3-Methylglutaconic Aciduria Type I Due to <i>AUH</i> Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature
3-Methylglutaconic aciduria type I (MGCA1) is an inborn error of the leucine degradation pathway caused by pathogenic variants in the <i>AUH</i> gene, which encodes 3-methylglutaconyl-coenzyme A hydratase (MGH). To date, MGCA1 has been diagnosed in 19 subjects and has been associated wit...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/8/4422 |
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| author | Francesca Nardecchia Anna Caciotti Teresa Giovanniello Sabrina De Leo Lorenzo Ferri Serena Galosi Silvia Santagata Barbara Torres Laura Bernardini Claudia Carducci Amelia Morrone Vincenzo Leuzzi |
| author_facet | Francesca Nardecchia Anna Caciotti Teresa Giovanniello Sabrina De Leo Lorenzo Ferri Serena Galosi Silvia Santagata Barbara Torres Laura Bernardini Claudia Carducci Amelia Morrone Vincenzo Leuzzi |
| author_sort | Francesca Nardecchia |
| collection | DOAJ |
| description | 3-Methylglutaconic aciduria type I (MGCA1) is an inborn error of the leucine degradation pathway caused by pathogenic variants in the <i>AUH</i> gene, which encodes 3-methylglutaconyl-coenzyme A hydratase (MGH). To date, MGCA1 has been diagnosed in 19 subjects and has been associated with a variable clinical picture, ranging from no symptoms to severe encephalopathy with basal ganglia involvement. We report the case of a 31-month-old female child referred to our center after the detection of increased 3-hydroxyisovalerylcarnitine levels at newborn screening, which were associated with increased urinary excretion of 3-methylglutaconic acid, 3-hydroxyisovaleric acid, and 3-methylglutaric acid. A next-generation sequencing (NGS) panel for 3-methylglutaconic aciduria failed to establish a definitive diagnosis. To further investigate the strong biochemical indication, we measured MGH activity, which was markedly decreased. Finally, single nucleotide polymorphism array analysis disclosed the presence of two microdeletions in compound heterozygosity encompassing the <i>AUH</i> gene, which confirmed the diagnosis. The patient was then supplemented with levocarnitine and protein intake was slowly decreased. At the last examination, the patient showed mild clumsiness and an expressive language disorder. This case exemplifies the importance of the biochemical phenotype in the differential diagnosis of metabolic diseases and the importance of collaboration between clinicians, biochemists, and geneticists for an accurate diagnosis. |
| first_indexed | 2024-03-09T13:32:17Z |
| format | Article |
| id | doaj.art-9ab4a702fd2348bd98c063567019ab90 |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T13:32:17Z |
| publishDate | 2022-04-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9ab4a702fd2348bd98c063567019ab902023-11-30T21:16:42ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-04-01238442210.3390/ijms230844223-Methylglutaconic Aciduria Type I Due to <i>AUH</i> Defect: The Case Report of a Diagnostic Odyssey and a Review of the LiteratureFrancesca Nardecchia0Anna Caciotti1Teresa Giovanniello2Sabrina De Leo3Lorenzo Ferri4Serena Galosi5Silvia Santagata6Barbara Torres7Laura Bernardini8Claudia Carducci9Amelia Morrone10Vincenzo Leuzzi11Department of Human Neuroscience, Sapienza University of Rome, 00185 Rome, ItalyLaboratory of Molecular Biology of Neurometabolic Diseases, Neuroscience Department, Meyer Children’s Hospital, 50139 Florence, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyDepartment of Translational and Precision Medicine, Sapienza University of Rome, 00161 Rome, ItalyLaboratory of Molecular Biology of Neurometabolic Diseases, Neuroscience Department, Meyer Children’s Hospital, 50139 Florence, ItalyDepartment of Human Neuroscience, Sapienza University of Rome, 00185 Rome, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyMedical Genetics Division, IRCCS Casa Sollievo della Sofferenza Foundation, 71013 San Giovanni Rotondo, ItalyMedical Genetics Division, IRCCS Casa Sollievo della Sofferenza Foundation, 71013 San Giovanni Rotondo, ItalyDepartment of Experimental Medicine, Sapienza University of Rome, 00161 Rome, ItalyLaboratory of Molecular Biology of Neurometabolic Diseases, Neuroscience Department, Meyer Children’s Hospital, 50139 Florence, ItalyDepartment of Human Neuroscience, Sapienza University of Rome, 00185 Rome, Italy3-Methylglutaconic aciduria type I (MGCA1) is an inborn error of the leucine degradation pathway caused by pathogenic variants in the <i>AUH</i> gene, which encodes 3-methylglutaconyl-coenzyme A hydratase (MGH). To date, MGCA1 has been diagnosed in 19 subjects and has been associated with a variable clinical picture, ranging from no symptoms to severe encephalopathy with basal ganglia involvement. We report the case of a 31-month-old female child referred to our center after the detection of increased 3-hydroxyisovalerylcarnitine levels at newborn screening, which were associated with increased urinary excretion of 3-methylglutaconic acid, 3-hydroxyisovaleric acid, and 3-methylglutaric acid. A next-generation sequencing (NGS) panel for 3-methylglutaconic aciduria failed to establish a definitive diagnosis. To further investigate the strong biochemical indication, we measured MGH activity, which was markedly decreased. Finally, single nucleotide polymorphism array analysis disclosed the presence of two microdeletions in compound heterozygosity encompassing the <i>AUH</i> gene, which confirmed the diagnosis. The patient was then supplemented with levocarnitine and protein intake was slowly decreased. At the last examination, the patient showed mild clumsiness and an expressive language disorder. This case exemplifies the importance of the biochemical phenotype in the differential diagnosis of metabolic diseases and the importance of collaboration between clinicians, biochemists, and geneticists for an accurate diagnosis.https://www.mdpi.com/1422-0067/23/8/44223-methylglutaconyl-coenzyme A hydratase (MGH) deficiency3-methylglutaconic aciduria type I<i>AUH</i> defect3-OH-isovalerylcarnitinenewborn screeningcase report |
| spellingShingle | Francesca Nardecchia Anna Caciotti Teresa Giovanniello Sabrina De Leo Lorenzo Ferri Serena Galosi Silvia Santagata Barbara Torres Laura Bernardini Claudia Carducci Amelia Morrone Vincenzo Leuzzi 3-Methylglutaconic Aciduria Type I Due to <i>AUH</i> Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature International Journal of Molecular Sciences 3-methylglutaconyl-coenzyme A hydratase (MGH) deficiency 3-methylglutaconic aciduria type I <i>AUH</i> defect 3-OH-isovalerylcarnitine newborn screening case report |
| title | 3-Methylglutaconic Aciduria Type I Due to <i>AUH</i> Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature |
| title_full | 3-Methylglutaconic Aciduria Type I Due to <i>AUH</i> Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature |
| title_fullStr | 3-Methylglutaconic Aciduria Type I Due to <i>AUH</i> Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature |
| title_full_unstemmed | 3-Methylglutaconic Aciduria Type I Due to <i>AUH</i> Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature |
| title_short | 3-Methylglutaconic Aciduria Type I Due to <i>AUH</i> Defect: The Case Report of a Diagnostic Odyssey and a Review of the Literature |
| title_sort | 3 methylglutaconic aciduria type i due to i auh i defect the case report of a diagnostic odyssey and a review of the literature |
| topic | 3-methylglutaconyl-coenzyme A hydratase (MGH) deficiency 3-methylglutaconic aciduria type I <i>AUH</i> defect 3-OH-isovalerylcarnitine newborn screening case report |
| url | https://www.mdpi.com/1422-0067/23/8/4422 |
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