Newborn population screening for classic homocystinuria by determination of total homocysteine from Guthrie cards.
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.
Gan-Schreier
Hongying
H
Department of Pediatrics, Ruprecht-Karls-University, Heidelberg, Germany.
Kebbewar
Moustafa
M
Fang-Hoffmann
Junmin
J
Wilrich
Julia
J
Abdoh
Ghassan
G
Ben-Omran
Tawfeg
T
Shahbek
Noora
N
Bener
Abdulbari
A
Al Rifai
Hilal
H
Al Khal
Abdul Latif
AL
Lindner
Martin
M
Zschocke
Johannes
J
Hoffmann
Georg F
GF
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
D006710:Homocysteine; D008715:Methionine; D003541:Cystathionine beta-Synthase