What is the diagnosis of an infant presenting with cataracts, hepatomegaly (enlarged liver), and liver failure?

Diagnosis: Galactosemia

An infant presenting with cataracts, hepatomegaly, and liver failure should be immediately evaluated for galactosemia, as this is the classic triad that defines this treatable metabolic emergency. 1

Why Galactosemia is the Primary Diagnosis

• Cataract is pathognomonic for galactosemia when combined with hepatomegaly and liver failure in infancy, as this ocular finding plays an important diagnostic role that distinguishes galactosemia from other metabolic liver diseases 1

• Galactosemia is one of the most commonly implicated metabolic liver diseases causing acute liver failure in young infants, accounting for 13-43% of metabolic causes 2

• The combination of these three features (cataracts + hepatomegaly + liver failure) creates a highly specific clinical pattern that should trigger immediate diagnostic testing 1

Immediate Diagnostic Workup

Obtain the following tests urgently:

• Urine reducing substances (positive with negative glucose oxidase test indicates galactosuria) 2
• Red blood cell galactose-1-phosphate uridyltransferase (GALT) enzyme activity - this is the definitive diagnostic test 2
• Plasma amino acids to check for elevated tyrosine (to rule out tyrosinemia, another common cause) 3, 2
• Urine succinylacetone to exclude tyrosinemia type I 3
• Liver synthetic function tests (PT, PTT, albumin, bilirubin) to assess severity 3

Critical Management Principles

Immediately eliminate all galactose/lactose from the diet while awaiting confirmatory testing, as simple dietary modification can be life-saving if instituted promptly 2

• Stop all milk feeds (breast milk and standard formula contain lactose) 2
• Switch to soy-based or lactose-free formula 2
• Provide supportive care for liver failure including vitamin K administration for coagulopathy 3

Key Differential Diagnoses to Exclude

While galactosemia is most likely, also consider:

• Tyrosinemia Type I: Presents with hepatomegaly and liver failure but typically without cataracts; diagnosed by elevated succinylacetone 3
• Alpha-1 antitrypsin deficiency: Presents at 1-2 months with hepatomegaly and coagulopathy, but cataracts are not a feature 3
• Neutral lipid storage disease: Rare disorder that can present with hepatomegaly, cataracts, and myopathy, but liver failure is not prominent 4

Critical Pitfalls to Avoid

• Do not delay dietary galactose elimination while awaiting enzyme testing results, as continued galactose exposure worsens hepatic and neurologic damage 2
• Do not assume vitamin K deficiency alone explains the coagulopathy - this represents true hepatic synthetic dysfunction requiring urgent metabolic evaluation 3
• Do not miss the ophthalmologic examination - cataracts may be subtle in early stages and require slit-lamp examination for detection 1

Prognosis and Long-term Considerations

• Early diagnosis and prompt dietary galactose restriction can prevent progression of liver failure and allow hepatic recovery 2
• Even with treatment, long-term complications including developmental delays and ovarian failure (in females) may occur 2
• Liver transplantation is rarely needed if dietary management is instituted early 2