Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report
Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it...
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2024-07-01
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| Series: | International Journal of Neonatal Screening |
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| author | Evelina Maines Roberto Franceschi Francesca Rivieri Giovanni Piccoli Björn Schulte Jessica Hoffmann Andrea Bordugo Giulia Rodella Francesca Teofoli Monica Vincenzi Massimo Soffiati Marta Camilot |
| author_facet | Evelina Maines Roberto Franceschi Francesca Rivieri Giovanni Piccoli Björn Schulte Jessica Hoffmann Andrea Bordugo Giulia Rodella Francesca Teofoli Monica Vincenzi Massimo Soffiati Marta Camilot |
| author_sort | Evelina Maines |
| collection | DOAJ |
| description | Methylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be incidentally identified when investigating methylmalonic acidemia and propionic acidemia. Here, we report for the first time the biochemical description of a case detected by NBS. The NBS results showed increased levels of propionylcarnitine (C3) and 2-methylcitric acid (MCA), while methylmalonic acid (MMA) and homocysteine (Hcy) were within the reference limits. Confirmatory analyses revealed altered levels of metabolites, including MCA and MMA, suggesting a block in the propionate degradation pathway. The analysis of methylmalonic pathway genes by next-generation sequencing (NGS) allowed the identification of the known homozygous nonsense variation c.139C>T (p.R47X) in exon 2 of the MCE gene. Conclusions: Elevated concentrations of C3 with a slight increase in MCA and normal MMA and Hcy during NBS should prompt the consideration of MCEE deficiency in differential diagnosis. Increased MMA levels may be negligible at NBS as they may reach relevant values beyond the first days of life and thus could be identified only in confirmatory analyses. |
| format | Article |
| id | doaj-art-b60cffae35ee45fc8e6900dc66977123 |
| institution | Kabale University |
| issn | 2409-515X |
| language | English |
| publishDate | 2024-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Neonatal Screening |
| spelling | doaj-art-b60cffae35ee45fc8e6900dc669771232025-02-07T14:48:36ZengMDPI AGInternational Journal of Neonatal Screening2409-515X2024-07-011035310.3390/ijns10030053Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case ReportEvelina Maines0Roberto Franceschi1Francesca Rivieri2Giovanni Piccoli3Björn Schulte4Jessica Hoffmann5Andrea Bordugo6Giulia Rodella7Francesca Teofoli8Monica Vincenzi9Massimo Soffiati10Marta Camilot11Division of Pediatrics, Santa Chiara General Hospital, APSS Trento, 38122 Trento, ItalyDivision of Pediatrics, Santa Chiara General Hospital, APSS Trento, 38122 Trento, ItalyGenetic Unit, Laboratory of Clinical Pathology, Department of Laboratories, APSS Trento, 38122 Trento, ItalyCIBIO—Department of Cellular, Computational and Integrative Biology, Università degli Studi di Trento, 38122 Trento, ItalyCeGaT GmbH Tuebingen, 72076 Tuebingen, GermanyCeGaT GmbH Tuebingen, 72076 Tuebingen, GermanyInherited Metabolic Disease Unit, Pediatric Department, AOUI Verona, 37134 Verona, ItalyInherited Metabolic Disease Unit, Pediatric Department, AOUI Verona, 37134 Verona, ItalyDepartment of Mother and Child, The Regional Center for Neonatal Screening, Diagnosis and Treatment of Inherited Congenital Metabolic and Endocrinological Diseases, AOUI Verona, 37134 Verona, ItalyDepartment of Mother and Child, The Regional Center for Neonatal Screening, Diagnosis and Treatment of Inherited Congenital Metabolic and Endocrinological Diseases, AOUI Verona, 37134 Verona, ItalyDivision of Pediatrics, Santa Chiara General Hospital, APSS Trento, 38122 Trento, ItalyDepartment of Mother and Child, The Regional Center for Neonatal Screening, Diagnosis and Treatment of Inherited Congenital Metabolic and Endocrinological Diseases, AOUI Verona, 37134 Verona, ItalyMethylmalonyl-CoA epimerase enzyme (MCEE) is responsible for catalyzing the isomeric conversion between D- and L-methylmalonyl-CoA, an intermediate along the conversion of propionyl-CoA to succinyl-CoA. A dedicated test for MCEE deficiency is not included in the newborn screening (NBS) panels but it can be incidentally identified when investigating methylmalonic acidemia and propionic acidemia. Here, we report for the first time the biochemical description of a case detected by NBS. The NBS results showed increased levels of propionylcarnitine (C3) and 2-methylcitric acid (MCA), while methylmalonic acid (MMA) and homocysteine (Hcy) were within the reference limits. Confirmatory analyses revealed altered levels of metabolites, including MCA and MMA, suggesting a block in the propionate degradation pathway. The analysis of methylmalonic pathway genes by next-generation sequencing (NGS) allowed the identification of the known homozygous nonsense variation c.139C>T (p.R47X) in exon 2 of the MCE gene. Conclusions: Elevated concentrations of C3 with a slight increase in MCA and normal MMA and Hcy during NBS should prompt the consideration of MCEE deficiency in differential diagnosis. Increased MMA levels may be negligible at NBS as they may reach relevant values beyond the first days of life and thus could be identified only in confirmatory analyses.https://www.mdpi.com/2409-515X/10/3/53methylmalonyl CoA epimerase deficiencynewborn screeningcase report |
| spellingShingle | Evelina Maines Roberto Franceschi Francesca Rivieri Giovanni Piccoli Björn Schulte Jessica Hoffmann Andrea Bordugo Giulia Rodella Francesca Teofoli Monica Vincenzi Massimo Soffiati Marta Camilot Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report International Journal of Neonatal Screening methylmalonyl CoA epimerase deficiency newborn screening case report |
| title | Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report |
| title_full | Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report |
| title_fullStr | Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report |
| title_full_unstemmed | Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report |
| title_short | Biochemical Pattern of Methylmalonyl-CoA Epimerase Deficiency Identified in Newborn Screening: A Case Report |
| title_sort | biochemical pattern of methylmalonyl coa epimerase deficiency identified in newborn screening a case report |
| topic | methylmalonyl CoA epimerase deficiency newborn screening case report |
| url | https://www.mdpi.com/2409-515X/10/3/53 |
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