family history was unconfounded by gender. [Adjusted OR = 3.76, 95% CI 1.18-12.86]. fatality associated with AMI in those under 40 years of age affected males more than females. Gender did not appear to confound risk factors for AMI including current smoking, high cholesterol levels, high levels of LDL, low levels of HDL, and family history. These are important risk factors in patients under 40 years of age irrespective of gender