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Galactosemia denotes the elevated level of galactose in the blood
and is found in three distinct inborn errors of galactose metabolism (Chapter 154, Fig. 154-1) in one of the following
enzymes: galactose-1-phosphate uridyl transferase, galactokinase,
and uridine diphosphate galactose-4-epimerase. The term galactosemia,
although adequate for the deficiencies for any of these three disorders, generally
designates the transferase deficiency, which is by far the most
prevalent and is called classical galactosemia.1
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Classic galactosemia due to a complete galactose-1-phosphate
uridyl transferase deficiency is a serious disease, with an incidence
of approximately 1 in 60,000. Symptoms typically appear by the second
half of the first week of life. The newborn receives high amounts
of lactose (up to 40% in breast milk and certain formulas),
which consists of equal parts of glucose and galactose. Without
the transferase, the infant is unable to metabolize galactose-1-phosphate (see
Chapter 154, Fig. 154-1), the accumulation of
which results in injury to parenchymal cells of the kidney, liver,
and brain.
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Clinical Presentation and
Laboratory Findings
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The diagnosis of uridyl transferase deficiency should be considered
in newborns, older infants, or children with any of these clinical
manifestations: jaundice, hepatomegaly, vomiting, hypoglycemia,
convulsions, lethargy, irritability, feeding difficulties, poor
weight gain, aminoaciduria, nuclear cataracts, vitreous hemorrhage, hepatic
cirrhosis, ascites, splenomegaly, or mental retardation. Patients
with galactosemia are at increased risk for Escherichia
coli neonatal sepsis; the onset of sepsis often precedes
the diagnosis of galactosemia. Pseudotumor cerebri may occur and
may cause a bulging fontanel.
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When the diagnosis is not made at birth, damage to the liver
(cirrhosis) and brain (mental retardation) becomes increasingly
severe and irreversible. Symptoms are milder and improve when milk
is temporarily withdrawn and replaced by lactose-free nutrition.
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Partial transferase deficiency due to Duarte variant is generally
asymptomatic. It is more frequent than classic galactosemia and
is often diagnosed in mass newborn screening because of moderately
elevated blood galactose or low transferase activity.
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Transferase deficiency galactosemia (OMIM 230400) is inherited
as an autosomal recessive disorder. There are several enzymatic
variants of galactosemia. Duarte variant is the most common and
has a carrier frequency of 12% in the general population.
Individuals with Duarte variant homozygote have diminished red cell
enzyme activity (50% of normal) but usually no clinical
manifestations. Individuals with Duarte galactosemia (D/G)
compound heterozygosity have 25% of the enzyme activity,
and galactose-1-phosphate levels are often elevated. These children
are usually asymptomatic, but most physicians restrict lactose intake
if the erythrocyte galactose-1-phosphate levels are elevated. Some
African American patients have milder symptoms despite absence of
measurable transferase activity in erythrocytes; these patients
retain 10% enzyme activity in liver and intestinal mucosa, while
most white patients have no detectable activity in any of these
tissues. The gene for galactose-1-phosphate uridyl transferase is
located on chromosome 9p13. In African Americans, 48% of
alleles ...