2. Introduction
Galactose is converted to glucose to be metabolized.
Generally speaking 3 enzymes take part in this process:
GALT(galactose-1-phosphate-uridylyltransferase)
GALK(galactokinase)
GALE(UDP-Gal epimerase)
Galactosemia is a hereditary disease caused by lack of a liver enzyme/s
required to digest galactose. This shouldn’t be confused with Lactose intolerance
which only results in the inability to break down lactose due to Lactase
deficiency.
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5. History
Galactosemia was first discovered in 1908 by the
physician Von Ruess.
Publication entitled, "Sugar Excretion in Infancy,"
reported on a breast-fed infant with failure to
thrive, enlargement of the liver and spleen, and
"galactosuria".
6. Cont….
In 1917, Goppert reported an infant with poor growth, lactose exposure, and
hypergalactosuria
The first comprehensive description of the variant form of hereditary
galactosemia was in 1935 by Mason and Turner of an African-American
infant. It was also the first report of a patient with any form of galactosemia
due to GALT deficiency in the American literature. This patient had not been
placed on a lactose-restricted diet until 10 months of age.
7. Aetiology
Galactosemia is an autosomal recessive disorder, meaning the allele must be
found in a homozygous form for it to be expressed. Therefore it is usually
characterized by:
does not usually affect the parents, but siblings may show the disease
In many cases, enzyme proteins are affected by the mutation.
recurrence risk is 25% for each birth(If parents are hetrozygote)
In heterozygotes, equal amounts of normal and defective enzyme are
synthesized. ("margin of safety")
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9. Types and Pathophysiology
There are 3 types based on which enzyme is deactivated:
Type I (Classic)-(G/G)
Both copies of GALT gene(p-arm of chrom 9) are deleterious, no
GALT activity
Most common and severe
Build up of galactose, Gal-1-P, galacitol, galactonate
Mostly inherited, with both parents being carriers
May be lethal if untreated
Lethargy, FTT, liver damage, cataract(tonicity),speech difficulties,
intellectual disability, sepsis and shock.
10. Gene Symbol Activity level
Normal N 100%
Galactosemia - non-
functioning
G 0%
Duarte - partially
functioning
D 50%
Los Angeles - above
normal functioning gene
LA 125%
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13. Cont…
Type II
Deleterious mutation in the GALK1 gene(q-arm of chrom 17)
Total loss of GALK activity
Lower levels of Gal-1-P
Presence of Galactosuria
Fewer medical problems are seen
Some infants develop cataracts
14. Cont….
Type III
Deleterious mutation of the GALE gene(p-arm of chrom 1)
leads to partial loss of the enzymatic activity of GALE
The signs and symptoms of galactosemia type III vary from mild to severe
and can include cataracts, delayed growth and development, intellectual
disability, liver disease, and kidney problems.
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16. Epidemiology
Studies show:
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
Type III appears to be very rare.
1 in 7,500 births - some form of galactosemia
It is estimated that 1 in every 40 people may be a carrier
The Duarte variant is found in 1 in 20 persons.
17. Symptoms
Can manifest in the first few days of life if there is consumption of galactose
Symptoms are:
Convulsions
Irritability
Lethargy
FTT
Jaundice
Vomiting
Poor feeding
18. Exams and Tests
These include:
Blood culture for bacterial infections (E.coli sepsis)
Enzyme activity in red blood cells
Ketones in urine
Prenatal diagnosis by directly measuring the enzyme galactose-1-
phosphate uridylyl transferase
"Reducing substances" in the infant's urine, and normal or low blood
sugar while the infant is being fed breast milk or a formula containing
lactose
19. Prognosis
People who are diagnosed early and strictly avoid milk
products can live a relatively normal life. However, mild
mental impairment may develop, even in people who
avoid galactose.
20. Treatment and prevention
People with this condition must avoid all milk, dairy products, and other foods
that contain galactose, for life. Instead infants can be fed:
Soy formula
Another lactose-free formula
Meat-based formula or Nutramigen (a protein hydrolysate formula)
21. Cont….
helpful for an individual to know their family history
Genetic counseling must be given to couples who have a
family history of galactosemia
If the newborn shows possible galactosemia , they must
prevent the newborn from consuming galactose-laden
products