Carnitine Acylcarnitine Translocase Deficiency: 16 Cases with Survival in 10

Abstract

Background: Carnitine-acylcarnitine translocase deficiency (CACTD) is a rare disorder of fatty acid oxidation. Patients typically present <48 h with cardiomyopathy or arrhythmias, hypoketotic hy-poglycemia, hyperammonemia, hepatomegaly, raised liver transam-inases and elevated creatine phosphokinase (CPK). Sudden unexpected death in infancy is common and outcomes remain poor despite treatment. Method: Retrospective review of 16 cases from Australia, Canada, England, France, and New Zealand, with diagnosis confirmed by enzyme activity and/or molecular analysis. Results: 11/16 presented at 10-48 h of age; 2/16, with affected siblings, were treated from birth, and one pre-symptomatically following newborn screening (NBS). Two presented at 9 and 14 days. Hypoglycemia was noted in 12/13 presenting clinically; hyperammonemia in 10/13. Transaminases were modestly elevated in 10/13 and CPK ranged from normal to >25,000 U/l. Neonatal cardiomyopathy was demonstrated in two cases with reduced contractility in 3/16, and arrhythmias in 5/16. Six cases had acute renal impairment, three had tubulopathy. Free carnitine was low in 9/13. C16-carnitine was elevated in all (3.95-21.1 umol/l). 3/16 patients died in the neonatal period, and 5/16 by age 4. 10/16 patients survived to aged 1-10 years. Neurocognitive outcome was normal in 6/16, including 3/16 treated presymptomatically. Discussion: CACTD causes acute metabolic decompensation associated with hyperammonemia, hypoglycemia, cardiac dysfunction and encephalopathy. Gastrointestinal disturbance is common. Less reported renal manifestations include tubul-opathy and renal failure. Hyperammonemia is sensitive to high rates of glucose administration but can be difficult to manage long term. NBS may expedite the diagnosis but urgent intervention is required.L6298895102019-11-25 <br />