Differentials
Extrahepatic biliary obstruction (e.g., choledochal cyst, spontaneous perforation of common bile duct, bile duct stricture or tumour, neonatal sclerosing cholangitis)
SIGNS / SYMPTOMS
Tumour or mass may be felt on palpation.
Spontaneous perforation can present with ascites or jaundice around the umbilicus associated with a tender abdomen.
Biliary strictures may form following liver transplantation.
INVESTIGATIONS
Ultrasound: may demonstrate tumour, bile duct dilation before a stricture, or a choledochal cyst.
Cholangiogram needed to differentiate from neonatal sclerosing cholangitis.
Hepatic viral infections (e.g., CMV, enterovirus, HSV, echovirus, adenovirus, hepatitis B virus, HIV, rubella, reovirus type 3, parvovirus B19, EBV)
SIGNS / SYMPTOMS
Infant may be septic or have petechiae and rashes.
Intracranial calcifications may be seen on cranial x-ray (periventricular calcifications).
INVESTIGATIONS
Viral serology.
Urine for CMV antigens, urine culture.
Viral swabs from nasal passages or rectum for enteroviruses.
Alagille syndrome
SIGNS / SYMPTOMS
Bile duct paucity, butterfly vertebrae, posterior embryotoxon (congenital eye abnormality), characteristic facies, cardiac/renal anomalies.
INVESTIGATIONS
Liver biopsy: paucity of bile ducts, or, if the child is young, the findings may show proliferation.
CXR: butterfly shape of vertebrae.
Echocardiogram: cardiac anomaly.
Facies: broad forehead, pointed chin.
Genetic testing for the JAG1 and/or NOTCH2 genes.
Alpha-1 antitrypsin deficiency
SIGNS / SYMPTOMS
Family history of lung disease at an early age.
INVESTIGATIONS
Alpha-1 antitrypsin serum level and protease inhibitor typing (blood test to look for protease inhibitor by gel electrophoresis).
Down syndrome
SIGNS / SYMPTOMS
Hypotonia, characteristic dysmorphic features.
INVESTIGATIONS
Karyotype: trisomy 21.
Turner syndrome
SIGNS / SYMPTOMS
Neonatal pedal oedema, lymphoedema.
Webbed neck.
INVESTIGATIONS
Karyotype: 45 X cell line or a cell line with deletion of the short arm of the X chromosome (Xp deletion).
Progressive familial intrahepatic cholestasis
SIGNS / SYMPTOMS
Clinical presentation indistinguishable but typically presents at about 3 months of age. May be family history.
INVESTIGATIONS
Liver biopsy: no inflammation, few bile ducts, giant cells may be seen, biliary epithelium apoptosis.
Multiple causative genes identified; genetic testing can be performed.
Congenital hepatic fibrosis and autosomal recessive polycystic kidney disease
SIGNS / SYMPTOMS
Renal insufficiency, hepatomegaly with predominant involvement of the left lobe.
Aminotransferase enzymes usually normal.
INVESTIGATIONS
Ultrasonography reveals evidence of intense hepatic echogenicity and evidence of portal hypertension.
Enlargement and polycystic changes of kidneys with increased echogenicity.
Caroli's disease
SIGNS / SYMPTOMS
Fever if cholangitis is present, abdominal pain, nausea and vomiting, mass if large polycystic kidneys.
INVESTIGATIONS
Ultrasonography: cystic lesions and intrahepatic bile duct dilation.
Magnetic resonance cholangiography: irregular dilation of the large intrahepatic bile ducts.
North American Indian childhood cirrhosis
SIGNS / SYMPTOMS
Severe familial neonatal cholestasis only described in North American Indian children. May present with bleeding varices.
INVESTIGATIONS
Genetic testing: missense mutation of the cirhin gene, found on chromosome 16q22.
Rotor syndrome
SIGNS / SYMPTOMS
May have episodes of fever, intermittent abdominal pain described, chronic jaundice, not itchy.
INVESTIGATIONS
Elevated conjugated and non-conjugated bilirubin with normal transaminases and excretion of tracer during hepatobiliary scintigraphy.
Urine coproporphyrin ratios and normal liver histology.
Dubin-Johnson syndrome
SIGNS / SYMPTOMS
Presentation with jaundice.
Tends to present later in childhood.
INVESTIGATIONS
Elevated bilirubin but with normal transaminases.
Increased ratio of urinary coproporphyrin I to coproporphyrin III.
Intense and prolonged visualisation of the liver with delayed or absent visualisation of the gallbladder on hepatobiliary scintigraphy scan.
Cystic fibrosis
SIGNS / SYMPTOMS
Faltering growth, excessive mucus production, lung infections, fatty diarrhoea, meconium ileus.
INVESTIGATIONS
Elevated sweat chloride, cystic fibrosis transmembrane conductance receptor gene mutations.
Hypothyroidism
SIGNS / SYMPTOMS
Poor feeding, constipation, hypothermia.
INVESTIGATIONS
Thyroid function tests: low levels of T4 with high levels of TSH.
Predominantly unconjugated hyperbilirubinaemia.
Panhypopituitarism
SIGNS / SYMPTOMS
Midline malformations, nystagmus, hypoglycaemia.
INVESTIGATIONS
Hormonal tests show reduced levels of pituitary hormones.
Neurological imaging: abnormality of pituitary gland (appearance will depend on cause for reduced pituitary function).
Galactosaemia
SIGNS / SYMPTOMS
Vomiting and faltering growth, congenital cataracts, may have associated Escherichia coli sepsis.
INVESTIGATIONS
Positive urine reducing substances. Reduced RBC galactose-1-phosphate uridyl transferase activity.
Hereditary tyrosinaemia
SIGNS / SYMPTOMS
Faltering growth, coagulopathy, distinctive cabbage-like odour.
INVESTIGATIONS
Elevated succinylacetone in blood or urine.
Niemann-Pick disease
SIGNS / SYMPTOMS
Hepatosplenomegaly usually without liver dysfunction, faltering growth, and hypotonia.
INVESTIGATIONS
Cherry-red spot on ophthalmological examination.
Decreased acid sphingomyelinase activity in peripheral blood WBCs or cultured fibroblasts.
Wolman's disease
SIGNS / SYMPTOMS
Severe hepatomegaly, faltering growth, vomiting, diarrhoea, splenomegaly, and ultimately liver failure.
INVESTIGATIONS
Liver biopsy: fatty infiltration.
Lysosomal acid lipase deficiency.
Hereditary fructose intolerance
SIGNS / SYMPTOMS
Onset of symptoms coincides with introduction of fructose-containing formula or foods.
INVESTIGATIONS
Molecular analysis of aldolase B gene.
Glycogen storage disease IV
SIGNS / SYMPTOMS
Can present in infancy with hepatosplenomegaly, cirrhosis, and liver dysfunction.
INVESTIGATIONS
Liver biopsy: excessive abnormal glycogen storage.
Muscle biopsy: branching enzyme deficiency detected by polyglucosan inclusions.
Mitochondrial disorders
SIGNS / SYMPTOMS
Neonatal liver failure, lactic acidosis, seizures.
INVESTIGATIONS
Elevated blood lactate-pyruvate ratio.
Electron microscopy of liver biopsy: evidence of abnormal mitochondria.
Genetic testing for specific defects.
Peroxisomal disorders (e.g., Zellweger's, infantile Refsum disease, mevalonate kinase deficiency)
SIGNS / SYMPTOMS
Craniofacial and neurological abnormalities in association with jaundice.
INVESTIGATIONS
Best initial test is plasma very long-chain fatty acid analysis by gas chromatography.
Bile acid synthesis defects
SIGNS / SYMPTOMS
Hepatosplenomegaly.
INVESTIGATIONS
Normal gamma-glutamyl transferase, elevated transaminases.
Urinary bile acid analysis by fast atom bombardment ionisation mass spectrometry.
Toxic causes: drugs, total parenteral nutrition, endotoxin from gram-negative bacteria
SIGNS / SYMPTOMS
Onset of jaundice related to timing of exposure to toxin.
May be systemically unwell with fever and rash.
INVESTIGATIONS
No specific test. Relies on temporal relationship and treatment of suspected cause (e.g., sepsis, cessation of total parenteral nutrition or drug, and resolution of symptoms) to confirm diagnosis.
Sepsis
SIGNS / SYMPTOMS
Onset of jaundice related to timing of exposure to toxin.
May be systemically unwell with fever and rash.
INVESTIGATIONS
No specific test. Relies on temporal relationship and treatment of suspected sepsis to confirm diagnosis.
Idiopathic neonatal hepatitis
SIGNS / SYMPTOMS
Clinically indistinguishable.
INVESTIGATIONS
Liver biopsy shows giant cell transformation.
Ischaemia-reperfusion injury
SIGNS / SYMPTOMS
Typically occurs after an infant has been profoundly ill.
INVESTIGATIONS
Liver biopsy shows centrilobular injury with periportal preservation.
Inspissated bile
SIGNS / SYMPTOMS
Clinically indistinguishable.
May be found in cystic fibrosis or after significant haemolysis.
INVESTIGATIONS
Ultrasound of bile ducts: intrabiliary bile plugs.
Congenital heart disease
SIGNS / SYMPTOMS
Cyanosis, low oxygen levels, low blood pressure, known cardiac defects.
INVESTIGATIONS
Echocardiogram: will determine cardiac anomalies.
Use of this content is subject to our disclaimer