galactosemia
Summary
Galactosemia is an autosomal recessive metabolic disorder most commonly caused by deficiency of galactose-1-phosphate uridyltransferase (GALT), leading to accumulation of toxic galactose metabolites. Classic presentation includes failure to thrive, jaundice, hepatomegaly, vomiting, and E. coli sepsis in a neonate after breast/formula milk feeding. Treatment is lifelong exclusion of galactose and lactose from the diet.
Detail
Galactosemia results from impaired conversion of galactose to glucose. The classic and most severe form is due to deficiency of galactose-1-phosphate uridyltransferase (GALT), causing accumulation of galactose-1-phosphate, which is toxic to the liver, kidney, and brain. A milder form is caused by galactokinase (GALK) deficiency, which leads to galactitol accumulation and cataracts but lacks the severe hepatic and neurologic findings.
Pathophysiology: In classic galactosemia (GALT deficiency), galactose-1-phosphate accumulates in the liver, kidney, and lens, causing hepatotoxicity, renal tubular dysfunction (Fanconi-like syndrome), and cataracts (from galactitol formed via aldose reductase). CNS effects lead to intellectual disability if untreated.
Clinical presentation: Infants appear normal at birth but develop symptoms after starting breast milk or lactose-containing formula (lactose = glucose + galactose). Symptoms include vomiting, diarrhea, poor feeding, failure to thrive, jaundice/hepatomegaly (hepatocellular damage progressing to cirrhosis), cataracts, and increased susceptibility to E. coli neonatal sepsis (galactose interferes with leukocyte bactericidal activity). Long-term complications despite dietary treatment include ovarian failure, speech/language deficits, and neurologic issues.
Diagnosis: Newborn screening detects elevated blood galactose and reduced GALT enzyme activity. Urine testing shows reducing substances (positive Clinitest but negative glucose oxidase test, distinguishing it from glucosuria).
Management: Immediate removal of galactose and lactose from diet (switch to soy-based formula). Early treatment prevents hepatic and cataract complications but may not fully prevent long-term cognitive and ovarian issues.
Genetics: Autosomal recessive; GALT gene mutations on chromosome 9p13.
High-yield boards points: Differentiate from other reducing substance disorders; classic vignette involves neonatal sepsis with E. coli after starting feeds, along with jaundice and hepatomegaly; distinguish from fructose intolerance (which presents after fruit introduction, not milk).
Sources
- First Aid for the USMLE Step 1
- Harrison's Principles of Internal Medicine
- Nelson Textbook of Pediatrics
- UpToDate: Galactosemia
Reviewed by AnkiBoss editorial — medical student review. Information here is for study reference only and is not medical advice. Spotted an error? Let us know.