N‐acetylglutamate synthase deficiency with associated 3‐methylglutaconic aciduria: A case report
Abstract N‐acetylglutamate synthase (NAGS) deficiency is a rare autosomal recessive disorder, which results in the inability to activate the key urea cycle enzyme, carbamoylphosphate synthetase 1 (CPS1). Patients often suffer life‐threatening episodes of hyperammonaemia, both in the neonatal period...
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| Format: | Article |
| Language: | English |
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Wiley
2022-09-01
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| Series: | JIMD Reports |
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| Online Access: | https://doi.org/10.1002/jmd2.12318 |
| _version_ | 1811274052009984000 |
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| author | Arthavan Selvanathan Kalliope Demetriou Matthew Lynch Michelle Lipke Carolyn Bursle Aoife Elliott Anita Inwood Leanne Foyn Brett McWhinney David Coman Jim McGill |
| author_facet | Arthavan Selvanathan Kalliope Demetriou Matthew Lynch Michelle Lipke Carolyn Bursle Aoife Elliott Anita Inwood Leanne Foyn Brett McWhinney David Coman Jim McGill |
| author_sort | Arthavan Selvanathan |
| collection | DOAJ |
| description | Abstract N‐acetylglutamate synthase (NAGS) deficiency is a rare autosomal recessive disorder, which results in the inability to activate the key urea cycle enzyme, carbamoylphosphate synthetase 1 (CPS1). Patients often suffer life‐threatening episodes of hyperammonaemia, both in the neonatal period and also at subsequent times of catabolic stress. Because NAGS generates the cofactor for CPS1, these two disorders are difficult to distinguish biochemically. However, there have now been numerous case reports of 3‐methylglutaconic aciduria (3‐MGA), a marker seen in mitochondrial disorders, occurring in CPS1 deficiency. Previously, this had not been reported in NAGS deficiency. We report a four‐day‐old neonate who was noted to have 3‐MGA at the time of significant hyperammonaemia and lactic acidosis. Low plasma citrulline and borderline orotic aciduria were additional findings that suggested a proximal urea cycle disorder. Subsequent molecular testing identified bi‐allelic pathogenic variants in NAGS. The 3‐MGA was present at the time of persistent lactic acidosis, but improved with normalization of serum lactate, suggesting that it may reflect secondary mitochondrial dysfunction. NAGS deficiency should therefore also be considered in patients with hyperammonaemia and 3‐MGA. Studies in larger numbers of patients are required to determine whether it could be a biomarker for severe decompensations. |
| first_indexed | 2024-04-12T23:12:01Z |
| format | Article |
| id | doaj.art-baa9a26fcbdc464fb979306bb62699ec |
| institution | Directory Open Access Journal |
| issn | 2192-8312 |
| language | English |
| last_indexed | 2024-04-12T23:12:01Z |
| publishDate | 2022-09-01 |
| publisher | Wiley |
| record_format | Article |
| series | JIMD Reports |
| spelling | doaj.art-baa9a26fcbdc464fb979306bb62699ec2022-12-22T03:12:47ZengWileyJIMD Reports2192-83122022-09-0163542042410.1002/jmd2.12318N‐acetylglutamate synthase deficiency with associated 3‐methylglutaconic aciduria: A case reportArthavan Selvanathan0Kalliope Demetriou1Matthew Lynch2Michelle Lipke3Carolyn Bursle4Aoife Elliott5Anita Inwood6Leanne Foyn7Brett McWhinney8David Coman9Jim McGill10Queensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane AustraliaQueensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane AustraliaQueensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane AustraliaQueensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane AustraliaQueensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane AustraliaQueensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane AustraliaQueensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane AustraliaChemical Pathology, Central Laboratory Pathology Queensland Herston AustraliaChemical Pathology, Central Laboratory Pathology Queensland Herston AustraliaQueensland Lifespan Metabolic Medicine Service Queensland Children's Hospital Brisbane AustraliaChemical Pathology, Central Laboratory Pathology Queensland Herston AustraliaAbstract N‐acetylglutamate synthase (NAGS) deficiency is a rare autosomal recessive disorder, which results in the inability to activate the key urea cycle enzyme, carbamoylphosphate synthetase 1 (CPS1). Patients often suffer life‐threatening episodes of hyperammonaemia, both in the neonatal period and also at subsequent times of catabolic stress. Because NAGS generates the cofactor for CPS1, these two disorders are difficult to distinguish biochemically. However, there have now been numerous case reports of 3‐methylglutaconic aciduria (3‐MGA), a marker seen in mitochondrial disorders, occurring in CPS1 deficiency. Previously, this had not been reported in NAGS deficiency. We report a four‐day‐old neonate who was noted to have 3‐MGA at the time of significant hyperammonaemia and lactic acidosis. Low plasma citrulline and borderline orotic aciduria were additional findings that suggested a proximal urea cycle disorder. Subsequent molecular testing identified bi‐allelic pathogenic variants in NAGS. The 3‐MGA was present at the time of persistent lactic acidosis, but improved with normalization of serum lactate, suggesting that it may reflect secondary mitochondrial dysfunction. NAGS deficiency should therefore also be considered in patients with hyperammonaemia and 3‐MGA. Studies in larger numbers of patients are required to determine whether it could be a biomarker for severe decompensations.https://doi.org/10.1002/jmd2.123183‐methylglutaconic aciduriamitochondrial dysfunctionN‐acetylglutamate synthase deficiencyUrea cycle disorder |
| spellingShingle | Arthavan Selvanathan Kalliope Demetriou Matthew Lynch Michelle Lipke Carolyn Bursle Aoife Elliott Anita Inwood Leanne Foyn Brett McWhinney David Coman Jim McGill N‐acetylglutamate synthase deficiency with associated 3‐methylglutaconic aciduria: A case report JIMD Reports 3‐methylglutaconic aciduria mitochondrial dysfunction N‐acetylglutamate synthase deficiency Urea cycle disorder |
| title | N‐acetylglutamate synthase deficiency with associated 3‐methylglutaconic aciduria: A case report |
| title_full | N‐acetylglutamate synthase deficiency with associated 3‐methylglutaconic aciduria: A case report |
| title_fullStr | N‐acetylglutamate synthase deficiency with associated 3‐methylglutaconic aciduria: A case report |
| title_full_unstemmed | N‐acetylglutamate synthase deficiency with associated 3‐methylglutaconic aciduria: A case report |
| title_short | N‐acetylglutamate synthase deficiency with associated 3‐methylglutaconic aciduria: A case report |
| title_sort | n acetylglutamate synthase deficiency with associated 3 methylglutaconic aciduria a case report |
| topic | 3‐methylglutaconic aciduria mitochondrial dysfunction N‐acetylglutamate synthase deficiency Urea cycle disorder |
| url | https://doi.org/10.1002/jmd2.12318 |
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