Abstract
Background: Carnitine-acylcarnitine translocase (CACT) deficiency is a rare autosomal recessive disease in the mitochondrial transport of long-chain fatty acids. Despite early diagnosis and treatment, the disease still has a high mortality rate.
Methods: Clinical symptoms, long-term follow-up, and biochemical and molecular results of four cases are described and compared with the reviewed literature data of 55 cases.
Results: Two cases with neonatal onset, carrying in homozygosity the novel variant sequences p.Gly20Asp (c.59G>A) and p.Arg179Gly (c.536A>G), died during an intercurrent infectious process in the first year of life despite adequate dietetic treatment (frequent feeding, high-carbohydrate/low-fat diet, MCT, carnitine). The other two cases, one with infantile onset and the other diagnosed in the newborn period after a previous affected sibling, show excellent development at 4 and 16 years of age under treatment. The review shows that the most frequent presenting symptoms of CACT deficiency are hypoketotic hypoglycemia, hyperammonemia, hepatomegaly, cardiomyopathy and/or arrhythmia, and respiratory distress. The onset of symptoms is predominantly neonatal in 82% and infantile in 18%. The mortality rate is high (65%), most in the first year of life due to myocardiopathy or sudden death. Outcomes seem to correlate better with the absence of cardiac disease and with a higher long-chain fatty acid oxidation rate in cultured fibroblasts than with residual enzyme activity.
Conclusion: Diagnosis before the occurrence of clinical symptoms by tandem MS–MS and very early therapeutic intervention together with good dietary compliance could lead to a better prognosis, especially in milder clinical cases.
Competing interests: None declared
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Acknowledgments
The authors would like to thank the families for giving their consent. We are grateful to Dr. Nerea Gorria from Hospital General Yagüe in Burgos for supplying the first clinical data from case 3. We gratefully acknowledge the funding by Mitolab (S2010/BMD-2402) DGUI Comunidad de Madrid.
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Communicated by: Gregory Enns
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Take-Home Message
Long-term clinical outcome in carnitine-acylcarnitine translocase deficiency seems to be better in those cases with a very early therapeutic intervention and a good dietary compliance with diet.
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I Vitoria, E Martín-Hernández, L Peña-Quintana, M Bueno, P Quijada-Fraile, J Dalmau, S Molina-Marrero, B Pérez, and B Merinero declare that they have no conflict of interest.
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All procedures followed were in accordance with the ethical standards of the responsible committee on human experimentation (institutional and national) and with the Helsinki Declaration of 1975, as revised in 2000. Informed consent was obtained from all patients for being included in the study.
Details of the Contributions of Individual Authors
IV: clinical data of case 1, conception and design, drafting, and coordination of the manuscript
EM-H: clinical data of case 3, analysis of the data, and critical reading of the manuscript
LP-Q: clinical data of case 2, analysis of the data, and critical reading of the manuscript
MB: clinical care of case 4 and critical reading of the manuscript
PQF: critical reading of the manuscript
JD: clinical data of case 1 and critical reading of the manuscript
SM-M: clinical data of case 2 and critical reading of the manuscript
BP: molecular genetic analysis and interpretation of cases 1, 2, and 3
BM: biochemical diagnosis and interpretation of cases 1, 2, and 3, conception and design, and drafting of the manuscript
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Vitoria, I. et al. (2014). Carnitine-Acylcarnitine Translocase Deficiency: Experience with Four Cases in Spain and Review of the Literature. In: Zschocke, J., Baumgartner, M., Morava, E., Patterson, M., Rahman, S., Peters, V. (eds) JIMD Reports, Volume 20. JIMD Reports, vol 20. Springer, Berlin, Heidelberg. https://doi.org/10.1007/8904_2014_382
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