title: Newborn population screening for classic homocystinuria by determination of total homocysteine from Guthrie cards.
abstract: OBJECTIVE
  To allow early recognition of cystathionine beta-synthase by newborn screening.
  
  
  METHODS
  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.
authors.affiliation: Department of Pediatrics, Ruprecht-Karls-University, Heidelberg, Germany.
authors.forename: Hongying
authors.initials: H
authors.lastname: Gan-Schreier
authors.forename: Moustafa
authors.initials: M
authors.lastname: Kebbewar
authors.forename: Junmin
authors.initials: J
authors.lastname: Fang-Hoffmann
authors.forename: Julia
authors.initials: J
authors.lastname: Wilrich
authors.forename: Ghassan
authors.initials: G
authors.lastname: Abdoh
authors.forename: Tawfeg
authors.initials: T
authors.lastname: Ben-Omran
authors.forename: Noora
authors.initials: N
authors.lastname: Shahbek
authors.forename: Abdulbari
authors.initials: A
authors.lastname: Bener
authors.forename: Hilal
authors.initials: H
authors.lastname: Al Rifai
authors.forename: Abdul Latif
authors.initials: AL
authors.lastname: Al Khal
authors.forename: Martin
authors.initials: M
authors.lastname: Lindner
authors.forename: Johannes
authors.initials: J
authors.lastname: Zschocke
authors.forename: Georg F
authors.initials: GF
authors.lastname: Hoffmann
mesh_terms: D002851:Chromatography, High Pressure Liquid; D003541:Cystathionine beta-Synthase / Q000235:genetics; D004252:DNA Mutational Analysis; D006579:Heterozygote; D006710:Homocysteine / Q000097:blood*; D006712:Homocystinuria / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D008715:Methionine / Q000097:blood; D015997:Neonatal Screening; D011780:Qatar / Q000453:epidemiology; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry
chemical_list: D006710:Homocysteine; D008715:Methionine; D003541:Cystathionine beta-Synthase