Galactosemia is a rare genetic metabolic disorder caused by a deficiency of the enzyme galactose-1-phosphate uridyltransferase, which is necessary for galactose metabolism. There are three main types depending on the specific enzyme deficiency. It is inherited in an autosomal recessive pattern and causes an inability to properly break down and use the sugar galactose. If left untreated, it can cause serious issues such as liver damage, cataracts, intellectual disabilities and more. Treatment involves a strict lifelong galactose-restricted diet.

1. GALACTOSEMIA
BY:
GOKULABALAJI.V
II MSC BIOCHEMISTRY &
MOLECULAR BIOLOGY
PONDICHERRY UNIVERSITY

2. WHAT IS GALACTOSEMIA?
It is a rare genetic metabolic disorder that affects
how the body processes a simple sugar called
galactose.
Inability of the body to use galactose to produce
energy.

3. The chromosome is affected is 9
The amino acid is
changed within the
chromosome.

6. 3 inborn errors related to galactose
metabolism:
1. Galactose-1-phosphate uridyltransferase
deficiency
2. Galactokinase deficiency
3. Uridine diphosphate-galactose 4-epimerase
deficiency

7. TYPES:
Type OMIM Gene Locu
s
Enzyme Name
Type 1 230400 GALT 9P13 Galactose1- phosphat
uridyl transferase
Classic galactosemia
Type 2 230200 GALK1 17q24 galactokinase Galactokinase
deficiency
Type 3 230350 GALE 1p36-
p35
UDP galactose
epimerase
UDP-Galactose- 4-
epimerase deficiency
Galactose is converted into glucose by the action of three enzymes,
known as the Leloir pathway:

8. Gene location:
GALE
GALT
GALK1
GALE
GALT
GALK1

9. Frequency
Classic galactosemia occurs
in 1 in 30,000 to 60,000
newborns. Galactosemia
type II and type III are less
common; type II probably
affects fewer than 1 in
100,000 newborns and type
III appears to be very rare.

10. Mode of inheritance
To have an autosomal recessive
disorder, you inherit two
mutated genes, one from each
parent. These disorders are
usually passed on by two
carriers. Their health is rarely
affected, but they have one
mutated gene (recessive gene)
and one normal gene (dominant
gene) for the condition. Two
carriers have a 25 percent
chance of having an unaffected

11. Galactosemia is due to deficiency of the enzyme galactose
1-phosphate uridyltransferase.
It is a rare congenital disease in infants, inherited as autosomal
recessive disorder.
Mutation in the GALT gene located on chromosome 9 is
responsible for this disorder.
1. Galactose metabolism is impaired leading to increased galactose
levels in blood (galactosemia) and urine (galactosuria).
2. Accumulated galactose is diverted for production of galactitol by
the enzyme aldol reductase. Galactitol has been implicated in the
development of cataract.

12. 3. The accumulation of galactose 1-phosphate and
galactitol in various tissues like liver, nervous tissue,
lens and kidney leads to impairment in their function.
4. The accumulation of galactose 1-phosphate in liver
results in the depletion of inorganic phosphate for
other metabolic functions.
CLINICAL SYMPTOMS:
• Weight loss (in infants)
• Hepatosplenogamy
• Jaundice
• Mental retardation
• Severe cases : cataract,
amino aciduria and albuminuria.

13. Diagnosis
Prenatal Testing A doctor can determine during
a woman’s pregnancy whether her baby has
galactosemia through:
a. amniocentesis . This procedure involves using
a needle to withdraw a sample of amniotic
fluid from the womb, and then examining the
cells.
b. chronic villus sampling or CVS
c. NewBorn Screening -Babies are tested for
Galactosemia at birth using a tiny blood
sample taken from the baby’s heel, the test for
low level of the GALT enzyme.

14. • Defect in the enzyme galactokinase responsible for
phosphorylation of galactose.
• Mutation in GALK1 gene.
• Galactose is shunted to the formation of galactitol.
• Cataract development at a very early age, sometimes
within an year after birth.
• Treatment involves removal of galactose and lactose
from the diet.

15. • Extremely rare.
• Mutations in GALE gene is responsible.
• Symptoms vary from mild to severe and can include
cataracts, delayed growth and development,
intellectual disability, liver disease and kidney
problems.

16. Treatment
• No treatment or cannot be cure but with
maturation most children develop another
enzyme capable of metabolizing galactose.
• As a consequence, they are able to tolerate
galactose as they mature.
• Dietary restriction, avoid food and drinks
containing galactose like milk, cheese,
legumes (dried beans), fermented soy
products, organ meat and hydrolyzed proteins.

17. Recent trials
1. Applied Therapeutics Inc.
(Nasdaq:APLT), a clinical-stage
biopharmaceutical company
developing a pipeline of novel
drug candidates against
validated molecular targets in
indications of high unmet
medical need, June 24, 2019
announced the initiation of a
Phase 1/2 study of AT-007 in
Galactosemia
2. arginine is an amino acid that is
therapeutically widely used with
no side effects described, we
propose to use it in a pilot-clinical
study. We aim to evaluate the
effects of arginine in classic
galactosemia patients, in order to
determine its potential
therapeutic role in this disease.

18. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5391384/

19. https://www.globenewswire.com/news-
release/2019/06/24/1872873/0/en/Applied-
Therapeutics-Announces-Initiation-of-Phase-
1-2-Study-of-AT-007-in-Galactosemia.html

20. • http://www.galactosemia.org/understanding-
galactosemia/
• https://www.semanticscholar.org/paper/Galactosem
ia-%3A-A-Genetic-Disease-of-Leloir-Pathway-Ali-
Khan/dac8ff14d4f2662b4e8c0b5377aeca0ba9df15b
4
• https://rarediseases.info.nih.gov/diseases/2424/gala
ctosemia