The value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia
Abstract Tetrahydrobiopterin deficiency in newborns with atypical hyperphenylalaninemia requires rapid and accurate diagnosis and the ability to distinguish it from the classical type to prevent early irreversible neurological damage. The study aimed to evaluate neopterin and biopterin (products of...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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SpringerOpen
2024-01-01
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| Series: | Egyptian Liver Journal |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s43066-024-00312-z |
| _version_ | 1797350118666534912 |
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| author | Nadia Salama Gamalte Elgedawy Radwa Gamal Osama Zaki Ashraf Khalil Manar Obada |
| author_facet | Nadia Salama Gamalte Elgedawy Radwa Gamal Osama Zaki Ashraf Khalil Manar Obada |
| author_sort | Nadia Salama |
| collection | DOAJ |
| description | Abstract Tetrahydrobiopterin deficiency in newborns with atypical hyperphenylalaninemia requires rapid and accurate diagnosis and the ability to distinguish it from the classical type to prevent early irreversible neurological damage. The study aimed to evaluate neopterin and biopterin (products of tetrahydrobiopterin recycling pathway) and amino acid profiles (used in supplementation therapy) in patients with hyperphenylalaninemia after optimizing ultra-performance liquid chromatography coupled with tandem mass spectrometry to simultaneously measure neopterin, biopterin, and amino acids in dried blood spots. The study enrolled preselected infants with classic (n = 46), atypical (n = 14) hyperphenylalaninemia, and a control group (n = 50). Result Tandem mass spectrometry detected neo/biopterin in the blood with a sensitivity and specificity of 100%. The mean neo/biopterin levels were significantly lower in the atypical cases (4 ± 1 and 3 ± 1 nmol/L) than the classic (49 ± 13 and 50 ± 12 nmol/L) and control (15.2 and 15.3 nmol/L) groups and correlated with phenylalanine and phenylalanine to tyrosine ratio (all P < 0.05). The study compared classic and atypical hyperphenylalaninemia cases with the control group. Both classic and atypical cases exhibited decreased levels of arginine, valine, and leucine compared to controls. Classic cases showed increased levels of citrulline, ornithine, and methionine, while atypical cases showed increased citrulline levels only. Comparing atypical versus classic cases, atypical cases exhibited decreased levels of citrulline, ornithine, methionine, arginine, leucine, and valine (all P < 0.05). Correlation analysis revealed negative associations between ornithine and biopterin and between arginine and neopterin in classic PKU cases. These findings highlight distinct metabolic differences between classic and atypical PKU. Conclusion The optimized method detected neo/biopterin in the blood with accuracy and precision. The characteristic pattern of neo/biopterin in the blood makes it possible to differentiate between classic and atypical hyperphenylalaninemia with a sensitivity and specificity of 100%. The amino acid profile could add value when treatment with large neutral amino acids is considered. |
| first_indexed | 2024-03-08T12:40:13Z |
| format | Article |
| id | doaj.art-3cf44746b57e452ca673395eedb7f82b |
| institution | Directory Open Access Journal |
| issn | 2090-6226 |
| language | English |
| last_indexed | 2024-03-08T12:40:13Z |
| publishDate | 2024-01-01 |
| publisher | SpringerOpen |
| record_format | Article |
| series | Egyptian Liver Journal |
| spelling | doaj.art-3cf44746b57e452ca673395eedb7f82b2024-01-21T12:11:06ZengSpringerOpenEgyptian Liver Journal2090-62262024-01-0114111010.1186/s43066-024-00312-zThe value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemiaNadia Salama0Gamalte Elgedawy1Radwa Gamal2Osama Zaki3Ashraf Khalil4Manar Obada5Department of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoffia UniversityDepartment of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoffia UniversityDepartment of Human Genetics, Ain Shams UniversityDepartment of Human Genetics, Ain Shams UniversityDepartment of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoffia UniversityDepartment of Clinical Biochemistry and Molecular Diagnostics, National Liver Institute, Menoffia UniversityAbstract Tetrahydrobiopterin deficiency in newborns with atypical hyperphenylalaninemia requires rapid and accurate diagnosis and the ability to distinguish it from the classical type to prevent early irreversible neurological damage. The study aimed to evaluate neopterin and biopterin (products of tetrahydrobiopterin recycling pathway) and amino acid profiles (used in supplementation therapy) in patients with hyperphenylalaninemia after optimizing ultra-performance liquid chromatography coupled with tandem mass spectrometry to simultaneously measure neopterin, biopterin, and amino acids in dried blood spots. The study enrolled preselected infants with classic (n = 46), atypical (n = 14) hyperphenylalaninemia, and a control group (n = 50). Result Tandem mass spectrometry detected neo/biopterin in the blood with a sensitivity and specificity of 100%. The mean neo/biopterin levels were significantly lower in the atypical cases (4 ± 1 and 3 ± 1 nmol/L) than the classic (49 ± 13 and 50 ± 12 nmol/L) and control (15.2 and 15.3 nmol/L) groups and correlated with phenylalanine and phenylalanine to tyrosine ratio (all P < 0.05). The study compared classic and atypical hyperphenylalaninemia cases with the control group. Both classic and atypical cases exhibited decreased levels of arginine, valine, and leucine compared to controls. Classic cases showed increased levels of citrulline, ornithine, and methionine, while atypical cases showed increased citrulline levels only. Comparing atypical versus classic cases, atypical cases exhibited decreased levels of citrulline, ornithine, methionine, arginine, leucine, and valine (all P < 0.05). Correlation analysis revealed negative associations between ornithine and biopterin and between arginine and neopterin in classic PKU cases. These findings highlight distinct metabolic differences between classic and atypical PKU. Conclusion The optimized method detected neo/biopterin in the blood with accuracy and precision. The characteristic pattern of neo/biopterin in the blood makes it possible to differentiate between classic and atypical hyperphenylalaninemia with a sensitivity and specificity of 100%. The amino acid profile could add value when treatment with large neutral amino acids is considered.https://doi.org/10.1186/s43066-024-00312-zTandem mass spectrometryNeopterinBiopterinAtypical hyperphenylalaninaemia |
| spellingShingle | Nadia Salama Gamalte Elgedawy Radwa Gamal Osama Zaki Ashraf Khalil Manar Obada The value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia Egyptian Liver Journal Tandem mass spectrometry Neopterin Biopterin Atypical hyperphenylalaninaemia |
| title | The value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia |
| title_full | The value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia |
| title_fullStr | The value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia |
| title_full_unstemmed | The value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia |
| title_short | The value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia |
| title_sort | value of simultaneous determination of blood large neutral amino acids and tetrahydrobiopterin metabolites in the diagnosis of atypical hyperphenylalaninemia |
| topic | Tandem mass spectrometry Neopterin Biopterin Atypical hyperphenylalaninaemia |
| url | https://doi.org/10.1186/s43066-024-00312-z |
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