Value of amniotic fluid homocysteine assay in prenatal diagnosis of combined methylmalonic acidemia and homocystinuria, cobalamin C type

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چکیده

Abstract Background Combined methylmalonic acidemia and homocystinuria, cobalamin C type (cblC defect) is the most common inborn error of metabolism, different approaches have been applied to its prenatal diagnosis. To evaluate reliability biochemical method for diagnosis cblC defect, we conducted a retrospective study our 10-year experience at single center. Methods 248 pregnancies whose probands were diagnosed as defect referred center from January 2010 December 2019. Prenatal data Hcy levels determined by enzymatic cycling assay, acylcarnitine analysis using liquid chromatography tandem mass spectrometry, organic acid gas genetic direct sequencing at-risk fetuses retrospectively reviewed. Results For 2.0 16.0 μmol/L AF samples, relative errors − 2.5% 2.8%, respectively. The respective measurement uncertainties 13.07% 14.20%. fetuses, 63 affected 185 unaffected. level 13.20 (6.62–43.30) in was significantly higher than that unaffected 2.70 (0.00–5.80) μmol/L, there no overlap between groups. diagnostic sensitivity specificity 100% 92.05%, positive negative predictive values combination Hcy, propionylcarnitine (C3), ratio C3 acetylcarnitine (C2; C3/C2), (MMA), methylcitric (MCA) both 100%. Sixteen displayed inconclusive results MMACHC variants, which seven be with elevated C3, C3/C2 MMA, their 18.50 (6.70–43.30) 8.53(5.02–11.91) 0.77 (0.52–0.97), 8.96 (6.55–40.32) mmol/mol Cr, remaining nine considered based on normal amniotic fluid metabolite profile. Conclusions appears another characteristic biomarker defect. assay fast, sensitive, reliable approach. This approach could overcome challenge lack families fetuses.

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ژورنال

عنوان ژورنال: Orphanet Journal of Rare Diseases

سال: 2021

ISSN: ['1750-1172']

DOI: https://doi.org/10.1186/s13023-021-01762-z