Thursday, December 23, 2010

Clinical Case: Newborn With Severe Acidosis, Vomiting, Hypotonia, and Neurologic Deficits

Clinical Vignette: A newborn presents with severe acidosis, vomiting, hypotonia, and neurologic deficits. Serum analysis reveals elevated levels of lactate and alanine. These observations suggest a deficiency in which of the following enzymes? 

            A. Alanine aminotransferase  
            B. Glutamate dehydrogenase 
            C. Lactate dehydrogenase 
            D. Pyruvate carboxylase  
            E. Pyruvate dehydrogenase 


         The correct answer is E. A common Biochem clinical vignette. Pyruvate dehydrogenase (PDH) catalyzes the irreversible conversion of pyruvate to acetyl-CoA. If PDH is absent, pyruvate will be used in other pathways instead. Pyruvate will be converted to alanine via alanine aminotransferase (choice A) and to lactate via lactate dehydrogenase (choice C). 

         Glutamate dehydrogenase (choice B) is involved in oxidative deamination, releasing ammonium ion for urea synthesis. Deficiency of this enzyme would not cause the symptoms described. 

         Pyruvate carboxylase (choice D) is a gluconeogenic enzyme that catalyzes the conversion of pyruvate to oxaloacetate. Deficiency of this enzyme would not cause the symptoms described.