Relation between biomarkers and clinical severity in patients with Smith-Lemli-Opitz syndrome

Anna V. Oláh, Gabriella P. Szabó, József Varga, Lídia Balogh, Györgyi Csábi, Violetta Csákváry, Wolfgang Erwa, István Balogh

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Abstract

Smith-Lemli-Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n=4, clinical score 20) was 0.5-18 years, cholesterol was 2.37±0.8 mmol/L, and 7DHC was 0.38± 0.14 mmol/L. In the group of typical SLOS (n=7, score 20-50), the diagnosis was set up earlier (age of 0.1-7 years); t-cholesterol was 1.47±0.7 mmol/L, and 7DHC was 0.53± 0.20 mmol/L. Patients with severe SLOS (n=4, clinical score50) died as newborns and had the lowest t-cholesterol (0.66±0.27 mmol/L), and 7DHC was 0.47±0.14 mmol/L. Correlation coefficient with clinical severity was 0.74 for initial t-cholesterol and 0.669 for Cho/7DHC. Statistically significant difference was between the initial t-cholesterol of mild and severe SLOS (p=0.01), and between the Cho/7DHC ratios of groups (p=0.004). In severe SLOS, the percentage of α-lipoprotein was significantly lower than in typical (p=0.003) and mild SLOS (p=0.004). Although serum albumin, total bilirubin, and hemostasis parameters remained in the reference range during cholesterol supplementation (n=10) combined with statin therapy (n=9), increase of aspartate aminotransfer-ase and alanine aminotransferase in 50 % of the patients probably refers to a reversible alteration of liver function; therefore, statin therapy was suspended. Conclusion: life expectancy is fundamentally determined by the initial t-cholesterol, but dehydrocholesterol and α-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of α-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.

Original languageEnglish
Pages (from-to)623-630
Number of pages8
JournalEuropean Journal of Pediatrics
Volume172
Issue number5
DOIs
Publication statusPublished - May 2013

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Smith-Lemli-Opitz Syndrome
Biomarkers
Cholesterol
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Lipoproteins
Dehydrocholesterols
Liver
Genetic Testing
Life Expectancy
Hemostasis
Alanine Transaminase
Bilirubin
Aspartic Acid
Serum Albumin
Intellectual Disability
Molecular Biology
Reference Values
Therapeutics
Newborn Infant
Lipids

Keywords

  • 7-Dehydrocholesterol
  • Cholesterol
  • Lipoprotein electrophoresis
  • Liver function
  • Smith-Lemli-Opitz syndrome
  • Statin

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health

Cite this

Relation between biomarkers and clinical severity in patients with Smith-Lemli-Opitz syndrome. / Oláh, Anna V.; Szabó, Gabriella P.; Varga, József; Balogh, Lídia; Csábi, Györgyi; Csákváry, Violetta; Erwa, Wolfgang; Balogh, István.

In: European Journal of Pediatrics, Vol. 172, No. 5, 05.2013, p. 623-630.

Research output: Contribution to journalArticle

Oláh, Anna V. ; Szabó, Gabriella P. ; Varga, József ; Balogh, Lídia ; Csábi, Györgyi ; Csákváry, Violetta ; Erwa, Wolfgang ; Balogh, István. / Relation between biomarkers and clinical severity in patients with Smith-Lemli-Opitz syndrome. In: European Journal of Pediatrics. 2013 ; Vol. 172, No. 5. pp. 623-630.
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abstract = "Smith-Lemli-Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n=4, clinical score 20) was 0.5-18 years, cholesterol was 2.37±0.8 mmol/L, and 7DHC was 0.38± 0.14 mmol/L. In the group of typical SLOS (n=7, score 20-50), the diagnosis was set up earlier (age of 0.1-7 years); t-cholesterol was 1.47±0.7 mmol/L, and 7DHC was 0.53± 0.20 mmol/L. Patients with severe SLOS (n=4, clinical score50) died as newborns and had the lowest t-cholesterol (0.66±0.27 mmol/L), and 7DHC was 0.47±0.14 mmol/L. Correlation coefficient with clinical severity was 0.74 for initial t-cholesterol and 0.669 for Cho/7DHC. Statistically significant difference was between the initial t-cholesterol of mild and severe SLOS (p=0.01), and between the Cho/7DHC ratios of groups (p=0.004). In severe SLOS, the percentage of α-lipoprotein was significantly lower than in typical (p=0.003) and mild SLOS (p=0.004). Although serum albumin, total bilirubin, and hemostasis parameters remained in the reference range during cholesterol supplementation (n=10) combined with statin therapy (n=9), increase of aspartate aminotransfer-ase and alanine aminotransferase in 50 {\%} of the patients probably refers to a reversible alteration of liver function; therefore, statin therapy was suspended. Conclusion: life expectancy is fundamentally determined by the initial t-cholesterol, but dehydrocholesterol and α-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of α-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.",
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AU - Varga, József

AU - Balogh, Lídia

AU - Csábi, Györgyi

AU - Csákváry, Violetta

AU - Erwa, Wolfgang

AU - Balogh, István

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N2 - Smith-Lemli-Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n=4, clinical score 20) was 0.5-18 years, cholesterol was 2.37±0.8 mmol/L, and 7DHC was 0.38± 0.14 mmol/L. In the group of typical SLOS (n=7, score 20-50), the diagnosis was set up earlier (age of 0.1-7 years); t-cholesterol was 1.47±0.7 mmol/L, and 7DHC was 0.53± 0.20 mmol/L. Patients with severe SLOS (n=4, clinical score50) died as newborns and had the lowest t-cholesterol (0.66±0.27 mmol/L), and 7DHC was 0.47±0.14 mmol/L. Correlation coefficient with clinical severity was 0.74 for initial t-cholesterol and 0.669 for Cho/7DHC. Statistically significant difference was between the initial t-cholesterol of mild and severe SLOS (p=0.01), and between the Cho/7DHC ratios of groups (p=0.004). In severe SLOS, the percentage of α-lipoprotein was significantly lower than in typical (p=0.003) and mild SLOS (p=0.004). Although serum albumin, total bilirubin, and hemostasis parameters remained in the reference range during cholesterol supplementation (n=10) combined with statin therapy (n=9), increase of aspartate aminotransfer-ase and alanine aminotransferase in 50 % of the patients probably refers to a reversible alteration of liver function; therefore, statin therapy was suspended. Conclusion: life expectancy is fundamentally determined by the initial t-cholesterol, but dehydrocholesterol and α-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of α-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.

AB - Smith-Lemli-Opitz syndrome (SLOS), a multiple congenital anomaly with severe mental retardation, is caused by decreased activity of 7-dehydrocholesterol reductase. Fifteen Hungarian patients were diagnosed with SLOS on the basis of clinical symptoms, serum cholesterol, 7-dehydrocholesterol, and molecular genetic testing. Their age at the time of diagnosis in mild SLOS (n=4, clinical score 20) was 0.5-18 years, cholesterol was 2.37±0.8 mmol/L, and 7DHC was 0.38± 0.14 mmol/L. In the group of typical SLOS (n=7, score 20-50), the diagnosis was set up earlier (age of 0.1-7 years); t-cholesterol was 1.47±0.7 mmol/L, and 7DHC was 0.53± 0.20 mmol/L. Patients with severe SLOS (n=4, clinical score50) died as newborns and had the lowest t-cholesterol (0.66±0.27 mmol/L), and 7DHC was 0.47±0.14 mmol/L. Correlation coefficient with clinical severity was 0.74 for initial t-cholesterol and 0.669 for Cho/7DHC. Statistically significant difference was between the initial t-cholesterol of mild and severe SLOS (p=0.01), and between the Cho/7DHC ratios of groups (p=0.004). In severe SLOS, the percentage of α-lipoprotein was significantly lower than in typical (p=0.003) and mild SLOS (p=0.004). Although serum albumin, total bilirubin, and hemostasis parameters remained in the reference range during cholesterol supplementation (n=10) combined with statin therapy (n=9), increase of aspartate aminotransfer-ase and alanine aminotransferase in 50 % of the patients probably refers to a reversible alteration of liver function; therefore, statin therapy was suspended. Conclusion: life expectancy is fundamentally determined by the initial t-cholesterol, but dehydrocholesterol and α-lipoprotein have prognostic value. Accumulation of hepatotoxic DHC may inhibit the synthesis of α-lipoproteins, decreasing the reverse cholesterol transport. During statin therapy, we suggest monitoring of lipid parameters and liver function.

KW - 7-Dehydrocholesterol

KW - Cholesterol

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KW - Liver function

KW - Smith-Lemli-Opitz syndrome

KW - Statin

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