2. Pathology of inherited diseases
Lack of glucose for the metabolism of brain, muscle,
liver, or kidney (in circumstances in which ketone
bodies cannot be used).
Inability to break down glucose to pyruvate.
Inability to oxidize pyruvate fully in the Krebs cycle.
3. 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.
Galactosemia type II results from mutations in the
GALK1 gene, while mutations in the GALE gene
underlie galactosemia type III. Like the enzyme
produced from the GALT gene, the enzymes made
from the GALK1 and GALE genes play important
roles in processing galactose.
The chromosome 9 is affected.
4.
5.
6. 3 inborn errors related to galactose metabolism:
1. Galactose-1-phosphate uridyltransferase deficiency.
2. Galactokinase deficiency.
3. Uridine diphosphate-galactose 4-epimerase deficiency.
• Galactose metabolism is impaired leading to increased
galactose levels in blood (galactosemia) and urine
(galactosuria).
• Accumulated galactose is diverted for production of
galactitol by the enzyme aldol reductase. Galactitol has been
implicated in the development of cataract.
• The accumulation of galactose 1-phosphate and galactitol in
various tissues like liver, nervous tissue, lens and kidney
leads to impairment in their function.
• The accumulation of galactose 1-phosphate in liver results
in the depletion of inorganic phosphate for other metabolic
functions.
7. 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.
CLINICAL SYMPTOMS:
Weight loss (in infants)
Hepatosplenogamy
Jaundice
Mental retardation
Severe cases : cataract, amino aciduria and
albuminuria000 newborns and type III appears to be very
rare.
8. Diagnosis
Prenatal Testing A doctor can determine during a
woman’s pregnancy whether her baby has
galactosemia through:
Amniocentesis . This procedure involves using a
needle to withdraw a sample of amniotic fluid from
the womb, and then examining the cells.
Chronic villus sampling or CVS.
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.
9. 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.
10. Recent Trials
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.
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.
