PMC:1189074 / 2130-4338 JSONTXT

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Inherited MCAD deficiency exists in humans as an autosomal recessive disorder. MCAD deficiency was first described in 1982—1983 [5–7] and has been described in numerous patients [1,8–11]. The carrier frequency in the Caucasian population has been estimated to be between 1 in 50 to 80 with an incidence of clinical disease expected at around 1 in 15,000 [1,9,12].\nMCAD-deficient patients exhibit clinical episodes often associated with fasting. Patients manifest disease usually during the first two years of life. Symptoms include hypoketotic hypoglycemia and Reye-like episodes [1]. It is estimated that approximately 59% of patients presenting clinically between 15 to 26 mo of age die during their first clinical episode [1].\nThe pathogenesis of the wide range of metabolic disturbances in MCAD deficiency is poorly understood and certain aspects of patient management are controversial. An animal model for MCAD deficiency is essential to better understand the pathogenesis of MCAD deficiency and to develop better management regimens for human patients. To gain further insight into the mechanisms of this disease, we developed a mouse model of MCAD deficiency by gene targeting in embryonic stem (ES) cells (for reviews [13,14]). The mutant mice had many relevant features characteristic of the disease found in human MCAD-deficient patients, along with some unexpected 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