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. 2000 Jun;82(6):490–492. doi: 10.1136/adc.82.6.490

Diagnosis of Smith-Lemli-Opitz syndrome from stored filter paper blood specimens

L Starck 1, A Lovgren 1
PMCID: PMC1718355  PMID: 10833186

Abstract

BACKGROUND—Smith-Lemli-Opitz (SLO) syndrome is a recessively inheritable metabolic disease with deficiency of cholesterol and accumulation of dehydrocholesterols, caused by a defect in the last step of cholesterol biosynthesis. Biochemical methods for identification of affected individuals, even prenatally, have been developed. Reliable genetic counselling is now possible.
AIM—To find a method of proving or disproving whether a child in whom SLO syndrome had been suspected but not confirmed during lifetime had in fact died of the SLO syndrome.
METHODS—Lipid extracts of stored filter paper blood specimens collected at the national neonatal metabolic screening were used. The ratio of dehydrocholesterols to cholesterol was measured by combined gas chromatography-mass spectrometry.
RESULTS—The ratio of 8-dehydrocholesterol to cholesterol in stored filter paper specimens clearly distinguished affected infants from normal infants. SLO syndrome was thus proven in two children who had died more than seven years earlier.
CONCLUSION—It is possible to diagnose SLO syndrome from dried paper specimens, even when the samples were collected more than a decade ago. Genetic counselling is available for families of affected children who died before the discovery of the defect in cholesterol synthesis.



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Selected References

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  1. Cunniff C., Kratz L. E., Moser A., Natowicz M. R., Kelley R. I. Clinical and biochemical spectrum of patients with RSH/Smith-Lemli-Opitz syndrome and abnormal cholesterol metabolism. Am J Med Genet. 1997 Jan 31;68(3):263–269. [PubMed] [Google Scholar]
  2. Elias E. R., Irons M. B., Hurley A. D., Tint G. S., Salen G. Clinical effects of cholesterol supplementation in six patients with the Smith-Lemli-Opitz syndrome (SLOS) Am J Med Genet. 1997 Jan 31;68(3):305–310. doi: 10.1002/(sici)1096-8628(19970131)68:3<305::aid-ajmg11>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]
  3. Gustafsson J., Sisfontes L., Björkhem I. Diagnosis of Zellweger syndrome by analysis of bile acids and plasmalogens in stored dried blood collected at neonatal screening. J Pediatr. 1987 Aug;111(2):264–267. doi: 10.1016/s0022-3476(87)80084-7. [DOI] [PubMed] [Google Scholar]
  4. Irons M. B., Tint G. S. Prenatal diagnosis of Smith-Lemli-Opitz syndrome. Prenat Diagn. 1998 Apr;18(4):369–372. [PubMed] [Google Scholar]
  5. MAKITA M., WELLS W. W. Quantitative analysis of fecal bile acids by gas-liquid chromatography. Anal Biochem. 1963 Jun;5:523–530. doi: 10.1016/0003-2697(63)90072-1. [DOI] [PubMed] [Google Scholar]
  6. Opitz J. M. RSH/SLO ("Smith-Lemli-Opitz") syndrome: historical, genetic, and developmental considerations. Am J Med Genet. 1994 May 1;50(4):344–346. doi: 10.1002/ajmg.1320500408. [DOI] [PubMed] [Google Scholar]
  7. Ryan A. K., Bartlett K., Clayton P., Eaton S., Mills L., Donnai D., Winter R. M., Burn J. Smith-Lemli-Opitz syndrome: a variable clinical and biochemical phenotype. J Med Genet. 1998 Jul;35(7):558–565. doi: 10.1136/jmg.35.7.558. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. SMITH D. W., LEMLI L., OPITZ J. M. A NEWLY RECOGNIZED SYNDROME OF MULTIPLE CONGENITAL ANOMALIES. J Pediatr. 1964 Feb;64:210–217. doi: 10.1016/s0022-3476(64)80264-x. [DOI] [PubMed] [Google Scholar]
  9. Salen G., Shefer S., Batta A. K., Tint G. S., Xu G., Honda A., Irons M., Elias E. R. Abnormal cholesterol biosynthesis in the Smith-Lemli-Opitz syndrome. J Lipid Res. 1996 Jun;37(6):1169–1180. [PubMed] [Google Scholar]
  10. Starck L., Björkhem I., Ritzén E. M., Nilsson B. Y., von Döbeln U. Beneficial effects of dietary supplementation in a disorder with defective synthesis of cholesterol. A case report of a girl with Smith-Lemli-Opitz syndrome, polyneuropathy and precocious puberty. Acta Paediatr. 1999 Jul;88(7):729–733. doi: 10.1080/08035259950169008. [DOI] [PubMed] [Google Scholar]
  11. Tint G. S., Irons M., Elias E. R., Batta A. K., Frieden R., Chen T. S., Salen G. Defective cholesterol biosynthesis associated with the Smith-Lemli-Opitz syndrome. N Engl J Med. 1994 Jan 13;330(2):107–113. doi: 10.1056/NEJM199401133300205. [DOI] [PubMed] [Google Scholar]
  12. Zimmerman P. A., Hercules D. M., Naylor E. W. Direct analysis of filter paper blood specimens for identification of Smith-Lemli-Opitz syndrome using time-of-flight secondary ion mass spectrometry. Am J Med Genet. 1997 Jan 31;68(3):300–304. doi: 10.1002/(sici)1096-8628(19970131)68:3<300::aid-ajmg10>3.0.co;2-x. [DOI] [PubMed] [Google Scholar]

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