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 language | English (US) |
|---|---|
| Pages (from-to) | 150-155 |
| Number of pages | 6 |
| Journal | American Journal of Medical Genetics |
| Volume | 126 A |
| Issue number | 2 |
| State | Published - Apr 15 2004 |
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Keywords
- Cardiac arrhythmia
- Cardiomyopathy
- Carnitine deficiency
- Fatty acid oxidation
- Hypoglycemia
- SLC25A20
ASJC Scopus subject areas
- Genetics(clinical)
Cite this
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 journal › Article
}
TY - JOUR
T1 - Response to Therapy in Carnitine/Acylcarnitine Translocase (CACT) Deficiency Due to a Novel Missense Mutation
AU - Iacobazzi, Vito
AU - Pasquali, Marzia
AU - Singh, Rani
AU - Matern, Dietrich
AU - Rinaldo, Piero
AU - Di San Filippo, Cristina Amat
AU - Palmieri, Ferdinando
AU - Longo, Nicola
PY - 2004/4/15
Y1 - 2004/4/15
N2 - 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.
AB - 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.
KW - Cardiac arrhythmia
KW - Cardiomyopathy
KW - Carnitine deficiency
KW - Fatty acid oxidation
KW - Hypoglycemia
KW - SLC25A20
UR - http://www.scopus.com/inward/record.url?scp=1842586064&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1842586064&partnerID=8YFLogxK
M3 - Article
C2 - 15057979
AN - SCOPUS:1842586064
VL - 126 A
SP - 150
EP - 155
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
SN - 0148-7299
IS - 2
ER -