Carnitine-acylcarnitine translocase (also known as CACT) deficiency is a very rare inherited fatty acid oxidation disorder. To date, less than 60 cases have been reported worldwide. This disorder most often follows an autosomal recessive inheritance pattern and usually presents in the neonatal period with severe hypoketotic hypoglycemia, hyperammonemia, cardiomyopathy and/or arrhythmia, hepatic dysfunction, skeletal muscle weakness, and encephalopathy. The prognosis of CACT is poor; many infants with this deficiency do not survive the newborn period.
Mutations in the SLC25A20 gene have been identified in patients with CACT deficiency. SLC25A20 encodes a protein called carnitine-acylcarnitine translocase (CACT), which transports long-chain fatty acid carnitine esters into the mitochondrial matrix. CACT enzyme is an essential component for fatty acid beta-oxidation and energy production in the mitochondria. Deficiency of this transport protein results in impaired long-chain fatty acid oxidation and causes the accumulation of long-chain acylcarnitines outside the mitochondria and in plasma.
Galron et al. (2004) reported a male patient with CACTD from a consanguineous Bedouin background. The infant developed clinical signs of an acute metabolic crisis with severe hypoglycaemia and hyperammonaemia on his second day of life. Biochemical results and molecular analysis confirmed the presence of the condition as the patient harbored a novel homozygous missense mutation 793A>G, substituting glutamine by arginine (Q238R) in exon 7 of the CACT gene. The patient did not survive beyond his 6th month despite intensive medical attention.
Al Aqeel et al., (2003) reported a 5 year-old month Saudi girl affected with severe carnitine-acylcarnitine translocase deficiency. She was born to first cousin parents, with a history of three neonatal deaths. At the second day of life she presented with nystagmus and hyperammonemia. Acyl carnitine analysis showed highly elevated C16 and C17, with normal level of free carnitine. She had a thickened interventricular septum. She was hospitalized at the age of 4 months due to respiratory distress and a high ammonia level, pulmonary infiltrates and became oxygen dependent, requiring ventilation. She died at the age of 7 months as a result of cardiac arrhythmia. The causative missense mutation resulted in (Q238R) in carnitine-acylcarnitine translocase.
Iacobazzi et al., (2004) described an Arab boy who was born to consanguineous parents with carnitine/acylcarnitine translocase deficiency. He developed at hypothermia, hypoxemia, low blood pressure, and hypoglycemia at 18-hr of life. Family history revealed that another child, a female, had died at 3-days of age with an illness similar to her brother. At 2-years of age, he was on low-fat diet rich in MCT (medium-chain triglycerides) oil, frequent feeds with continuous feeds at night, and carnitine therapy. A homozygous mutation in the SLC25A20 gene was identified in the child. Both parents were heterozygous for the same mutation.
Moammar et al. (2010) reviewed all patients diagnosed with inborn errors of metabolism (IEM) from 1983 to 2008 at Saudi Aramco medical facilities in the Eastern province of Saudi Arabia. During the study period, 165530 Saudi infants were born, of whom a total of 248 newborns were diagnosed with 55 IEM. Affected patients were evaluated based on clinical manifestations or family history of similar illness and/or unexplained neonatal deaths. Almost all patients were born to consanguineous parents. Fatty acid oxidation disorders were diagnosed in 18/248 patients (7%) and were suffering enzymatic deficiency. The diagnosis was confirmed in all fatty acid oxidation disorders by measuring the enzyme activity in blood or skin fibroblasts. Among them, three cases from a single family were found to have CACT deficiency. The estimated incidence of this condition was 2 in 100,000 live births. The authors concluded that data obtained from this study underestimate the true figures of various IEM in the region. Therefore, there is an urgent need for centralized newborn screening program that utilizes tandem mass spectrometry, and offers genetic counseling for these families.