Search our Test Catalog. Specify what to search (name, test code, titles, everywhere) and how to search (begins with, contains)

Unit Code 84367:
Galactosemia Gene Analysis, Known Mutation

Print Friendly View
Print Page Email Page

Useful For

Confirmation of diagnosis of galactosemia in a sibling or other

relative of an individual with documented GALT mutations

 

Predictive testing of potential galactosemia carriers in families of

individuals with documented GALT mutations

Clinical Information

Classic galactosemia is an autosomal recessive disease caused by

mutations in the galactose-1-phosphate uridyltransferase gene (GALT).

The complete or near complete deficiency of the galactose-1-phosphate

uridyl transferase (GALT) enzyme is life threatening. If left untreated,

complications include liver failure, sepsis, mental retardation, and

neonatal death. Galactosemia is treated by a galactose-free diet,

which allows for fast recovery from the acute symptoms and a generally

good prognosis. Despite adequate treatment from an early age, children

with galactosemia remain at increased risk for developmental delays,

speech problems, and abnormalities of motor function. Females with

galactosemia are at increased risk for premature ovarian failure. The

prevalence of classic galactosemia is approximately 1/30,000.

 

Duarte variant galactosemia (compound heterozygosity for the Duarte

mutation, N314D, and a classic mutation) may mimic classic galactosemia

in the biochemical assays used in newborn screening. Typically, Duarte

variant galactosemia has a good prognosis, but is often treated with a low

galactose diet during infancy. The Duarte variant (N314D) is found in 5%

of the general United States population. The silent mutation (L218L),

termed the Los Angeles or D1 Duarte variant, is uncommon and associated

with increased GALT enzyme activity, but the biochemical phenotyping

(by isoelectric focusing) is identical to that of Duarte variant.

 

Newborn screening, which identifies potentially affected individuals by

measuring total galactose (galactose and galactose-1-phosphate) and/

or determining the activity of the GALT enzyme deficiency varies from

state to state. The diagnosis of galactosemia is established by quantitative

measurement of GALT enzyme activity. If enzyme levels are indicative of

carrier status or a diagnosis of galactosemia, molecular testing for common

GALT mutations may be performed. If 1 or both disease-causing mutations

are not detected by targeted mutation analysis and biochemical testing has

confirmed the diagnosis of galactosemia, sequencing of the GALT gene is

available to identify private mutation(s).

 

The GALT gene maps to 9p13 and has 11 exons. More than 180 mutations

have been identified in the GALT gene. Full sequencing of the GALT gene

identifies over 95% of the sequence variants in the coding region and

splice junctions.

 

Several disease-causing mutations are commonly encountered in patients

with classic galactosemia:

-The most frequently observed is the Q188R classic mutation. This

mutation accounts for 60% to 70% of classic galactosemia alleles in

the Caucasian population

-The S135L mutation is the most frequently observed mutation in African

Americans and accounts for approximately 50% of the mutant alleles in

this population

-The K285N mutation is common in those of eastern European descent

and accounts for 25% to 40% of the alleles in this population

-The L195P mutation is observed in 5% to 7% of classic galactosemia

-The Duarte mutation (N314D) is found in 5% of the general United

States population

The above mutations, plus the Los Angles variant, are included in #84360

"Galactosemia Confirmation Test, Blood," the preferred test for the diagnosis of

galactosemia or for follow-up to positive newborn screening results. These mutations

are also included in #84366 "Galactosemia Gene Analysis (6 Mutation Panel)."

Full sequencing of the GALT gene can be useful for the identification of mutations

when 1 or no mutations are found with these tests in an individual with demonstrated

GALT enzyme deficiency. 

Reference Values

An interpretive report will be provided.

Interpretation

An interpretative report will be provided that includes an overview

of the results and their significance, a correlation to available

clinical information, elements of differential diagnosis, and

recommendations for additional testing.

 

For diagnostic purposes, results should be interpreted in the

context of biochemical results.

Cautions

This test should be ordered only when there is a family member

with a mutation previously documented by molecular testing.

 

Not all individuals with galactosemia demonstrate the mutations

included in this panel. The absence of such mutations, therefore,

does not eliminate the possibility of the presence of a mutation

in another region of the gene.

 

Any error in the diagnosis or in the pedigree provided to us,

including false-paternity, could lead to erroneous interpretations

of the results.

 

Medical genetic consultation is available for all DNA diagnosis

cases and is particularly indicated in complex cases or in

situations in which the diagnosis is atypical or uncertain.

Special Instructions and Forms

• Molecular Genetics - Congenital Inherited Diseases Patient Information Sheet 
• Molecular Genetics - Biochemical Disorders Patient Information Sheet 

Clinical Reference

1.   Elsas LJ 2nd, Lai K:  The molecular biology of galactosemia.

      Genet Med 1998 Nov-Dec;1(1):40-48

 

2.   Novelli G, Reichardt JK:  Molecular basis of disorders of human

      galactose metabolism: past, present, and future. Mol Genet

      Metab 2000 Sept-Oct;71(1-2):62-65

Key