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The most common form of galactosemia is caused by deficiency in GALT. ... .org 'Galactosemia Signs and Symptoms' John Goldenring, MD, MPH, JD, Department ... – PowerPoint PPT presentation

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Title: Galactosemia

  • PHM226 Presentation
  • 5 March 2008
  • Anne Wilbur, Brenna Hanwell,
  • Saeed Tavakoli and Sassha Orser

What is Galactose?
  • Galactose is a sugar that is found in many foods.
  • Lactose is a sugar that is found in many foods.
    When lactose is broken down in the body, glucose
    and galactose are produced.
  • Foods that contain galactose and lactose include
    fruits, vegetables, legumes, organ meats,
    processed meats and sandwich meats, milk and
    dairy products, coffee

What is Galactose?
What is Galactosemia?
  • Galactosemia is an inherited metabolic disorder
    that is caused by impaired metabolism of
    a-D-galactose in the body
  • The most common form of galactosemia is caused by
    deficiency in GALT. The incidence of this form is
    1/30,000 to 1/60,000 live-births. This is also
    the most clinically severe form of the disease.

Galactose Metabolism - Leloir
Galactose Metabolism - Leloir
  • a-D-galactose is metabolized in species ranging
    from E.coli to humans
  • predominantly metabolized through the Leloir
    Pathway which involves three enzymes
  • Galactokinase (GALK) phosphorylates
    a-D-galactose to produce gal-1-P
  • Galactose-1-phosphate uridylyl transferase
    (GALT) transfers UMP from UDP-glucose to gal-1-P
    to release glucose 1-phosphate and produce
  • UDP-galactose 4-epimerase (GALE) interconverts
    UDP-galactose and UDP-glucose
  • Deficiency of any one of these enzymes can lead
    to a form of galactosemia
  • Classical galactosemia is caused by profound
    impairment of the GALT enzyme

Galactose Metabolism - Alternate
Galactose Metabolism - Alternate
  • There are also three non-Leloir enzymes involved
    in the metabolism of galactose
  • Conversion of galactose to UDP-glucose by the
    sequential activities of GALK, UDP-glucose/galacto
    se pyrophosphorlyase (UGP) and GALE
  • Reduction of galactose to galactitol by aldose
  • Oxidation of galactose to galactonate by
    galactose dehydrogenase
  • Under normal circumstances the non-Leloir enzymes
    metabolize minimal amounts of galactose but with
    failure of the Leloir pathway these alternative
    pathways may become more significant
  • These alternative pathways may
  • Limit accumulation of toxic intermediates
  • Cause accumulation of other end products that are
    also problematic

  • Abnormal production and accumulation and/or
    depletion of specific metabolites leads to the
    characteristic symptoms of galactosemia
  • Galactose
  • Galactose-1-phosphate (gal-1-P)
  • Galactitol (accumulation in lens cells leads to
  • Inositol
  • Galactonate (does not accumulate in tissue due to
    excretion in urine)
  • UDP-galactose (partially depleted in RBCs)

Signs Symptoms
  • At birth, galactosemia is usually asymptomatic.
  • Escalating symptoms develop after exposure to a
    milk-based diet.
  • Symptoms include vomiting, diarrhea, cataracts,
    hepatomegaly, and E. coli sepsis. Without
    treatment, these symptoms can lead to neonatal
  • Even with treatment, long-term complications such
    as speech and cognitive disabilities in 30-50 of
    patients, primary or premature ovarian failure in
    85 of females, ataxic neurologic disease,
    delayed growth and decreased bone density can

Signs Symptoms
  • Prenatal diagnosis by direct measurement of the
    enzyme galactose-1-phosphate uridylyl transferase
  • The presence of "reducing substances" in the
    infant's urine with normal or low blood sugar
    while the infant is being fed breast milk or a
    formula containing lactose. A simple test on the
    urine indicates the presence of a reducing
    substance, and a specific enzymatic study on the
    urine can prove the substance to be galactose.
  • Normal range for Galactose-1-phosphate uridylyl
    transferase is18.5 to 28.5 U/g Hb.
  • Other methods for diagnosis include
  • Galactose Tolerance
  • Eryrthrocyte Assay for Gal-1-P Uridylyl
  • White Blood Cell Assay for Gal -1-P Uridylyl
  • Amniocentesis

  • Individuals with galactosemia must remain on a
    restricted diet and maintain low blood galactose
    levels throughout life.
  • There is no treatment per se for galactosemia.
  • However, lethal and toxic events of galactosemia
    can be prevented by dietary interventions.
  • Therefore it is extremely important that early
    diagnosis is made.
  • Genetic screening is done in utero (ex. if there
    is family history) or post-partem in many states
    and provinces

  • The dietary intervention, technically sounds
    simple to avoid lactose and galactose.
  • However, so many foods (and medications) contain
    lactose and galactose that it is hard to avoid
    it. Some common examples are
  • ANYTHING with milk ingredients (milk, butter,
    cheese, yogurt, etc)
  • Organ meat such as liver, heart, and pancreas.
  • Margarine (some contain no milk products, so
    checking label is key however, any other product
    that has margarine as an ingredient is assumed to
    have lactose in it)
  • MSG (some contain lactose extenders)
  • Fermented soy sauce
  • Hydrolized protein (i.e. canned tuna)
  • Coffee
  • Legumes, peas, tomatoes, hazelnuts
  • Dried figs, grapes, papaya, pineapple,
    watermelon, blueberries.
  • Goal is to keep blood gal-1-p level below 3 to 4
    mg/100 mL

Pharmaceutical Applications
  • Lactose is a common excipient used in oral
    medication dosage forms.
  • Children with galactosemia often require
    medications to treat conditions associated with
    the disease, such as tremors, ovarian failure and
  • These children will also require treatment for
    other common childhood diseases.
  • Lilac pages in the Clin-Info section of the CPS
    contain information regarding medications
    containing lactose.
  • If this information is not in the CPS, can
    contact the manufacturer for more information.
  • Calcium supplementation also a concern,
    especially since many supplements contain
  • Suggestions for Calcium supplementation liquid
    calcium/magnesium combinations, Caltrate brand
    chewable calcium tablets.

Pharmaceutical Applications
Future Research
  • Current treatment focuses on eliminating
    galactose from the diet and treating the
    conditions associated with disease.
  • Continued focus on understanding all aspects of
    the disease including how the disease causes
    associated conditions, such as behavioural
  • Possible gene therapy.
  • The alternative pathways, and the genes and
    enzymes that comprise them, are logical targets
    for small molecule therapeutic intervention and
    potential modifiers of patient outcomes

  • Galactosemia is an inherited condition, where the
    affected individual cannot properly breakdown
  • Galactose is a sugar that forms during the
    breakdown of lactose.
  • Galactose is metabolized by three different
    enzymes GALT, GALK, GALE.
  • There are three different forms of galactosemia,
    which affect different parts of the enzymes in
    galactose metabolic pathway. The most common form
    is caused by a deficiency in GALT.
  • Inability to breakdown galactose leads to a
    build-up of toxic metabolites.
  • The build-up of these toxic metabolites can lead
    to conditions in the body, such as tremors,
    ovarian failure, and behavioural abnormalities.
  • There is not treatment for galactosemia, the
    associated conditions can be prevented, to a
    certain extent by adherence to strict dietary
  • Dietary restrictions include milk and milk
    products, organ meats, grapes among many other
  • Patients also must be aware of hidden sources of
    lactose, such as excipients in medications.
  • The pharmacist can play a role in being aware of
    prescription medications containing lactose, and
    supplements that most suit the patients needs.

  • Yi-Hung Hsia, D. et. al. Galactosemia
    Northwestern Medical School Printing 1969
    Springfield Illinois
  • Parents of Galactosemic Children Last update 2007.
  • Washington State Department of Health Newborn
    Screening http//
    n/galgo.htmq4 Last updated 11/20/2006
  • Chemfinder Cambridge Software
  • United States Library of Medicine Genetics Home
    Reference http//
    osemia Last updated January 2008.
  • BioCarta The Pathway of Glucose Metabolism
    1pPathway/h_g1pPathway.gif Last update June 2007
  • National Academy of Science Earth and Life
    Sciences Pathway of Galactose Breakdown
    3f4.gif Last Updated 2007
  • Medline Plus Galactosemia Signs and
    Symptoms John Goldenring, MD, MPH, JD,
    Department of Pediatrics, Children's Hospital,
    San Diego, CA
  • CPS
  • Fridovich-Kiel, J. Galactosemia the Good, the
    Bad, and the Unknown Journal Of Cellular
    Physiology 209701705 (2006)

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