Development of a new enzymatic diagnosis method for very-long-chain Acyl-CoA dehydrogenase deficiency by detecting 2-hexadecenoyl-CoA production and its application in tandem mass spectrometry-based selective screening and newborn screening in Japan.
Pediatr Res
; 64(6): 667-72, 2008 Dec.
Article
en En
| MEDLINE
| ID: mdl-18670371
ABSTRACT
The introduction of tandem mass spectrometry (MS/MS) has made it possible to screen for very-long-chain acyl-CoA dehydrogenase (VLCAD) deficiency. To confirm the diagnosis in cases with an abnormal profile of blood acylcarnitines, we developed a new enzymatic assay method for determining dehydrogenase activity toward palmitoyl-CoA (C160) in lymphocytes. Using this method, the production of 2-hexadecenoyl-CoA (C161) by crude cell lysates can be directly quantified using high performance liquid chromatography (HPLC). We applied the assay to 7 myopathic patients, 7 hypoglycemic patients, and 2 presymptomatic newborns with elevated levels of tetradecenoylcarnitine (C141 AC) in blood, and found impaired VLCAD activity in all of the 7 myopathic patients and both of the 2 newborns. All of the 7 hypoglycemic patients had normal level of the enzyme activity. Results of the ACADVL gene analysis were in consistent with the enzymatic diagnosis. These results suggest that MS/MS-based screening for VLCAD deficiency using blood C141 AC as the indicator may show a considerably high false-positive rate in selective screening of symptomatic patients. Our practical enzymatic assay can be a useful test for the accurate diagnosis of VLCAD deficiency cases screened by MS/MS.
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Acilcoenzima A
/
Tamizaje Neonatal
/
Acil-CoA Deshidrogenasa de Cadena Larga
/
Trastornos del Metabolismo de los Lípidos
/
Espectrometría de Masas en Tándem
Tipo de estudio:
Diagnostic_studies
/
Evaluation_studies
/
Screening_studies
Límite:
Adolescent
/
Adult
/
Child
/
Child, preschool
/
Female
/
Humans
/
Male
/
Newborn
País como asunto:
Asia
Idioma:
En
Año:
2008
Tipo del documento:
Article