Galactosemia

From Iusmgenetics

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[edit] Galactosemia

[edit] General background information

  • Galactosemia encompasses 3 autosomal recessive disorders: galactose 1-p uridyltransferase (GALT), galactokinase, epimerase
    • Galactokinase deficiency: 1 / 150K
    • Epimerase deficiency: rare
    • Note the locus heterogeneity
  • Galactosemia is a syndrome of galactose toxicity
  • Galactosemia incidence is 1 / 62K

[edit] Mode of inheritance

  • Autosomal recessive

[edit] Single important gene

  • There are actually three important enzymes that can cause galactosemia when defective: galactose 1-p uridyltransferase (GALT), Galactokinase, Epimerase
  • Galactosemia-pic.jpg

[edit] Etiology

  • Accumulation of two products cause disease states: Gal-1-P and Galactitol.
  • Depletion of UDP causes disease state, too.
  • Galactose-1-phosphate causes liver toxicity.
  • Galactitol causes cataracts.
  • Classic Galactosemia can be caused by two different alleles: the "inactive allele" or the "variant / Duarte allele" in galactose 1-p uridyltransferase (GALT)
    • Inactive allele: Gln188Arg
      • 70% of inactive alleles have this mutation
      • Allele frequency of 1/278
    • Variant / Duarte allele: Asn314Asp
      • causes 50% activity of the GALT
  • Compound heterozygotes (one inactive allele and one duarte allele) require treatment but only for the first year of life
  • Los Angeles alleles produce GALT with 140% activity and do not cause disease.
  • 43_2_73f4.gif

[edit] Pathogenesis

[edit] Phenotypic information

  • GALT deficiency: classic galactosemia:
    • Symptoms of galactosemia present soon after consumption of galactose-containing (milk or milk-based) foods:
      • Vomitting, refusal to feed, failure to thrive, lethargy, liver disease (hepatomegally, jaundice), cataracts, edema, sepsis, encephalopathy, developmental delay (mental retardation), seizures, brain damage
    • Note that brain damage is irreversible
    • Galactosemia is a serious, emergent newborn screening result.
      • May be fatal if left untreated.
      • Symptoms can begin to show even before the screen results have been returned.


  • Galactokinase deficiency
    • Mild
    • Catracts
    • No liver involvement
    • No mental retardation


  • Epimerase deficiency
    • Similar to classic galactosemia

[edit] Diagnosis

  • Galactosemia is part of the newborn screen.
    • There are two methods for screening: elevated galactose / gal-1-p levels in blood OR test for deficient GALT enzyme activity in RBCs
    • The GALT enzyme activity level is susceptible to heat exposure and false positives may arise.
    • However, GALT enzyme activity is accurate at any time but galactose / gal-1-p levels requires the ingestion of milk (otherwise it might generate a false negative).

[edit] Treatment

  • Galactose-free diet
    • Begin a galactose-free diet as soon as there is a suspicion of galactosemia--even if screening results aren't back yet.
    • Proper diet can reverse most newborn symptoms and prevent many sequelae (liver disease, mental retardation, cataracts).
  • IQ often declines with age
  • Females can have gonadal dysfunction
  • Many foods contain galactose (fruits and vegetables), thus, strict control is a long-term problem.

[edit] Recent research

[edit] 5 important facts

[edit] Not to be confused with

[edit] Questions and answers

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