Newborn population screening for classic homocystinuria by determination of total homocysteine from Guthrie cards

J Pediatr. 2010 Mar;156(3):427-32. doi: 10.1016/j.jpeds.2009.09.054. Epub 2009 Nov 14.


Objective: To allow early recognition of cystathionine beta-synthase by newborn screening.

Study design: Total homocysteine was determined in dried blood spots with a novel, robust high-performance liquid chromatography method with tandem mass spectrometry. Quantification of homocysteine was linear over a working range up to 50 micromol/L. For mutation analysis, DNA was tested for 2 mutations common in Qatar.

Results: Both methods proved to be suitable for high throughput processing. In 2 years, 7 infants with classic homocystinuria were identified of 12,603 native Qatari infants, yielding an incidence of 1:1800. Molecular screening would have missed 1 patient homozygous for a mutation not previously identified in the Qatari population. Over a period of 3 years, a total of 14 cases of classic homocystinuria were detected by screening of homocysteine from all newborn infants born in Qatar (n = 46 406). Homocysteine was always elevated, whereas methionine was elevated in only 7 cases.

Conclusions: The study offers a reliable method for newborn screening for cystathionine beta-synthase deficiency, reaching a sensitivity of up to 100%, even if samples are taken within the first 3 days of life.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Chromatography, High Pressure Liquid
  • Cystathionine beta-Synthase / genetics
  • DNA Mutational Analysis
  • Heterozygote
  • Homocysteine / blood*
  • Homocystinuria / diagnosis*
  • Homocystinuria / epidemiology
  • Homocystinuria / genetics
  • Homozygote
  • Humans
  • Infant, Newborn
  • Methionine / blood
  • Neonatal Screening*
  • Qatar / epidemiology
  • Sensitivity and Specificity
  • Tandem Mass Spectrometry


  • Homocysteine
  • Methionine
  • Cystathionine beta-Synthase