A child suffered from viral illness for which he was given aspirin. Three days later the child was brought to the emergency with altered sensorium and icterus. What is the underlying biochemical defect?
Ans. a. Beta-oxidation of fatty acids A child suffered from viral illness for which he was given aspirin. Three days later the child was brought to the emergency with altered sensorium and icterus. Clinical picture mentioned in the question is highly suggestive of Reye's syndrome. Drugs (salicylates), toxins (aflatoxins), viral infections (varicella, influenza) and ceain inborn errors of metabolism (single enzyme defects of beta-oxidation) can precipitate Reye's syndrome 'Reye's syndrome: It is an acute self limiting metabolic insult of diverse etiology resulting in generalized mitochondrial dysfunction. Drugs (salicylates), toxins (aflatoxins), viral infections (varicella, influenza) and ceain inborn errors of metabolism (single enzyme defects of beta-oxidation) can precipitate Reye syndrome. Neuroglucopenia and hyperammonemia result from mitochondrial and sodium pump failure. Encephalopathy is secondary to the liver damage.'- Reye's Syndrome (Fatty Liver with Encephalopathy) is an acute self-limiting metabolic insult of diverse etiology resulting in generalized mitochondrial dysfunctiondeg. Acute illness, encountered exclusively in children < 15 yearsdeg Onset usually follows an upper respiratory tract infection, especially influenza or chickenpox Drugs (salicylates), toxins (aflatoxins), viral infections (varicella, influenza) and ceain inborn errors of metabolism (single enzyme defects of beta-oxidation) can precipitate Reye syndromedeg. Histopathology: Morphologically, extensive vacuolization of the liver and renal tubulesdeg. Mitochondria! dysfunction with decreased activity of hepatic mitochondrial enzymes with structural alterations of mitochondria in liver, brain and muscledeg In fatal cases, the liver is enlarged and yellowdeg with striking diffuse fatty microvacuolization of cells Extensive accumulation of fat droplets within hepatocytes (microvesicular steatosis) Major extra-hepatic changes are fatty changes of the renal tubular cells, cerebral edema and neuronal degeneration of the braindeg Clinical Features: Characterized clinically by: VomitingQ, signs of progressive CNS damageQ, signs of hepatic injuryQhypoglycemiaQ A mild prodromal illness is followed by acute onset of the disease. Seizures occur in more than 80% patients. There are few focal neurological or meningeal signs. The liver is enlarged, but jaundice is characteristically absent or minimalQ Clinical Features are described in Four Stages Stage I Vomiting, anorexia, mild confusion, listlessness, apathy Stage II Delirium, restlessness, irritability, lack of orientation, frightened,agitated states Stage Ill Coma, decoicate posture which later becomes decrebrate Stage IV Flaccidity, areflexia, apnea, dilated pupils not reacting to light,severe hypotension. Laboratory Findings in Reye's Syndrome Raised aminotranferases and PTQ Metabolic acidosisQ HypoglycemiaQ Elevated serum ammonia levelQ Treatment: Infusion of 20% glucose and fresh frozen plasmaQ I.V. mannitol to reduce cerebral edemaQ Prognosis: Moality rate: Approx. 50%Q
Beta-oxidation of fatty acids
Glucose-6-phosphatase deficiency
Pyruvate dehydrogenase deficiency
Urea cycle defect