dc.contributor.author | Ryder, B | |
dc.contributor.author | Inbar-Feigenberg, M | |
dc.contributor.author | Glamuzina, E | |
dc.contributor.author | Halligan, R | |
dc.contributor.author | Vara, R | |
dc.contributor.author | Elliot, A | |
dc.contributor.author | Coman, D | |
dc.contributor.author | Minto, T | |
dc.contributor.author | Lewis, K | |
dc.contributor.author | Schiff, M | |
dc.contributor.author | Vijay, S | |
dc.contributor.author | Akroyd, R | |
dc.contributor.author | Thompson, S | |
dc.contributor.author | MacDonald, A | |
dc.contributor.author | et al. | |
dc.date.accessioned | 2021-03-09T23:58:30Z | |
dc.date.available | 2021-03-09T23:58:30Z | |
dc.date.issued | 2021 | |
dc.identifier.issn | 0141-8955 | |
dc.identifier.doi | 10.1002/jimd.12371 | |
dc.identifier.uri | http://hdl.handle.net/10072/403020 | |
dc.description.abstract | BACKGROUND: Carnitine acyl-carnitine translocase deficiency (CACTD) is a rare autosomal recessive disorder of mitochondrial long-chain fatty-acid transport. Most patients present in the first two days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. METHOD: Multi-centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. RESULTS: Twenty-three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, 6 of these homozygous c.82G>T, had later onset manifestations and long-term survival without chronic hyperammonemia. Of the sixteen classical cases, fifteen had cardiac involvement at presentation comprising cardiac arrhythmias (9/15), cardiac arrest (7/15) and cardiac hypertrophy (9/15). Where recorded, ammonia levels were elevated in all but one severe case (13/14 measured) and 14/16 had hypoglycaemia. Nine classical patients survived longer-term - most with feeding difficulties and cognitive delay. Hyperammonaemia appears refractory to ammonia scavenger treatment and carglumic acid, but responds well to high glucose delivery during acute metabolic crises. High-energy intake seems necessary to prevent decompensation. Anaplerosis utilizing therapeutic D,L-3-hydroxybutyrate, Triheptanoin and increased protein intake, appeared to improve chronic hyperammonemia and metabolic stability where trialled in individual cases. CONCLUSION: CACTD is a rare disorder of fatty acid oxidation with a preponderance to severe cardiac dysfunction. Long-term survival is possible in classical early-onset cases with long-chain fat restriction, judicious use of glucose infusions, and medium chain triglyceride supplementation. Adjunctive therapies supporting anaplerosis may improve longer-term outcomes. This article is protected by copyright. All rights reserved. | |
dc.description.peerreviewed | Yes | |
dc.language | eng | |
dc.publisher | Wiley | |
dc.relation.ispartofjournal | Journal of Inherited Metabolic Disease (JIMD) | |
dc.subject.fieldofresearch | Clinical sciences | |
dc.subject.fieldofresearchcode | 3202 | |
dc.subject.keywords | Carnitine acyl-carnitine translocase deficiency | |
dc.subject.keywords | Triheptanoin | |
dc.subject.keywords | anaplerosis | |
dc.subject.keywords | carnitine shuttle | |
dc.subject.keywords | hyperammonaemia | |
dc.title | New insights into carnitine-acylcarnitine translocase deficiency from twenty-three cases: management challenges and potential therapeutic approaches | |
dc.type | Journal article | |
dc.type.description | C1 - Articles | |
dcterms.bibliographicCitation | Ryder, B; Inbar-Feigenberg, M; Glamuzina, E; Halligan, R; Vara, R; Elliot, A; Coman, D; Minto, T; Lewis, K; Schiff, M; Vijay, S; Akroyd, R; Thompson, S; MacDonald, A; et al., New insights into carnitine-acylcarnitine translocase deficiency from twenty-three cases: management challenges and potential therapeutic approaches, Journal of Inherited Metabolic Disease (JIMD), 2021 | |
dcterms.dateAccepted | 2021-02-23 | |
dc.date.updated | 2021-03-09T23:09:28Z | |
dc.description.version | Accepted Manuscript (AM) | |
gro.description.notepublic | This publication has been entered in Griffith Research Online as an advanced online version. | |
gro.rights.copyright | © 2021 Society for the Study of Addiction. This is the peer reviewed version of the following article: New insights into carnitine-acylcarnitine translocase deficiency from twenty-three cases: management challenges and potential therapeutic approaches, Journal of Inherited Metabolic Disease (JIMD), 2021, which has been published in final form at https://doi.org/10.1002/jimd.12371. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving (http://olabout.wiley.com/WileyCDA/Section/id-828039.html) | |
gro.hasfulltext | Full Text | |
gro.griffith.author | Coman, Dave J. | |