Galactosemia screening
why? when? how?
Clinical Children`s Hospital “Louis Turcanu ”
Timisoara, Romania
Galactosemia screening
why?
Galactosemia
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Is a genetic metabolic disease in which
there is a defect in the body's ability to use
the sugar galactose.
People with galactosemia are unable to
metabolize the simple sugar galactose.
Galactose makes up half of the sugar called
lactose that is found in milk. Lactose is a
disaccharide, and is made of two sugars,
galactose and glucose, bound together.
History
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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".
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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.
Galactose
metabolism
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Normally, the body breaks
down lactose into

galactose and then into

glucose (a sugar used for
energy).
People with galactosemia are
missing an enzyme called
GALT , (galactose-1phosphate uridyl
transferase), GALK1 or GALE,
which normally converts
galactose into glucose.
Without this enzymes,
harmful amounts of galactose
build up in the blood.
Lactose metabolism
Galactosemia –
a genetic disease
•Galactosemia is an inherited
disorder.
•Autosomal recessive pattern

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It occurs in
approximately 1 out of
every 60,000 births
among Caucasians.
The rate is different for
other groups.
Three forms of galactosemia

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Galactose-1 phosphate uridyl transferase
deficiency (classic galactosemia, the
most common and most severe form)(GALT) Type I
Deficiency of galactose kinase –
(GALK1)Type II
Deficiency of galactose-6-phosphate –
epimerase (GALE)-Type III
Classic galactosemia – type I
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Galactose-1-phosphate uridyltransferase
defect causes accumulation of galactose
(appears in blood, urine, reduced to galactitol
in lens).
Galactose enters eye, aldose reductase
changes it to galactitol. Galactitol
accumulates in lens and causes infantile
cataracts.
Jaundice, vomiting, poor feeding,
infections
Failure to thrive, hepatomegaly
Speech disabilities, mental retardation
Galactosemia clinical pictures
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The official name of this gene is “galactose-1phosphate uridyltransferase.”

GALT is the gene's official symbol.

Cytogenetic Location: 9p13
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Molecular Location on chromosome 9: base
pairs 34,646,634 to 34,650,573
More precisely, the GALT gene is located from
base pair 34,646,634 to base pair
34,650,573 on chromosome 9.
Genetic variations - GALT
Gene
Symbol
Activity level
Normal
N
100%
Galactosemia - nonfunctioning
Duarte - partially
functioning
g
0%
D
50%
Los Angeles - above
normal functioning gene
LA
125%
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Most commonly seen are Duarte (a
low enzyme producing gene) and Los
Angeles (an enhanced enzyme
producing gene).
These variants and combination of
genes (gN, DN, DD, LAN, LAg, LAD)
do not require treatment or dietary
restriction of galactose.

The Duarte variant is found in 1 in 20
persons.

GALT enzyme (10-25% to 50% activity )
and do not commonly have any symptoms.

The children with Duarte galactosemia
who continue to receive breast milk in the
first year of life might have higher than
normal galactose-1-phosphate levels, but
they do not have any symptoms or health
problems related to the Duarte variant.
Galactokinase – deficiency
or galactosemia Type II
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In 1965, galactokinase deficiency was first identified in
a patient who presented with cataracts and
galactosuria that developed upon drinking milk.
This presentation differed from that of classic
galactosemia in many important aspects; neither
hepatosplenomegaly nor signs of mental retardation
were present.
When the researchers realized that the patient did not
accumulate galactose-1-phosphate despite the
accumulated galactose, the patient's underlying defect
was deduced as the lack of the enzyme mediating 1phosphorylation of galactose.

The official name of this gene is “galactokinase 1.”

GALK1 is the gene's official symbol.
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Cytogenetic Location: 17q24
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Molecular Location on chromosome 17: base pairs
73,754,017 to 73,761,279

More precisely, the GALK1 gene is located from base
pair 73,754,017 to base pair 73,761,279 on
chromosome 17.
Clinical pictures of
Galactosemia Type II
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Mild
Cataract in the
infant
Galactose epimerase deficiency –
galactosemia -Type III
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The official name of this gene is “UDP-galactose-4epimerase.”
More than 20 mutations in the GALE gene have
been identified in people with a form of
galactosemia known as type III or galactose
epimerase deficiency.
Most of these genetic changes alter a single protein
building block (amino acid) in UDP-galactose-4epimerase, which makes the enzyme unstable or
disrupts its usual function.
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Cytogenetic Location: 1p36-p35
Molecular Location on chromosome 1:
base pairs 24,122,088 to 24,127,293
Galactosemia screening
when?
how?
Neo-natal screening
Dry blood spot collect in the 4th
day of life
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From lateral parts of the heel and send it
to the special center from Clinical Children's
Hospital “Louis Turcanu”
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A positive newborn screen test must be
followed by a quantitative erythrocyte
galactose-1-phosphate uridyltransferase
(GALT) analysis
A GALT isoelectric-focusing electrophoresis
test helps distinguish variant forms such as
the Duarte defect.
GALT genotyping may provide a specific
molecular diagnosis
How is treated
galactosemia?

The only way to treat
galactosemia is through
dietary restrictions from the
first days of life

No brest feeding
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Soya- based formula
• The newborn with questionable results on newborn
screening should continue to be treated with soybased formula pending definitive results of
confirmatory testing.
Treatment
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The mainstay of medical care in the
postnatal period is to immediately
discontinue ingestion of lactose-containing
formula.
Totally eliminating galactose is difficult
because it is present in a wide variety of
foods (eg, infant foods, fruits, vegetables)
This ameliorates the acute toxicity
associated with the neonatal period but
does not prevent all long-term
complications.
Galactosemia screening
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Why? If unscreened and untreated,
galactosemia is a life-threatening disorder.
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When? Neonatal period: 4th day
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How? Screening of every neonates, followed
by confirming tests. Thereby, affected infants
are treated before they become ill.
Thank you !