Patterson JK, et al. An unusual cause of failure to thrive in an infant with vomiting and elevated transaminases. Clin Pediatr (Phila). 2014 Nov; 53(13):1299-301.
“Failure to thrive is a common indication for hospital admission during infancy and early childhood. In a case series of 185 patients with admission for failure to thrive, only 18% had a serious underlying medical condition, and the cause in all cases was strongly suggested by history and physical examination alone.1 Therefore, recent consensus has been for limited laboratory investigation of these infants, as the majority of tests are nondiagnostic. Clues suggestive of an underlying inborn error of metabolism include a history of severe, potentially life-threatening symptoms (such as apparent life-threatening events or sepsis), recurrent vomiting, signs or symptoms of liver or renal dysfunction, cardiomyopathy, myopathy, abnormal neurologic examination, or dysmorphic facies.2 In this case, the patient displayed recurrent vomiting and evidence of liver dysfunction, prompting further evaluation.
Malabsorption is an important potential cause of failure to thrive and can be because of malabsorption of carbohydrates, protein, and/or fat. Fat malabsorption, which was documented in this case, can be further subcategorized into pancreatic insufficiency, disorders of bile acid synthesis or excretion, and metabolic disorders that affect transport/processing of ingested fat.3 In our case, the voluminous diarrhea after hospitalization led to fecal fat testing. The normal stool elastase argued against pancreatic insufficiency, and there were no features suggestive of bile acid disorders, raising a metabolic fat transport disorder, of which abetalipoproteinemia is the prototype example, as a more likely diagnosis.”
Wright MA, et al. Consider muscle disease in children with elevated transaminase. J Am Board Fam Med. 2012 Jul-Aug; 25(4) :536-40.
The transaminases alanine aminotransferase (ALT) and aspartate aminotransferase (AST) are markers of hepatocellular injury but are highly concentrated in muscle cells. Consequently, muscular dystrophies such as Duchenne muscular dystrophy, lead to hypertransaminasemia. Elevation in ALT and AST is most striking during the early stages of disease, before onset of or when only subtle signs of muscle disease are present. Thus, the incidental finding of elevated ALT/AST may be the presenting sign of muscle disease in many children and provides an opportunity for early diagnosis. Many physicians, however, pursue extensive workup for liver disease in children who present with the incidental finding of elevated ALT/AST. This results in delayed diagnosis and initiation of treatment and increased expense and may lead to unnecessary invasive procedures. We report 12 patients with muscle disease who presented with a variety of symptoms and were found to have an incidental finding of elevated ALT/AST. We propose a rapid screening process for evaluating children with the incidental finding of elevated ALT/AST to shorten the time to diagnosis of muscle disease.
Fellman V, Kotarsky H. Mitochondrial hepatopathies in the newborn period. Semin Fetal Neonatal Med. 2011 Aug;16(4):222-8.
Mitochondrial disorders recognized in the neonatal period usually present as a metabolic crisis combined with one or several organ manifestations. Liver disorder in association with a respiratory chain deficiency may be overlooked since liver dysfunction is common in severely sick newborn infants. Lactacidosis, hypoglycemia, elevated serum transaminases and conjugated bilirubin are common signs of mitochondrial hepatopathy. Hepatosplenomegaly may occur in severe cases. A clinical picture with fetal growth restriction, postnatal lactacidosis, hypoglycemia, coagulopathy, and cholestasis, especially in combination with neurological symptoms or renal tubulopathy, should alert the neonatologist to direct investigations on mitochondrial disorder. A normal lactate level does not exclude respiratory chain defects. The most common liver manifestation caused by mutated mitochondrial DNA (deletion) is Pearson syndrome. Recently, mutations in several nuclear DNA genes have been identified that lead to mitochondrial hepatopathy, e.g. mitochondrial depletion syndrome caused by DGUOK, MPV17, SUCLG1, POLG1, or C10ORF2 mutations. A combination of lactacidosis, liver involvement, and Fanconi type renal tubulopathy is common when the complex III assembly factor BCS1L harbors mutations, the most severe disease with consistent genotype-phenotype correlation being the GRACILE syndrome. Mutations in nuclear translation factor genes (TRMU, EFG1, and EFTu) of the respiratory chain enzyme complexes have recently been identified. Diagnostic work-up of neonatal liver disorder should include assessment of function and structure of the complexes as well as mutation screening for known genes. So far, treatment is mainly symptomatic.
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Iorio R, et al. Hypertransaminasemia in childhood as a marker of genetic liver disorders. J Gastroenterol. 2005 Aug; 40(8): 820-6.
During the first 6 months of observation, 259 children showed normalized liver enzymes. Among the remaining 166 patients with hypertransaminasemia lasting for more than 6 months, 75 had obesity-related liver disease; 51, genetic disorders; 7, autoimmune hepatitis; 5, cholelithiasis; 3, choledochal cyst; and 3, celiac disease. Among the 51 children with genetic disorders, 18 had Wilson disease; 14, muscular dystrophy; 4, alpha-1-antitrypsin deficiency; 4, Alagille syndrome; 4, hereditary fructose intolerance; 3, glycogen storage disease (glycogenosis IX); 2, ornithine transcarbamylase deficiency; and 2, Shwachman’s syndrome. In 22 children, the hypertransaminasemia persisted for more than 6 months in the absence of a known cause.
Genetic disease accounted for 12% of cases of isolated hypertransaminasemia observed in a tertiary pediatric department. A high level of suspicion is desirable for an early diagnosis of these disorders, which may present with isolated hypertransaminasemia and absence of typical clinical signs.
More PubMed results on elevated transaminases.