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Test Code OLIGU Oligosaccharide Screen, Urine

Useful For

Screening for possible oligosaccharidoses

Disease States

  • Sialidosis
  • Galactosialidosis

Method Name

Matrix-Assisted Laser Desorption Ionization Time-of-Flight Mass Spectrometry (MALDI-TOF MS)

Reporting Name

Oligosaccharide Screen, U

Specimen Type

Urine


Advisory Information


This is the recommended test for the initial workup of a suspected oligosaccharidosis disorder.

 

LYSDU / Lysosomal Storage Disorders Screen, Urine is the recommended screening test for the initial workup of a suspected lysosomal storage disorder.



Necessary Information


1. Patient's age is required.

2. Include family history, clinical condition (asymptomatic or acute episode), diet, and drug therapy information.



Specimen Required


Supplies: Urine Tubes, 10 mL (T068)

Collection Container/Tube: Plastic, 10-mL urine tube (T068)

Specimen Volume: 8 mL

Pediatric Volume: 2 mL

Collection Instructions:

1. Collect a random urine specimen.

2. No preservative.

3. Immediately freeze specimen.


Specimen Minimum Volume

2.5 mL

Specimen Stability Information

Specimen Type Temperature Time
Urine Frozen (preferred) 365 days
  Refrigerated  15 days
  Ambient  7 days

Reject Due To

Hemolysis

NA

Lipemia

NA

Icterus

NA

Other

NA

Clinical Information

The oligosaccharidoses (glycoproteinoses) are a subset of lysosomal storage disorders caused by the deficiency of any one of the lysosomal enzymes involved in the degradation of complex oligosaccharide chains. They are characterized by the abnormal accumulation of incompletely degraded oligosaccharides in cells and tissues and the corresponding increase of related free oligosaccharides in the urine. Clinical diagnosis is difficult due to the similarity of clinical features across disorders and their variability. Clinical features can include bone abnormalities, coarse facial features, corneal cloudiness, organomegaly, muscle weakness, hypotonia, developmental delay, and ataxia. Age of onset ranges from early infancy to adult and can even present prenatally. This is the recommended test for the initial workup of a suspected oligosaccharidosis disorder.

 

The oligosaccharidosis in this subset of lysosomal storage disorders and detected by this assay are alpha-mannosidosis, beta-mannosidosis, aspartylglucosaminuria, fucosidosis, Schindler disease, GM1 gangliosidosis, Sandhoff disease, sialidosis, galactosialidosis, mucolipidoses types II and III, mucopolysaccharidosis IVB (Morquio B), and Pompe disease (see table).

 

LYSDU / Lysosomal Storage Disorders Screen, Urine includes analysis of urine oligosaccharides and is the recommended screening test for the initial workup of a suspected lysosomal storage disorder.

 

Conditions Identifiable By Method

Disorder

Onset

Gene

Enzyme Deficiency

Worldwide Incidence

Alpha-mannosidosis

Prenatal (type III) Infancy (type I)          Juvenile/Adult (type II)

MAN2B1

Alpha-mannosidase

1:500,000

Phenotype: continuum of clinical features ranging from severe and rapidly progressive disease to a milder and more slowly progressive course. Prenatal onset (type III) manifests as prenatal loss or early death from progressive neurodegeneration. Infantile onset (type I) is characterized by rapidly progressive mental retardation, hepatosplenomegaly, and severe dysostosis multiplex. Type II is milder and slower progressing with survival into adulthood.

Beta-mannosidosis

Infancy to juvenile

MANBA

Beta-mannosidase

<100 patients described

 

Phenotype: clinical features vary in severity and may include intellectual disability, respiratory infections, hearing loss, hypotonia, peripheral neuropathy, and behavioral issues.

Aspartylglucosa-minuria

Early childhood

AGA

Aspartylglucosaminidase

1:2,000,000 higher incidence in Finland approx 1:17,000

Phenotype: normal appearing at birth followed by progressive neurodegeneration at 2-4 years, frequent respiratory infections, coarse features, thick calvarium, and osteoporosis. Slowly progressive mental decline into adulthood.

Alpha-fucosidosis

Infancy to early childhood

FUCA1

Alpha-fucosidase

<100 patients described

Phenotype: continuum within a wide spectrum of severity; clinical features include neurodegeneration, coarse facial features, growth delay, recurrent infections, dysostosis multiplex, angiokeratoma, and elevated sweat chloride

Schindler disease

Infancy (type I)Early childhood (type III)

Adult (type II)

NAGA

Alpha-N-Acetyl-galactosaminidase

<30 patients described

Phenotype: continuum of clinical features ranging from severe and rapidly progressive disease to a milder and more slowly progressive course; infantile onset (type I) is characterized by rapidly progressive neurodegeneration. Type II is adult onset characterized by angiokeratoma and mild cognitive impairment, and type III is an intermediate and variable form ranging from seizures and psychomotor delay to milder autistic features.

GM1 gangliosidosis

Infancy (type I)

Late infantile/juvenile (type II)

Adult (type III)

GLB1

Beta-galactosidase (Beta-Gal)

1:200,000

Phenotype: continuum of clinical features ranging from severe and rapidly progressive disease to a milder and more slowly progressive course; infantile onset (type I) is characterized by early developmental delay/arrest followed by progressive neurodegeneration, skeletal dysplasia, facial coarseness, hepatosplenomegaly, and macular cherry red spot. Later onset forms (types II and III) are milder and observed as progressive neurologic disease and vertebral dysplasia. Adult onset presents mainly with dystonia.

GM2 gangliosidosis variant 0

(Sandhoff disease)

Early infancy to juvenile or adult

HEXB

Beta-hexosaminidase A and B

1:400,000

Phenotype: infantile onset is characterized by rapidly progressive neurodegeneration, exaggerated startle reflex, "cherry red spot". Milder later-adult onset forms of the disease exist presenting with neurological problems such as ataxia, dystonia, spinal-cerebellar degeneration, and behavior changes.

Sialidosis (ML I)

Early adulthood (type I)

Earlier for congenital, infantile, and juvenile forms (type II)

NEU1

Alpha-neuraminidase (Neu)

<30 patients described

Phenotype: continuum of clinical features ranging from severe disease (type II) to a milder and more slowly progressive course (type I). Clinical features range from early developmental delay, coarse facial features, short stature, dysostosis multiplex, and hepatosplenomegaly to late onset cherry-red spot myoclonus syndrome. Seizures, hyperreflexia, and ataxia have been reported in more than 50% of later onset patients. A congenital form of the disease has been reported in which patients present with fetal hydrops or neonatal ascites.

Galactosialidosis

Early infancy, late infancy or early adult

CTSA

Cathepsin A causing secondary deficiencies in Beta-Gal and Neu

<30 patients described

Phenotype: continuum of clinical features ranging from severe and rapidly progressive disease to a milder and more slowly progressive course; clinical features of the early infantile type include fetal hydrops, edema, ascites, visceromegaly, dysostosis multiplex, coarse facies, and cherry red spot. The majority of patients have milder presentations, which include ataxia, myoclonus, angiokeratoma, cognitive and neurologic decline.

Mucolipidosis II-alpha/-beta (I-cell)

Mucolipidosis III-alpha/-beta and III-gamma (pseudo-Hurler Polydystrophy)

Early infancy

 

Early childhood, may live well into adulthood 

GNPTAB(alpha/beta)

GNPTG (gamma)

N-acetylglucosaminyl-1-phosphotransferase deficiency causing secondary intracellular deficiency of multiple enzyme activities

1:300,000

Phenotype: I-cell resembles Hurler with short stature and skeletal anomalies, but presents earlier, is more severe, and can include cardiomyopathy and coronary artery disease. Pseudo-Hurler polydystrophy is milder and later presenting.

Mucopoly-saccharidosis IVB (Morquio B)

Infancy to adult

GLB1

Beta-galactosidase
(Beta-Gal)

1:75,000 N. Ireland

1:640,000 W. Australia

Phenotype: progressive condition that largely affects the skeletal system. Features include short-trunk dwarfism, skeletal (spondyloepiphyseal) dysplasia, fine corneal deposits, and preservation of intelligence.

Pompe disease (Glycogen storage disease type II)

Early infancy

Late onset (childhood-adult)

GAA

Alpha-glucosidase

1:40,000

Phenotype: infantile onset is characterized by prominent cardiomegaly, hepatomegaly, hypotonia, and weakness. Later onset forms present with proximal muscle weakness and respiratory insufficiency.

 

Reference Values

An interpretive report will be provided.

Interpretation

This is a screening test; not all oligosaccharidoses are detected. The resulting excretion profile may be characteristic of a specific disorder; however, abnormal results require confirmation by enzyme assay or molecular genetic testing.

 

When abnormal results are detected with characteristic patterns, a detailed interpretation is given, including an overview of results and significance, a correlation to available clinical information, elements of differential diagnosis, recommendations for additional confirmatory studies (enzyme assay, molecular genetic analysis).

Cautions

This test may give false-negative results, especially in older patients with mild clinical presentations.

 

This test may give false-positive Pompe disease results, especially in pediatric patients on infant formula.

 

Enzyme or molecular analysis is required to confirm suspected diagnosis.

Method Description

Urine samples are extracted using Oasis HLB and carbograph columns and lyophilized overnight. Oligosaccharides are permethylated, which replaces all hydroxy groups (-OH) with methoxy groups (-O-CH3) and esterifies carboxyl groups (-COOH) to (-COOCH3). After permethylation, the tubes are centrifuged and the supernatant taken off of the sodium hydroxide pellet. The supernatant is quenched with water, neutralized with acetic acid, extracted onto an Oasis HLB column, eluted with 30:70 AcN:water and again lyophilized overnight. Specimens are resuspended in 50:50 methanol:water, mixed 1:1 with a matrix solution containing 2,5-dihydroxybenzoic acid, spotted onto a MALDI plate and allowed to air dry. The plate is then analyzed using a MALDI TOF/TOF 5800 Analyzer.(Xia B, Asif G, Arthur L, et al: Oligosaccharide analysis in urine by MALDI-TOF mass spectrometry for the diagnosis of lysosomal storage diseases. Clin Chem 2013 Sep;59(9):1357-1368)

Day(s) and Time(s) Performed

Varies

Analytic Time

8 days

Specimen Retention Time

1 month

Performing Laboratory

Mayo Medical Laboratories in Rochester

Test Classification

This test was developed and its performance characteristics determined by Mayo Clinic in a manner consistent with CLIA requirements. This test has not been cleared or approved by the U.S. Food and Drug Administration.

CPT Code Information

84377

LOINC Code Information

Test ID Test Order Name Order LOINC Value
OLIGU Oligosaccharide Screen, U 49284-3

 

Result ID Test Result Name Result LOINC Value
64889 Oligosaccharide Screen, U 49284-3

Testing Algorithm

See Newborn Screen Follow-up for Pompe Disease in Special Instructions.

 

For more information, see Newborn Screening Act Sheet Pompe Disease: Decreased Acid Alpha-Glucosidase in Special Instructions.

Forms

Biochemical Genetics Patient Information (T602) in Special Instructions