WHAT IS GALACTOSEMIA?

Galactosemia, which means galactose in the blood, is a rare inherited condition. People with galactosemia have
problems digesting a type of sugar called galactose from the food they eat. Because they cannot break galactose
down properly, it builds up in their blood. Galactose is found in milk and all foods that contain milk.

WHAT CAUSES GALACTOSEMIA?

In order for the body to use different types of carbohydrates and sugars from the food we eat, special enzymes break
them down into smaller sugar molecules called glucose, which the body uses for fuel.
Lactose, also called milk sugar is the main type of sugar found in milk and milk products. It is made of one molecule
of galactose and one molecule of glucose. Thus, all lactose, and all milk and milk products, contain galactose.
During digestion, lactose is broken down to galactose and glucose. Then galactose is further changed by the body
into glucose so it can be used as energy.
Galactosemia occurs when an enzyme, called galactose-1-phosphate uridyl transferase (GALT) is either missing or
not working properly. This enzymes job is to change galactose into glucose. When the GALT enzyme is missing or
not working properly, galactose cannot be changed to glucose so it builds up in the blood in large amounts. Unless
treated, the excess galactose will affect many parts of the body and, over time, may be life-threatening.
Galactosemia
Galactosemia occurs when babies do not have enough of the GALT enzyme. Babies start showing health effects
within days of feeding on breast milk or milk-containing formulas. Virtually all cases of classic galactosemia can be
detected by newborn screening.
does not contain information on Duarte galactosemia or other variants.

WHAT IS GALACTOSEMIA?
Galactosemia, which means galactose in the blood, is a rare inherited condition. People with galactosemia have
problems digesting a type of sugar called galactose from the food they eat. Because they cannot break galactose
down properly, it builds up in their blood. Galactose is found in milk and all foods that contain milk.

WHAT CAUSES GALACTOSEMIA?

In order for the body to use different types of carbohydrates and sugars from the food we eat, special enzymes break
them down into smaller sugar molecules called glucose, which the body uses for fuel.
Lactose, also called milk sugar is the main type of sugar found in milk and milk products. It is made of one molecule
of galactose and one molecule of glucose. Thus, all lactose, and all milk and milk products, contain galactose.
During digestion, lactose is broken down to galactose and glucose. Then galactose is further changed by the body
into glucose so it can be used as energy.
Galactosemia occurs when an enzyme, called galactose-1-phosphate uridyl transferase (GALT) is either missing or
not working properly. This enzymes job is to change galactose into glucose. When the GALT enzyme is missing or
not working properly, galactose cannot be changed to glucose so it builds up in the blood in large amounts. Unless
treated, the excess galactose will affect many parts of the body and, over time, may be life-threatening.
Galactosemia
Galactosemia occurs when babies do not have enough of the GALT enzyme. Babies start showing health effects
within days of feeding on breast milk or milk-containing formulas. Virtually all cases of classic galactosemia can be
detected by newborn screening.

IF GALACTOSEMIA IS NOT TREATED, WHAT PROBLEMS OCCUR?

Excess galactose in the blood affects many parts of the body. Some of the organs that may be affected include the
brain, eyes, liver and kidneys.
Infants with galactosemia usually have diarrhea and vomiting within a few days of drinking milk or formula containing
lactose.
Some of the other early effects of untreated galactosemia include:

Failure to gain weight or grow in length

Poor feeding and poor suck

Lethargy

Irritability

If treatment is not started, other symptoms are likely to follow:

Low blood sugar, called hypoglycemia

Seizures

Enlarged liver that does not work properly

Jaundice (yellow color to the skin or whites of the eyes)

Bleeding

Serious blood infections that could lead to shock and death

Early cataracts which occur in about 10% of children

Some untreated babies have high levels of ammonia, a toxic substance, in their blood. High ammonia levels and
hypoglycemia can both lead to coma and, if not treated, can cause death.
Most untreated children eventually die of liver failure. Surviving babies who remain untreated may have intellectual
disabilities and other damage to the brain and nervous system.
Even with adequate treatment, individuals with galactosemia may develop one or more of the following:

Early cataracts

Mild intellectual disabilities or learning delays

Ataxia (unsteady gait)

Delays in growth

Speech problems and delays

Most girls with galactosemia will have delayed periods or do not get their periods at all. Some women with
galactosemia start menopause early or have premature ovarian failure in which the ovaries stop releasing eggs
earlier than normal menopause.
http://www.newbornscreening.info/Parents/otherdisorders/Galactosemia.html

1. Galactosemia is a disorder caused by enzyme deficiencies that occur in the

galactose metabolic pathway. In an unaffected galactose pathway, the
conversion from galactose to glucose occurs in the liver at a fairly rapid pace. It
begins with the phosphorylation of of galactose utilizing the enzyme
galactokinase, this steps occurs at the expense of an ATP. The phosphorylated
glucose then proceeds to be uridylated using the enzyme galactose 1-phosphate
uridyltransferase. As shown in figure 1, the UDP is derived from a molecule of
UDP-glucose. UDP-galactose is epimerized to UDP-glucose, which then serves
as the donor of UDP to incoming galactose 1-phosphate molecules. This
metabolic pathway results in the production of glucose 1-phosphate, which is
then metabolized to glucose 6-phosphate and entered into the Glycolytic
pathway.

Different
Galactosemia:

types of

Classic and Clinical Variant Galactosemi

Classic and clinical variant galactosemia are rare genetic metabolic disorders. The
patient with classic galactosemia carries deleterious mutations in both copies of their

GALT gene so that their blood shows essentially no detectable residual GALT activity.
The patient with clinical variant galactosemia also carries deleterious mutations in both
copies of their GALT gene, but one or both mutations leave a small amount of residual
GALT activity. In the vast majority of cases, the GALT mutations in classic and clinical
variant galactosemia are inherited so that both parents of an affected child are carriers.
Rare exceptions occur. Patients with classic galactosemia are sometimes described as
having the genetic makeup "G/G." When a person who does not have galactosemia
consumes food containing lactose (e.g., dairy products such as milk, cheese, butter),
their body breaks down the lactose into galactose and glucose, and then further
metabolizes both of these sugars. The human body also is able to make endogenous
galactose. When a person with galactosemia consumes food containing lactose or
galactose they are not able to fully metabolize the galactose, so it can build up in their
cells and tissues. Galactose that is synthesized in the body may also build up. Other
molecules derived from galactose, such as galactose-1-phosphate (Gal-1P), galactitol,
and galactonate, may also build up in the cells and tissues of patients with
galactosemia, especially if they are consuming high levels of dietary lactose or
galactose. Untreated, classic and clinical variant galactosemia are potentially lethal
disorders. If an affected infant continues to drink milk the baby may develop symptoms
that progress in days from jaundice, vomiting, and diarrhea, to liver disease and failure
to thrive, and eventually to E. coli sepsis, which can be fatal.
Diagnosis is made usually within the first weeks of life in follow-up to newborn
screening, which is a blood test from a heel prick offered to all newborns in the United
States and many other countries.
Treatment for classic or clinical variant galactosemia requires the immediate and
strict exclusion of lactose/galactose from the babys diet. This is usually
accomplished by switching the baby from drinking breast milk or a milk-based formula to
drinking a low galactose formula, such as soy or elemental formula. Even with early
diagnosis and careful restriction of lactose/galactose from the diet, however, patients
with classic and clinical variant galactosemia remain at increased risk for long-term
complications that include speech and language, fine and gross motor skill delays and
specific learning or cognitive and behavioral disabilities. Some patients experience
many of these complications; others do not. Primary or premature ovarian insufficiency
is also very common among girls and women with classic and clinical variant
galactosemia. Prenatal diagnosis by genetic or biochemical testing is available.
Duarte Variant Galactosemia
Duarte variant galactosemia, sometimes called just Duarte galactosemia or DG, is
much more common than classic or clinical variant galactosemia in many populations
and also results from mutations in the GALT gene. However, instead of carrying severe
mutations in both copies of their GALT gene, patients with Duarte variant galactosemia
carry one GALT copy with a severe (G) mutation and a second GALT copy that is only
very mildly impaired and that shows a collection of characteristic sequence changes
that classify it as Duarte (also called D or D2). A child with Duarte variant galactosemia

therefore generally has one parent who is a carrier for a severe (G) GALT mutation, and
one parent who is a carrier for the Duarte variant. Patients with Duarte variant
galactosemia usually show about 25% the normal level of GALT activity in red blood
cells. Newborns with Duarte variant galactosemia may not show any symptoms, such
as jaundice, while drinking milk. Experts therefore disagree about whether infants with
Duarte variant galactosemia should be put on a lactose/galactose restricted diet, and no
one knows whether older children or adults with Duarte variant galactosemia are at
increased risk for long-term complications. Reported studies give mixed or inconclusive
results, so that more research is needed to answer the question. If long-term
developmental complications do occur in patients with Duarte variant galactosemia they
are generally believed to be milder than those experienced by patients with classic
galactosemia. Also, girls and women with Duarte variant galactosemia are not believed
to be at risk for premature ovarian insufficiency.
Newborns with Duarte variant galactosemia may or may not be detected by the same
newborn screening test that detects classic or clinical variant galactosemia. Specifically,
some newborn screening protocols are designed to detect Duarte variant galactosemia,
while others do not. Receiving a normal newborn screening result for galactosemia
therefore may not rule out a diagnosis of Duarte variant galactosemia.

What is Galactokinase Deficiency Galactosemia?

Galactokinase deficiency results from inheritance of deleterious mutations in the human
GALK1 gene leading to loss of galactokinase (GALK) enzyme activity. Like patients with
loss of GALT activity, patients missing GALK activity cannot fully metabolize galactose
so that if they consume a diet high in lactose/galactose they will accumulate high levels
of galactose and galactose metabolites including galactitol and presumably galactonate,
though this metabolite is rarely measured. Unlike patients who are missing GALT
activity, patients with galactokinase deficiency do not accumulate high levels of Gal-1P
because GALK is the enzyme that synthesizes Gal-1P.
Galactokinase deficiency is very rare in many populations and is not detected by many
newborn screening programs so that long-term follow-up studies of large numbers of
patients diagnosed with galactokinase deficiency have been difficult to conduct.
Because those patients with galactokinase deficiency studied were ostensibly well as
infants, except for cataracts that self-resolved following dietary galactose restriction,
loss of galactokinase was believed to be relatively benign regardless of diet. That
assumption was challenged in 2011 when Hennermann and colleagues (J Inherit Metab
Dis (2011) 34:399407) reported the identification and follow-up of 18 patients with
galactokinase deficiency detected in Germany by newborn screening between 1991 and
2010. Almost half of these patients were of Romani ancestry, a population believed to

have significantly increased prevalence of GALK deficiency relative to other populations

studied.
.

What is Epimerase Deficiency Galactosemia?

Epimerase deficiency results from inheritance of deleterious mutations in the human
GALE gene leading to partial loss of UDP-galactose 4-epimerase (GALE) enzyme
activity. Like patients with loss of GALT or GALK activity, patients with impaired GALE
activity cannot fully metabolize galactose. However, unlike patients with classic
galactosemia or galactokinase deficiency, all patients with epimerase deficiency
reported to date exhibit only partial loss of enzyme activity. Studies from a fruit fly model
of GALE loss (Sanders et al, Disease Models and Mechanisms 2010, 3(9-10):628-38)
demonstrated that complete loss of GALE activity was lethal early in embryonic
development, perhaps explaining why all live-born patients with epimerase deficiency
show the presence of at least some residual GALE activity.
Patients with impaired GALE activity may be categorized as having one of three forms
of epimerase deficiency: (1) generalized epimerase deficiency which results from
profound but not complete loss of GALE activity, (2) intermediate epimerase deficiency
which results from partial but not profound loss of epimerase activity in multiple tissues,
and (3) peripheral epimerase deficiency which results from loss of epimerase activity
only in some cell types (e.g. red blood cells) but not in others (e.g. lymphoblasts or
liver). In terms of clinical severity, generalized epimerase deficiency is similar to classic
galactosemia, peripheral epimerase deficiency is generally considered benign, and
intermediate epimerase deficiency is of unknown clinical significance. Generalized
epimerase deficiency is extremely rare; other forms of epimerase deficiency may be
much more common, especially in specific populations. Because many newborn
screening programs do not detect epimerase deficiency, the exact prevalence in most
populations remains unknown.

1. Lactose and galactose-free diet:

People with classic galactosemia are encouraged to follow a lactose and galactose-free food plan throughout life.
Lactose or galactose are found in the following foods, all of which must be avoided:

Milk and all dairy products

Processed and pre-packaged foods often contain lactose

Tomato sauces

Some candies

Certain medications tablets, capsules, sweetened liquid drops that contain lactose as a filler

Some fruits and vegetables also contain galactose

Any foods or drugs which contain the ingredients lactulose, casein, caseinate, lactalbumin, curds, whey, or
whey solids.

Your dietitian will help you develop a food plan that allows your child to avoid lactose and galactose while still eating
the right amount of protein, nutrients and energy to keep him or her healthy.
Your childs food plan will depend on many things such as his or her age, weight, general health, and blood test
results. Your dietician will fine-tune your childs diet over time. The special food plan should be continued throughout
life.
2. Special lactose-free formula
Newborns with galactosemia are given a special formula free of lactose. The most common formulas used for babies
with galactosemia are those made with soy protein isolate. Soy milk itself contains galactose and should not be used.
Your metabolic doctor and dietitian will tell you what type of formula is best and how much to use. Some states offer
help with payment, or require private insurance coverage for the formula and other special medical foods.

3. Calcium supplements:
Since children with galactosemia are not eating milk products, calcium intake may be too low. Therefore, children
with galactosemia are often advised to take calcium supplements to ensure they receive enough calcium each day.
Some doctors also advise Vitamin D and Vitamin K supplements in addition to calcium.
4. Monitoring health
Babies and young children with galactosemia usually need regular blood and urine tests. These tests are used to
detect toxic substances made when galactosemia is not in good control. The test results will help your doctors and
dietitian fine-tune the treatment to meet your childs needs.
5. Informing friend, relatives, teachers and child-care providers
It is important for you to tell everyone who helps care for your child that he or she cannot eat or drink milk-containing
foods. A Medic-Alert bracelet that states your childs food restrictions can be helpful. In addition, your doctor may
advise you to carry an emergency treatment letter with steps for your childs care.

Diagnostic test:

Urine sampe:

A galactosemia test is a blood or urine test that checks for the enzymesthat are needed to change
galactose into glucose, a sugar that your body uses for energy.
Blood test
Since galactosemia test is done a baby, a heel stick test would be done and if
the test shows the baby is positive for galactosemia, it would be confirmed on
a blood sample taken from a vein.
http://www.webmd.com/children/galactosemia-test#3