GALACTOSEMIA

Group 5 - 1B1
Coronel • Cuenco • Culaba • Danoli • Daro
Learning Objectives
Discuss the metabolic reactions that galactose undergo after
absorption.
Define Galactosemia.
Differentiate the different types of galactosemia as to the
enzymes that are deficient, clinical manifestations.
Explain the different laboratory procedures that can be done
to diagnose galactosemia.
Discuss the treatment of galactosemia.
Galactose
- a monosaccharide
- an aldohexose
- a C-4 epimer of glucose
Galactose
- derived from the intestinal hydrolysis of the
disaccharide, lactose
Galactose
Metabolism
1
Metabolic reaction that
galactose undergoes as it is
converted to glucose
 Phosphorylation of galactose
1 to galactose 1-phosphate
Enzyme: Galactokinase
- phosphorylation of galactose to galactose 1-phosphate by
galactokinase, using ATP as phosphate donor
- galactokinase attaches phosphate to the hydroxyl group
on carbon-1 to form Gal 1-P
 Galactose 1-phosphate and UDP-glucose
2 react to form UDP-galactose and
glucose-1-phosphate
Enzyme: Galactose-1-phosphate uridyltransferase

- galactose 1-phosphate reacts with UDPGlc

- galactose-1-phosphate uridyltransferase catalyzes an
exchange between the two to form uridine diphosphate
galactose (UDPGal) and glucose-1-phosphate
 Conversion of UDPGal to
3 UDPGlc
Enzyme: UDP-galactose 4-epimerase
- The galactose moiety of UDP-galactose is epimerized to glucose.
The configuration of the hydroxyl group at carbon 4 is inverted by
UDP-galactose 4-epimerase.
- UDP-glucose is not consumed in the conversion of galactose into
glucose, because it is regenerated from UDP-galactose by the
epimerase
 Conversion of UDPGal to
3 UDPGlc
Enzyme: UDP-galactose 4-epimerase
- The conversion of UDP-glucose into UDP-galactose is essential
for the synthesis of galactosyl residues in complex
polysaccharides and glycoproteins if the amount of galactose in
the diet is inadequate to meet these needs.
- UDP-GLc is present in only micromolar concentrations in cells so
that its availability of galactose metabolism would be quickly
exhausted where it not for the presence of UDP-Gal-4-epimerase.
 Conversion of Glucose-1-Phosphate
4 to Glucose-6-Phosphate
Enzyme: Phosphoglucomutase
- glucose 1-phosphate is converted to glucose 6-phosphate
by phosphoglucomutase
Summary of conversion of
Galactose to Glucose
2
Metabolic reaction that
galactose undergoes as it
becomes part of lactose and
other galactolipids
- UDPGal condenses with glucose which is catalyzed by enzyme
lactose synthase which will yield to lactose.

- Galactose is required in the body not only for the formation of

lactose in lactation, but also as a constituent of glycolipids,
proteoglycans, and glycoproteins.
3
Metabolic reaction that
galactose undergoes as it is
oxidized as source of energy
- Glycolysis is the conversion of glucose to pyruvate. It has an
energy–investment phase and energy–generation phase with a
net of two molecules of ATP.
Galactosemia
- rare inherited condition
- “galactose in the blood”
- People who have this disorder have difficulty when digesting
dairy products or food that contain milk (like in many baby
formulas)
Galactosemia
- occurs due to a deficiency of Galactose-1-phosphate: uridyl
transferase (GALT), galactokinase (GALK) or UDP-galactose-4
epimerase (GALE)
 Types of Galactosemia

TYPE I TYPE II TYPE III

Classic Galactokinase Galactose
Galactosemia Deficiency Epimerase
Deficiency
TYPE I: Classic Galactosemia
● most common and most severe form of
galactosemia
● occurs in 1 in every 30 000 births
● GALT deficiency/Galactose-1-phosphate
uridyltransferase deficiency
TYPE I: Classic Galactosemia
● caused by mutations in the GALT gene
○ located on the short arm of chromosome 9 at
position 13.3
○ GALT gene provides instructions for making
an enzyme called galactose-1-phosphate
uridylyltransferase (GALT)
TYPE I: Classic Galactosemia
● GALT deficiency causes
○ galactosemia and galactosuria
○ vomiting
○ diarrhea
○ jaundice
● accumulation of galactose 1-phosphate and
galactitol in nerve, lens, liver, and kidneys tissue
causes
○ liver damage
○ severe mental retardation
○ cataracts
 TYPE II: Galactokinase
Deficiency
● GALK deficiency/Galactokinase deficiency
● occurs in less than 1 out of every 100,000 births
● caused by mutations in the GALK1 gene
○ located on the long arm of chromosome 17 at
position 25.1
 TYPE II: Galactokinase
Deficiency
● GALK deficiency causes
○ galactosemia
○ galactosuria
○ cataracts
● Children with untreated GALK usually develop vision
trouble during early childhood. This is why early
screening and identification is so important.
 TYPE III: Galactose
Epimerase Deficiency
● GALE deficiency/UDP-galactose-4 epimerase
deficiency
● characterized by a deficiency of the enzyme
UDP-galactose-4-epimerase
● occurs most often in African American
populations with 1 out of every 6 700 newborns
diagnosed with GALE
● less common in other ethnic groups with 1 out of
every 70 000 European individuals
 TYPE III: Galactose
Epimerase Deficiency
● extremely rare
● caused by mutations in the GALE gene
○ located on the short arm of chromosome 1 at
position 36.11
 TYPE III: Galactose
Epimerase Deficiency
● GALE deficiency causes
○ poor feeding
○ vomiting
○ weight loss
○ jaundice
○ hepatomegaly
○ liver dysfunction
○ cataracts
 Summary
TYPE ENZYME DEFICIENT CLINICAL MOLECULAR
MANIFESTATION BASIS
Classic Galactose-1-phosphate Galactosemia GALT gene
Galactosemia uridyltransferase Galactosuria mutation
Jaundice
Liver damage
Severe mental retardation
Cataracts
Vomiting
Hypoglycemia

Galactokinase Galactokinase Galactosemia GALK1 gene

Deficiency Galactosuria mutation
Cataracts

Epimerase Uridine Poor feeding GALE gene

Deficiency diphosphate-galactose Vomiting mutation
Weight loss
4-epimerase
Jaundice
Hepatomegaly
Liver dysfunction
Cataracts
DIAGNOSIS EXAMINATION
● Infants are routinely screened for galactosemia and
diagnosis is made while the person is an infant
● May have diagnostic delays
● Galactosemia is first detected through the Newborn
Screening (NBS)
● If the family has a history of galactosemia, doctors can test
prior to birth by taking a sample of fluid from around the
fetus or from the placenta
● Untreated infants may die within the first two weeks of life
DIAGNOSIS EXAMINATION
Newborn Screening Test (NBS
● an accurate detection for galactosemia
● Determines the level of galactose-1-phosphate (GAL-1-P)
enzyme in the blood
● Used to diagnose
Classic Galactosemia
DIAGNOSIS EXAMINATION
Fluorometric Assay
● Primary screening for NBS
● Determines the level of galactose in the blood specimen
● Positive result: High level
- must take the succeeding test
Beutler Assay
● Secondary screening
● Measures the GALT enzyme activity
● Infants who have not ingested lactose and has low level of
GAL-1-P, must still take the Beutler Assay
DIAGNOSIS EXAMINATION
● False negative false positive are common
● Presumptive positive results: no GALT activity detected or
excessively elevated galactose level -> immediate
follow-up
● Classical Galactosemia: GAL-1-P is elevated in red blood
cells and GALT enzyme is reduced
DIAGNOSIS EXAMINATION
Genetic Testing
● Prenatal Diagnosis- possible but rare
● testing performed on a Chronic Villus Sampling or amniotic
fluid (amniocentesis) sample
● GALT Assay- distinguishes well the GALT activity in
cultured amniotic fluid
● evaluates the likeliness that the disorder is present in the
fetus
● When employed after birth: used to determine the exact
type of GALT gene mutation in an infant who has a
confirmed GALT enzyme deficiency
DIAGNOSIS EXAMINATION
Genetic Testing
TREATMENT
Long term:
1. Minimize or prevent dietary galactose intake
● galactose should be excluded as soon as galactosemia
is suspected
● breastfeeding and cow’s milk formulas must be
stopped
2. Initial care needed for other symptoms
● Jaundice, sepsis, abnormalities of the liver, kidneys,
central nervous system
● Supportive therapy: intravenous hydration, v.
antibiotics, treatment of coagulopathy
TREATMENT
For GALK Deficiency:
1. Cataracts may be reversible
2. Galactose-free diet must be started in early infancy

For Epimerase Deficiency:

1. No specific treatment required
2. Restriction of dietary galactose
CASE REPORT
Patient: newborn baby, appeared normal at birth

Diagnosis: Classic Galactosemia

Signs and Symptoms:

● Vomiting after breastfeeding
● Diarrhea
● Loss of appetite
● Jaundice
● Hepatomegaly
● Cataract
CASE REPORT
Laboratory Procedure:
● Measurement of glucose concentration in the blood
● Colorimetric method

Findings:
● Low blood glucose concentration
● High sugar (galactose) concentration in blood and urine
CASE REPORT
Treatment:
● Changed the diet of the baby -> removed lactose
● Replaced milk with an infant formula which contained
sucrose rather than lactose

Results:
● Vomiting stopped
● Diarrhea stopped
● Hepatic function gradually improved
Thank you