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Test ID MPSBS Mucopolysaccharidosis, Blood Spot

Useful For

Quantification of heparan sulfate, dermatan sulfate, and keratan sulfate in dried blood spots can support the biochemical diagnosis of one of the mucopolysaccharidoses types I, II, III, IV, or VI.

Method Name

Liquid Chromatography-Tandem Mass Spectrometry (LC-MS/MS) 

Reporting Name

Mucopolysaccharidosis, BS

Specimen Type

Whole blood


Specimen Required


Patient Preparation: Do not administer low-molecular-weight heparin prior to collection

Supplies: Card-Blood Spot Collection (Filter Paper) (T493)

Collection Container:

Preferred: Card-Blood Spot Collection (Filter Paper) (T493)

Acceptable: Whatman Protein Saver 903 paper, Ahlstrom 226 filter paper, Munktell filter paper, local newborn screening card, postmortem screening card, or blood collected in tubes containing ACD or EDTA and dried on filter paper

Specimen Volume: 2 dried blood spots

Collection Instructions

1. Completely fill at least 2 circles on the filter paper card (approximately 100 microliters blood per circle).

2. Let blood dry on filter paper at room temperature in a horizontal position for 3 or more hours.

3. Do not expose specimen to heat or direct sunlight.

4. Do not stack wet specimens.

5. Keep specimen dry.

Additional Information:

1. For collection instructions in Spanish, see Blood Spot Collection Card-Spanish Instructions (T777) in Special Instructions.

2. For collection instructions in Chinese, see Blood Spot Collection Card-Chinese Instructions (T800) in Special Instructions.


Specimen Minimum Volume

See Specimen Required

Specimen Stability Information

Specimen Type Temperature Time
Whole blood Ambient (preferred) 100 days
  Frozen  100 days
  Refrigerated  100 days

Clinical Information

The mucopolysaccharidoses (MPS) are a group of disorders caused by a deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans: GAGs, also called mucopolysaccharides). Undegraded or partially degraded GAGs are stored in lysosomes and excreted in the urine. Accumulation of GAGs in lysosomes interferes with normal functioning of cells, tissues, and organs resulting in the clinical features observed in MPS disorders. Depending on the extent of the enzyme deficiency and type of accumulating storage material, MPS patients may present with a variety of clinical findings that can include coarse facial features, cardiac abnormalities, organomegaly, intellectual disabilities, short stature and skeletal abnormalities.

 

MPS I is an autosomal recessive disorder caused by reduced or absent activity of the enzyme alpha-L-iduronidase due to mutations in the IDUA gene. This enzyme deficiency results in a wide range of clinical phenotypes that are further categorized as MPS IH (Hurler syndrome), MPS IS (Scheie syndrome), and MPS IH/S (Hurler-Scheie syndrome), and which cannot be distinguished via biochemical methods. Clinically, they are also referred to as MPS I and attenuated MPS I. MPS IH is the most severe and has an early onset consisting of skeletal deformities, coarse facial features, hepatosplenomegaly, macrocephaly, cardiomyopathy, hearing loss, macroglossia, and respiratory tract infections. Developmental delay is noticed as early as 12 months, and without treatment, death usually occurs before 10 years of age. MPS IH/S has an intermediate clinical presentation characterized by progressive skeletal symptoms called dysostosis multiplex. Individuals typically have little or no intellectual dysfunction. Corneal clouding, joint stiffness, deafness, and valvular heart disease can develop by early to mid-teens. Survival into adulthood is common. Comparatively, MPS IS presents with the mildest phenotype. The onset occurs after 5 years of age. It is characterized by normal intelligence and stature; however, affected individuals do experience joint involvement, visual impairment, and obstructive airway disease. The incidence of MPS I is approximately 1 in 100,000 live births. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy.

 

MPS II, Hunter syndrome is an X-linked lysosomal storage disorder caused by a reduced or absent activity of the enzyme iduronate 2-sulfatase. The clinical features and severity of symptoms of MPS II are widely variable ranging from severe disease to an attenuated form, which generally presents later in life with a milder clinical presentation. In general, symptoms may include coarse facial features, short stature, enlarged liver and spleen, hoarse voice, stiff joints, cardiac disease, and profound neurologic involvement leading to developmental delays and regression. The clinical presentation of MPS II is similar to that of MPS I with the notable difference of the lack of corneal clouding in MPS II. Due to the x-linked inheritance pattern, MPS II is observed almost exclusively in males with an estimated incidence of 1 in 170,000 male births. Symptomatic carrier females have been reported, but are very rare. Treatment options include hematopoietic stem cell transplantation and enzyme replacement therapy

 

MPS-III, Sanfilippo syndrome is caused by a reduced or absent activity of 1 of 4 enzymes involved in heparan sulfate degradation. Patients with MPS III uniformly excrete heparan sulfate resulting in similar clinical phenotypes, and are further classified as type A, B, C, or D based upon the specific enzyme deficiency. Sanfilippo syndrome is characterized by severe central nervous system (CNS) degeneration, but only mild physical disease. Such disproportionate involvement of the CNS is unique among the MPSs. Onset of clinical features, most commonly behavioral problems and delayed development, usually occurs between 2 and 6 years in a child who previously appeared normal. Severe neurologic degeneration occurs in most patients by 6 to 10 years of age accompanied by a rapid deterioration of social and adaptive skills. Death generally occurs by the 20s. The occurrence of MPS III varies by subtype with types A and B being the most common and types C and D being very rare. The collective incidence is approximately 1 in 58,000 live births.

 

MPS IVA, Morquio A syndrome is caused by a reduced or absent N-acetylgalactosamine-6-sulfate sulfatase. Clinical features and severity of symptoms of MPS IVA are widely variable, but may include skeletal dysplasia, short stature, dental anomalies, corneal clouding, respiratory insufficiency, and cardiac disease. Intelligence is usually normal. Estimates of the incidence of MPS IVA syndrome range from 1 in 200,000 to 1 in 300,000 live births. Treatment with enzyme replacement therapy is available.

 

MPS IVB, Morquio B syndrome is caused by a reduced or absent beta-galactosidase activity, which gives rise to the physical manifestations of the disease. Clinical features and severity of symptoms of MPS IVB are widely variable ranging from severe disease to an attenuated form which generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, short stature, enlarged liver and spleen, hoarse voice, stiff joints, cardiac disease, but no neurological involvement. The incidence of MPS IVB is estimated to be about 1 in 250,000 live births. Treatment options are limited to symptomatic management.

 

MPS VI; Maroteaux-Lamy syndrome is an autosomal recessive lysosomal storage disorder caused by the deficiency of the enzyme arylsulfatase B. Clinical features and severity of symptoms are widely variable, but typically include short stature, dysostosis multiplex, facial dysmorphism, stiff joints, claw-hand deformities, carpal tunnel syndrome, hepatosplenomegaly, corneal clouding, and cardiac defects. Intelligence is usually normal. Rapidly progressing forms have an early onset of symptoms, significantly elevated GAGs especially dermatan sulfate, and can lead to death before the second or third decade. A more slowly progressing form has a later onset, milder skeletal manifestations, smaller elevations of GAGs, and typically a longer lifespan. Estimates of the incidence of MPS VI range from 1 in 250,000 to 1 in 300,000. Treatment options include hematopoietic stem cell transplantation andenzyme replacement therapy.

 

Elevations of dermatan and/or heparan sulfate are seen in MPS types I, II, III, and VI.

 

Elevations of keratan sulfate are seen in MPS IV.

Reference Values

DERMATAN SULFATE (DS)

Newborn-≤2 weeks: ≤200 nmol/L

>2 weeks: ≤130 nmol/L

 

HEPARAN SULFATE (HS)

Newborn-≤2 weeks: ≤96 nmol/L

>2 weeks: ≤95 nmol/L

 

TOTAL KERATAN SULFATE (KS)

≤5 years: ≤1,900 nmol/L

6-10 years: ≤1,750 nmol/L

11-15 years: ≤1,500 nmol/L

>15 years: ≤750 nmol/L

Interpretation

Elevations of dermatan sulfate and/or heparan sulfate may be indicative of one of the mucopolysaccharidoses types I, II, III, or VI.

 

Elevations of keratan sulfate may be indicative of mucopolysaccharidoses type IV.

Clinical Reference

1. de Ruijter J, de Ru MH, Wagemans T, et al: Heparan sulfate and dermatan sulfate derived disaccharides are sensitive markers for newborn screening for mucopolysaccharidoses types I, II and III. Mol Genet Metab 2012;107:705-710

2. de Ru MH, van der Tol L, van Vlies N, et al: Plasma and urinary levels of dermatan sulfate and heparan sulfate derived disaccharides after long-term enzyme replacement (ERT) in MPS I: correlation with the timing of ERT and with total urinary excretion of glycosaminoglycans. J Inherit Metab Dis 2013;36:247-255

3. Osago H, Shibata T, Hara N, et al: Quantitative analysis of glycosaminoglycans, chondroitin/dermatan sulfate, hyaluronic acid, heparan sulfate, and keratan sulfate by liquid chromatography-electrospray ionization-tandem mass spectrometry. Anal Biochem 2014;467:62-74

Day(s) and Time(s) Performed

Monday, Wednesday, Friday; 9 a.m

Analytic Time

2 days

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

82542

LOINC Code Information

Test ID Test Order Name Order LOINC Value
MPSBS Mucopolysaccharidosis, BS In Process

 

Result ID Test Result Name Result LOINC Value
43695 Interpretation (MPSBS) 59462-2
43693 Dermatan Sulfate In Process
43694 Heparan Sulfate In Process
BA2869 Total Keratan Sulfate In Process
43696 Reviewed By 18771-6

Forms

1. New York Clients-Informed consent is required. Please document on the request form or electronic order that a copy is on file. An Informed Consent for Genetic Testing (T576) is available in Special Instructions.

2. Biochemical Genetics Patient Information (T602) in Special Instructions.

Testing Algorithm

See Newborn Screen Follow-up for Mucopolysaccharidosis Type I in Special Instructions.

 

For more information, see Newborn Screening Act Sheet Mucopolysaccharidosis Type I: Decreased Alpha-L-Iduronidase in Special Instructions.