Incorporating second-tier genetic screening for multiple acyl-CoA dehydrogenase deficiency.
Clin Chim Acta
; 537: 181-187, 2022 Dec 01.
Article
en En
| MEDLINE
| ID: mdl-36334790
ABSTRACT
BACKGROUND:
Newborn screening (NBS) for multiple acyl-CoA dehydrogenase deficiency (MADD) has poor sensitivity. This study aimed to evaluate the feasibility of incorporating second-tier genetic screening for MADD.METHODS:
A total of 453,390 newborns were screened for inherited metabolic disorders using tandem mass spectrometry from January 2017 to May 2022. A matrix-assisted laser desorption/ionization-time of flight mass spectrometry (MALDI-TOF MS) assay was developed to identify 23 common ETFDH variants and used for second-tier screening of MADD.RESULTS:
Overall, 185 newborns with suspected MADD received second-tier genetic screening. Thirty-three (17.8 %) newborns with positive results, of which 7 were homozygotes, 5 were compound heterozygotes, 21 were heterozygotes. Further genetic analysis revealed that 6 of the 21 newborns had a second ETFDH variant. Therefore, 18 patients were finally diagnosed with MADD, with a positive predictive value of 9.73 %. The detection rate and diagnostic rate of MALDI-TOF MS assay were 83.33 % and 66.67 %, respectively. Thus the incidence of MADD in our population was estimated at 125,188. Nine different ETFDH variants were identified in MADD patients. The most common ETFDH variant being c.250G > A with an allelic frequency of 47.22 %, followed by c.524G > A (13.89 %) and c.998A > G (13.89 %). All patients had elevation of multiple acylcarnitines at NBS. However, seven patients had normal acylcarnitine levels and two patients showed mild elevation of only two acylcarnitines during the recall review.CONCLUSION:
We have established a high throughput MALDI-TOF MS assay for MADD screening. Half of the MADD patients would not be detected under conventional screening protocols. Incorporating second-tier genetic screening into the current NBS could improve the performance of MADD NBS.Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Deficiencia Múltiple de Acil Coenzima A Deshidrogenasa
/
Oxidorreductasas actuantes sobre Donantes de Grupo CH-NH
/
Proteínas Hierro-Azufre
Tipo de estudio:
Diagnostic_studies
/
Guideline
/
Prognostic_studies
/
Screening_studies
Límite:
Humans
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Newborn
Idioma:
En
Revista:
Clin Chim Acta
Año:
2022
Tipo del documento:
Article
País de afiliación:
China