is an inborn carbohydrate metabolic disorder and can be fatal and life-threatening
during the newborn period [1, 2, 3]. Galactosemia is a rare genetic
and an autosomal recessive disorder (meaning a child must inherit one defective
gene from each parent to show the disease), caused by the deficiency of
galactose 1-phosphate uridyltransferase (GALT) [4, 5, 6].
was first described in Germany by von Reuss as cited by George in 1908 and by Göppert in 1917, and first in
the United States by Mason and Turner in 1935 [7, 8, 9]. Kalckar et al.
identified in 1956 that galactosemia is due to defect in galactose metabolism
of galactosemia are galactose diabetes, essential galactosuria, congenital
galactosemia, congenital galactosuria, galactosis, and galactemia .
rate varies in different populations i.e. 1 case per 40,000-60,000 persons (unites
states) 3, 1 case in 70,000 people (UK) but 1 case in 20,000 people
in Ireland. Galactosemia is very
common within the Irish Traveller population. In Asians, this
disorder is less common .
Types of Galactosemia
- Type 1, Classic Galactosemia, the most
common and most severe form. This is due to Galactose-1 phosphate uridyl
transferase (GALT) deficiency.
- Type 2, Deficiency of galactose kinase
- Type 3, Deficiency of
galactose-6-phosphate epimerase (GALE) [3, 11]
Clinical Signs & Symptoms
are prominent signs of this disorder.. Symptoms include Convulsions,
feeding, Poor weight gain, jaundice,
Vomiting. Septicemia (blood infection with E. coli) may be responsible
for these symptoms. Galactosemic infants whom galactose containing diet was not
stopped e.g. breast milk, can develop symptoms within the first few days of
life [1, 3].
LONG TERM COMPLICATIONS
They include premature
ovarian failure and neuropsychiatric features, including cognitive problems,
learning difficulties, behavioral changes, such as withdrawn personality, and
speech difficulties, Cataracts,
retardation, septicemia with E. coli, Tremors and uncontrollable
motor functions, ataxia, decrease in bone mineral density [1, 12, 13, 14, 15].
Normal Galactose Metabolism]
Toxic Metabolites of Galactose
Galactose-1-phosphate are two toxic galactose metabolites. Galactitol is
responsible for the cataracts, and Galactose-1-phosphate induces the
rest of the clinical symptoms. To distinguish galactosemic patients
from normal subjects urine and plasma levels of Galactitol should be
measured. Early diagnosis and strict use of milk free products can help the
patient to live a relatively normal life. However, mild intellectual impairment
may develop, even in people who avoid galactose [1, 17].
What genes are related to
Mutations in the GALE, GALK1, and GALT genes cause
Type of Galactosemia
Classic Galactosemia, type I
Galactosemia type II
Galactosemia type III
These genes provide all the necessary instructions required
for making enzymes that are essential for galactose metabolism. Galactose is
broken down into glucose, another simple sugar and other molecules in the
presence of these enzymes and body can store easily these break down products or
use them for energy. There are two types of mutations in GALT gene: In one type
there is complete elimination of activity of enzyme produced by GALT, this is
called classic Galactosemia and in 2nd type of GALT gene mutation,
there is reduction in activity of enzyme rather than complete elimination and
this is called Duarte Galactosemia variant. The Duarte Galactosemia variant is
caused by N314D. Homozygosity for N314D reduces GALT activity to 50%. People
with the Duarte variant tend to have much milder features of Galactosemia [4,
18, 19, 20].
Location of Galt Gene
The GALT gene is located on
the short (p) arm of chromosome 9
at position 13 (9p13).
More precisely, the GALT gene
is located from base pair 34,646,634 to base pair 34,650,573 on chromosome 9 [6,
19, 21, 22, 23].
Laboratory tests help in diagnosis of this autosomal disorder:
diagnosis by directly measuring the enzyme galactose-1-phosphate
uridyl transferase .
2. A Galt
isoelectric-focusing electrophoresis test for specific molecular diagnosis. The
most common Galt allele in caucasians is the Q188r mutation. The S135l
mutation is common in blacks .
culture for bacterial infection (E. COLI sepsis) .
Measurement of galactose-1-phosphate uridyl transferase activity in RBC [1,
of reducing substances in urine by using tube test 1, 24.
6. Detection of ketones in the urine .
7. Multiplex enzyme assay for galactosemia in erythrocytes using
ultra-performance liquid chromatography-tandem mass spectrometry .
Brain Imaging of Galactosemic Patients
Imaging and proton MR spectroscopy studies showed cerebral and cerebellar
atrophy, multiple small hyper intense lesions in the cerebral white matter on
T2-weighted images [1, 26, 27, 28, 29, 30].
a) Complete elimination of dietary
lactose/galactose, use Soy formula, Meat-based formula or Nutramigen (a protein
hydrolysate formula), anyother lactose-free formula b) supportive therapy with calcium supplements
c) use antibiotic also in case of
treatment can reverse growth failure, Hepatomegaly, formation of cataract and
also reduce the death reports due to septicemia but long term complications can
not be prevented .
toxicity symptoms of this inborn disorder can be prevented in infants by immediate
dietary galactose restriction (do not give mother feed) but it does not ensure
absence of all symptoms and long-term complications routinely occur [4, 33,
34]. Long term complications of Galactosemia are independent of diet .
is a rare genetic autosomal recessive disorder. It is linked with mutations in
GALT, GALE, GALK1 genes. When galactosemic infants feed breast milk, symptoms
start appearing soon after birth. Galactose/ Lactose free diet is pre-requisite
condition for galactosemic persons to pass normal life, though long term
complications can not be prevented because they are independent of diet.
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