Response to Therapy in Carnitine/Acylcarnitine Translocase (CACT) Deficiency Due to a Novel Missense Mutation

Vito Iacobazzi, Marzia Pasquali, Rani Singh, Dietrich Matern, Piero Rinaldo, Cristina Amat Di San Filippo, Ferdinando Palmieri, Nicola Longo

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Deficiency of carnitine/acylcarnitine translocase (CACT) is an autosomal recessive disorder of the carnitine cycle resulting in the inability to transfer fatty acids across the inner mitochondrial membrane. Only a limited number of affected patients have been reported and the effect of therapy on this condition is still not well defined. Here, we report a new patient with this disorder and follow the response to therapy. Our patient was the product of a consanguineous marriage. He presented shortly after birth with cardiac myopathy and arrhythmia coupled with severe non-ketotic hypoglycemia. Initial metabolic studies indicated severe non-ketotic C6-C10 dicarboxylic aciduria, plasma carnitine deficiency, and a characteristic elevation of plasma C:16:0, C18:1, and C18:2 acylcarnitine species. Enzyme assay confirmed deficiency of CACT activity. Molecular studies indicated that this child was homozygous, and both parents heterozygous, for a single bp change converting glutamine 238 to arginine (Q238R). Therapy with a formula providing most of the fat via medium chain triglycerides (MCT) and carnitine supplementation reduced the concentration of long-chain acylcarnitines and reversed cardiac symptoms and the hypoglycemia. These results suggest that carnitine and MCT may be effective in treating this defect of long-chain fatty acid oxidation.

Original languageEnglish (US)
Pages (from-to)150-155
Number of pages6
JournalAmerican Journal of Medical Genetics
Volume126 A
Issue number2
StatePublished - Apr 15 2004

Fingerprint

Carnitine
Missense Mutation
Hypoglycemia
Triglycerides
Fatty Acids
Enzyme Assays
Mitochondrial Membranes
Muscular Diseases
Therapeutics
Marriage
Glutamine
Arginine
Cardiac Arrhythmias
Parents
Fats
Parturition
Carnitine-Acylcarnitine Translocase Deficiency
acylcarnitine

Keywords

  • Cardiac arrhythmia
  • Cardiomyopathy
  • Carnitine deficiency
  • Fatty acid oxidation
  • Hypoglycemia
  • SLC25A20

ASJC Scopus subject areas

  • Genetics(clinical)

Cite this

Iacobazzi, V., Pasquali, M., Singh, R., Matern, D., Rinaldo, P., Di San Filippo, C. A., ... Longo, N. (2004). Response to Therapy in Carnitine/Acylcarnitine Translocase (CACT) Deficiency Due to a Novel Missense Mutation. American Journal of Medical Genetics, 126 A(2), 150-155.

Response to Therapy in Carnitine/Acylcarnitine Translocase (CACT) Deficiency Due to a Novel Missense Mutation. / Iacobazzi, Vito; Pasquali, Marzia; Singh, Rani; Matern, Dietrich; Rinaldo, Piero; Di San Filippo, Cristina Amat; Palmieri, Ferdinando; Longo, Nicola.

In: American Journal of Medical Genetics, Vol. 126 A, No. 2, 15.04.2004, p. 150-155.

Research output: Contribution to journalArticle

Iacobazzi, V, Pasquali, M, Singh, R, Matern, D, Rinaldo, P, Di San Filippo, CA, Palmieri, F & Longo, N 2004, 'Response to Therapy in Carnitine/Acylcarnitine Translocase (CACT) Deficiency Due to a Novel Missense Mutation', American Journal of Medical Genetics, vol. 126 A, no. 2, pp. 150-155.
Iacobazzi V, Pasquali M, Singh R, Matern D, Rinaldo P, Di San Filippo CA et al. Response to Therapy in Carnitine/Acylcarnitine Translocase (CACT) Deficiency Due to a Novel Missense Mutation. American Journal of Medical Genetics. 2004 Apr 15;126 A(2):150-155.
Iacobazzi, Vito ; Pasquali, Marzia ; Singh, Rani ; Matern, Dietrich ; Rinaldo, Piero ; Di San Filippo, Cristina Amat ; Palmieri, Ferdinando ; Longo, Nicola. / Response to Therapy in Carnitine/Acylcarnitine Translocase (CACT) Deficiency Due to a Novel Missense Mutation. In: American Journal of Medical Genetics. 2004 ; Vol. 126 A, No. 2. pp. 150-155.
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