Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories
Abstract Background The ‘classic’ organic acidaemias (OAs) (propionic, methylmalonic and isovaleric) typically present in neonates or infants as acute metabolic decompensation with encephalopathy. This is frequently accompanied by severe hyperammonaemia and constitutes a metabolic emergency, as incr...
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| Format: | Article |
| Language: | English |
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BMC
2018-12-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | http://link.springer.com/article/10.1186/s13023-018-0963-7 |
| _version_ | 1818490834853560320 |
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| author | Johannes Häberle Anupam Chakrapani Nicholas Ah Mew Nicola Longo |
| author_facet | Johannes Häberle Anupam Chakrapani Nicholas Ah Mew Nicola Longo |
| author_sort | Johannes Häberle |
| collection | DOAJ |
| description | Abstract Background The ‘classic’ organic acidaemias (OAs) (propionic, methylmalonic and isovaleric) typically present in neonates or infants as acute metabolic decompensation with encephalopathy. This is frequently accompanied by severe hyperammonaemia and constitutes a metabolic emergency, as increased ammonia levels and accumulating toxic metabolites are associated with life-threatening neurological complications. Repeated and frequent episodes of hyperammonaemia (alongside metabolic decompensations) can result in impaired growth and intellectual disability, the severity of which increase with longer duration of hyperammonaemia. Due to the urgency required, diagnostic evaluation and initial management of patients with suspected OAs should proceed simultaneously. Paediatricians, who do not have specialist knowledge of metabolic disorders, have the challenging task of facilitating a timely diagnosis and treatment. This article outlines how the underlying pathophysiology and biochemistry of the organic acidaemias are closely linked to their clinical presentation and management, and provides practical advice for decision-making during early, acute hyperammonaemia and metabolic decompensation in neonates and infants with organic acidaemias. Clinical management The acute management of hyperammonaemia in organic acidaemias requires administration of intravenous calories as glucose and lipids to promote anabolism, carnitine to promote urinary excretion of urinary organic acid esters, and correction of metabolic acidosis with the substitution of bicarbonate for chloride in intravenous fluids. It may also include the administration of ammonia scavengers such as sodium benzoate or sodium phenylbutyrate. Treatment with N-carbamyl-L-glutamate can rapidly normalise ammonia levels by stimulating the first step of the urea cycle. Conclusions Our understanding of optimal treatment strategies for organic acidaemias is still evolving. Timely diagnosis is essential and best achieved by the early identification of hyperammonaemia and metabolic acidosis. Correcting metabolic imbalance and hyperammonaemia are critical to prevent brain damage in affected patients. |
| first_indexed | 2024-12-10T17:22:47Z |
| format | Article |
| id | doaj.art-92793fe7f92442e2abeeadb29be96ef6 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-10T17:22:47Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-92793fe7f92442e2abeeadb29be96ef62022-12-22T01:39:56ZengBMCOrphanet Journal of Rare Diseases1750-11722018-12-0113111010.1186/s13023-018-0963-7Hyperammonaemia in classic organic acidaemias: a review of the literature and two case historiesJohannes Häberle0Anupam Chakrapani1Nicholas Ah Mew2Nicola Longo3Division of Metabolism and Children’s Research Centre, University Children’s Hospital ZurichDepartment of Clinical Inherited Metabolic Disorders, Great Ormond Street Hospital for Children NHS Foundation TrustChildren’s National Rare Disease Institute, Children’s National Health SystemDepartment of Pediatrics, Division of Medical Genetics, University of Utah School of MedicineAbstract Background The ‘classic’ organic acidaemias (OAs) (propionic, methylmalonic and isovaleric) typically present in neonates or infants as acute metabolic decompensation with encephalopathy. This is frequently accompanied by severe hyperammonaemia and constitutes a metabolic emergency, as increased ammonia levels and accumulating toxic metabolites are associated with life-threatening neurological complications. Repeated and frequent episodes of hyperammonaemia (alongside metabolic decompensations) can result in impaired growth and intellectual disability, the severity of which increase with longer duration of hyperammonaemia. Due to the urgency required, diagnostic evaluation and initial management of patients with suspected OAs should proceed simultaneously. Paediatricians, who do not have specialist knowledge of metabolic disorders, have the challenging task of facilitating a timely diagnosis and treatment. This article outlines how the underlying pathophysiology and biochemistry of the organic acidaemias are closely linked to their clinical presentation and management, and provides practical advice for decision-making during early, acute hyperammonaemia and metabolic decompensation in neonates and infants with organic acidaemias. Clinical management The acute management of hyperammonaemia in organic acidaemias requires administration of intravenous calories as glucose and lipids to promote anabolism, carnitine to promote urinary excretion of urinary organic acid esters, and correction of metabolic acidosis with the substitution of bicarbonate for chloride in intravenous fluids. It may also include the administration of ammonia scavengers such as sodium benzoate or sodium phenylbutyrate. Treatment with N-carbamyl-L-glutamate can rapidly normalise ammonia levels by stimulating the first step of the urea cycle. Conclusions Our understanding of optimal treatment strategies for organic acidaemias is still evolving. Timely diagnosis is essential and best achieved by the early identification of hyperammonaemia and metabolic acidosis. Correcting metabolic imbalance and hyperammonaemia are critical to prevent brain damage in affected patients.http://link.springer.com/article/10.1186/s13023-018-0963-7Metabolic acidosisHyperammonaemiaOrganic acidaemiasMetabolic decompensationBiochemical pathogenesis |
| spellingShingle | Johannes Häberle Anupam Chakrapani Nicholas Ah Mew Nicola Longo Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories Orphanet Journal of Rare Diseases Metabolic acidosis Hyperammonaemia Organic acidaemias Metabolic decompensation Biochemical pathogenesis |
| title | Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories |
| title_full | Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories |
| title_fullStr | Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories |
| title_full_unstemmed | Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories |
| title_short | Hyperammonaemia in classic organic acidaemias: a review of the literature and two case histories |
| title_sort | hyperammonaemia in classic organic acidaemias a review of the literature and two case histories |
| topic | Metabolic acidosis Hyperammonaemia Organic acidaemias Metabolic decompensation Biochemical pathogenesis |
| url | http://link.springer.com/article/10.1186/s13023-018-0963-7 |
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