Dr Ira Shah
M.D, DNB, DCH(Gold Medalist), FCPS

A 13 month old female child born of third degree consanguineous marriage presented with loose motions and abdominal distension since 2 days and hematemesis, vomiting and lethargy since 1 day. On examination she had altered sensorium with brisk reflexes. She had no meningeal signs or icterus. She had a tender hepatomegaly and other systemic examination was normal. Her birth history was uneventful and other 2 siblings were normal. Her milestones prior to this episode were normal. There was no history of drug ingestion or skin rash. She was suspected to have Reye’s syndrome and investigations revealed raised liver enzymes (SGOT = 9120 IU/L, SGPT = 6140 IU/L) with hyperammonemia [S.NH 3 = 143 mcg/al (Normal = 30-90 mcg/dl)] and hypoglycemia (Random blood sugar = 25mg/dl)]. Her S.Bilirubin was normal and prothrombin time and PTT were deranged. Thus she was diagnosed as Reye’s syndrome. She was treated with fresh frozen plasma, IV antibiotics and lactulose. Her Anti HAV IgM, HBsAg, Dengue IgM & Leptospira IgM & IgG were negative. Her blood gases revealed metabolic acidosis with bicarbonate of 13.3 MEq/L. In view of Reye’s syndrome without any precipitating cause, an underlying inborn error of metabolism was considered. A liver biopsy was considered but in view of her clinical instability it was not done. Her Serum Carnitine was 1.5 mmoles/L (Normal = 20-43 mmoles/L) and S.lactate was 28.1 mg/dl (Normal = 5.7-22 mg/dl) and S.pyruvate was 0.29 mg/dl (Normal = 0.36 – 0.59 mg/dl) with a lactate: pyruvate ratio of 96.9 which was elevated. Her 2 D Echo also showed mild to moderate pulmonary hypertension. Thus, she was diagnosed as a mitochondrial disorder and treated with Thiamine & Carnitine. and discharged. On follow up after a month, she had regained all her milestones and liver enzymes were normal and blood sugar & blood gases were also normal.

Reye’s syndrome is characterized by acute encephalopathy and fatty degeneration of the liver. The CDC now define Reye syndrome as an acute non-inflammatory encephalopathy (alteration in level of consciousness, no CSF pleocytosis and, if biologic examination is possible. cerebral edema without meningeal or perivascular inflammation) associated with “microvesicular fatty metamorphosis of the liver” (confirmed by biopsy or autopsy) or a significant rise (threefold or greater) of serum transaminases or blood ammonia, and having “no more reasonable explanation” for the cerebral and hepatic abnormalities. The disorder is associated with salicylate ingestion and influenza B virus. An increasing number of inherited mitochondrial metabolic diseases have been described that produce episodes like Reye’s syndrome of which the main disorders are disorders of fatty acid oxidation, disorders of oxidative phosphorylation, urea cycle defects, organic acidurias and general mitochondrial dysfunction. The pathophysiology involves generalized loss of mitochondrial function leading to disturbances in fatty acid and carnitine metabolism.

“Classic” Reye’s syndrome was seen with influenza B and varicella infection in children between 4-12 years of age. It has a stereotypic biphasic course. When the child is seemingly recovering from a prodromal febrile illness, abrupt onset of protracted vomiting occurs. Delirium, combative behavior and stupor may occur simultaneously or within few hours after onset of vomiting. Neurologic symptoms may rapidly progress to seizures, coma and death (focal neurologic signs are absent). There is a mild hepatomegaly and patients remain anicteric. There is increase in serum aminotransferases, creatine kinase and lactic dehydrogenase with hyperammonia. Younger patients have hypoglycemia (they should be screened for metabolic disease). Biopsy may be required to rule out metabolic or toxic liver disease especially in patients younger than 1-2 years. The major site of injury is the mitochondria. The hepatic intramitochondrial enzymes including ornithine transcarbamylase (OTC), carbamoylphosphate synthetase (CPS) and pyruvate dehydrogenase are reduced leading to hyperammonemia. Aspirin has been found to be associated with this mitochondrial dysfunction and it is prudent to avoid aspirin in patients with varicella or influenza. A child with Reye’s syndrome should be screened for metabolic disorder and baseline urinary organic acid, serum and urine carnitine, urinary ketones, serum free fatty acids, serum amino acids and serum lactate and pyruvate are necessary. Specialized tests such as Long chain fatty acid loading test, protein load test, urinary orotic acid and enzymatic analysis may be required as necessary. Treatment consists of control of increased intracranial pressure, glucose administration and management of coagulopathy. Pentobarbital may have a protective effect on the CNS by decreasing cerebral metabolic demands, decreasing cerebral blood flow and causing cerebral vasoconstriction.