New insights into carnitine‐acylcarnitine translocase deficiency from 23 cases: Management challenges and potential therapeutic approaches. Issue 4 (29th March 2021)

• Record Type: Journal Article
• Authors: Ryder, Bryony; Inbar‐Feigenberg, Michal; Glamuzina, Emma; Halligan, Rebecca; Vara, Roshni; Elliot, Aoife; Coman, David; Minto, Tahlee; Lewis, Katherine; Schiff, Manuel; Vijay, Suresh; Akroyd, Rhonda; Thompson, Sue; MacDonald, Anita; Woodward, Abigail J. M.; Gribben, Joanne. E. L.; Grunewald, Stephanie; Belaramani, Kiran; Hall, Madeleine; van der Haak, Natalie; Devanapalli, Beena; Tolun, Adviye Ayper; Wilson, Callum; Bhattacharya, Kaustuv
• Is Part Of: Journal of inherited metabolic disease. Volume 44:Issue 4(2021)
• Page Start: 903
• Page End: 915
• Publication Date: 2021-03-29
• Subjects: anaplerosis -- carnitine acyl‐carnitine translocase deficiency -- carnitine shuttle -- hyperammonaemia -- ketones -- Triheptanoin; Metabolism, Inborn errors of -- Periodicals; Metabolism -- Disorders -- Periodicals; 616.39042
• DOI: 10.1002/jimd.12371
• Languages: English
• ISSNs: 0141-8955

Abstract

Abstract: 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 2 days of life, with hypoketotic hypoglycaemia, hyperammonaemia, cardiomyopathy or arrhythmia, hepatomegaly and elevated liver enzymes. Multi‐centre international retrospective chart review of clinical presentation, biochemistry, treatment modalities including diet, subsequent complications, and mode of death of all patients. Twenty‐three patients from nine tertiary metabolic units were identified. Seven attenuated patients of Pakistani heritage, six of these homozygous c.82G>T, had later onset manifestations and long‐term survival without chronic hyperammonemia. Of the 16 classical cases, 15 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 utilising therapeutic d, l ‐3‐hydroxybutyrate, Triheptanoin and increased protein intake, appeared to improve chronic hyperammonemia and metabolic stability where trialled in individual cases. 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.