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Internal Medicine

Galactosemia

Rare inborn error of metabolism due to impaired degradation of galactose.

Rare inborn error of metabolism due to impaired degradation of galactose.

  • Autosomal recessive inheritance
  • D/t galactose-1-phosphate uridyltransferase (GALT/GALPUT) deficiency

Pathophysiology

Three different enzymes are involved in the metabolism of galactose include galactose-1-phosphate uridyltransferase (GALT), galactokinase, and epimerase.

Galactosemia is caused by deficient activity of GALT, the second enzyme of the Leloir pathway.

Galactose metabolism. In the Leloir pathway, galactose is converted to glucose-1-phosphate (Glc-1-P) by the action of three consecutive enzymes: galactokinase (GALK1), galactose-1-phosphate uridylyltransferase (GALT), and UDP-galactose 4′-epimerase (GALE). Alternatively, galactose can be reduced to galactitol by aldose reductase, oxidized to galactonate, presumably by galactose dehydrogenase, or be converted into UDP-Glc, via the pyrophosphorylase pathway, by the sequential activities of GALK1, UDP-glucose/galactose pyrophosphorylase (UGP), and GALE. GALE is also responsible for the interconversion of UDP-N-acetylgalactosamine to UDP-N-acetylglucosamine (not shown). PPi, pyrophosphate | Coelho, A. I., Rubio-Gozalbo, M. E., Vicente, J. B., & Rivera, I. (2017). Sweet and sour: an update on classic galactosemia. Journal of inherited metabolic disease, 40(3), 325–342. https://doi.org/10.1007/s10545-017-0029-3
  • Increased galactose-1-phosphate accumulates in the liver, kidney, brain, tongue, lens, and cutaneous fibroblasts, and causes injury. In many patients
  • Rapid symptom regression occurs with early initiation of treatment, but outcomes that affect life negatively in the short and long term may be observed

Clinical features

These present following intake of galactose in the neonatal period:

  • Hepatocellular damage: Jaundice (M/C, 86% cases), hepatosplenomegaly, hepatic failure
  • Feeding difficulties
  • Failure to thrive
  • Hypoglycemia
  • Renal tubular dysfunction
  • Muscular hypotonia
  • Oil drop cataracts (accumulation of galactriol in lens)
  • E coli sepsis in untreated infants

Diagnosis

Urinary sugar tests:

  • Benedict’s test (+): Reducing sugar present
  • Mucic acid test (+): Galactose specific test

Enzyme assays:

  • ↑ Erythrocyte galactose-1-phosphate
  • ↓ Erythrocyte galactose-1-phosphate uridylyltranserase (GALT) enzyme activity

Management

Lactose-restricted diet followed by long-term diet therapy:

First ten days of life, the severe acute neonatal complications are usually prevented
  • Breastmilk, cow’s milk, and formulas contain a significant amount of lactose thus galactose; therefore, they should not be given to these patients.
  • In infancy, formulas containing lactose-free casein hydrolysates or separated oligosaccharides can be used.

Exogenous calcium and vitamin D supplementation:

Prevent reduction in bone mineralization in patients with galactosemia

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