Diagnosis of mucopolysaccharidosis I, Hurler, Scheie, and Hurler-Scheie syndromes in whole blood
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
The mucopolysaccharidoses (MPS) are a group of lysosomal storage disorders caused by the deficiency of any of the enzymes involved in the stepwise degradation of dermatan sulfate, heparan sulfate, keratan sulfate, or chondroitin sulfate (glycosaminoglycans; GAG). Accumulation of GAG (previously called mucopolysaccharides; MPS) in lysosomes interferes with normal functioning of cells, tissues, and organs. There are 11 known disorders that involve the accumulation of GAG. MPS disorders involve multiple organ systems characterized by coarse facial features, cardiac abnormalities, organomegaly, intellectual disabilities, short stature, and skeletal abnormalities.
Mucopolysaccharidosis I (MPS I) is an autosomal recessive disorder caused by a reduced or absent activity of the enzyme alpha-L-iduronidase due to mutations in the IDUA gene. More than 100 mutations have been reported in individuals with MPS I. Deficiency of alpha-L-iduronidase can result in a wide range of phenotypes categorized into 3 syndromes: Hurler syndrome (MPS IH), Scheie syndrome (MPS IS), and Hurler-Scheie syndrome (MPS IH/S). Because these syndromes cannot be distinguished biochemically, they are also referred to as MPS I and attenuated MPS I.
Clinical features and severity of symptoms of MPS I are variable, ranging from severe disease to an attenuated form that generally presents at a later onset with a milder clinical presentation. In general, symptoms may include coarse facies, progressive dysostosis multiplex, hepatosplenomegaly, corneal clouding, hearing loss, intellectual disabilities or learning difficulties, and cardiac valvular 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.
A diagnostic workup in an individual with MPS I typically demonstrates elevated levels of urinary GAG (MPSQN / Mucopolysaccharides [MPS], Quantitative, Urine) and increased amounts of both dermatan and heparan sulfate detected on thin-layer chromatography (MPSSC / Mucopolysaccharides [MPS] Screen, Urine). Reduced or absent activity of alpha L-iduronidase in blood spots (IDSBS / Alpha-L-Iduronidase, Blood Spot), fibroblasts (IDST / Alpha-L-Iduronidase, Fibroblasts), leukocytes, or whole blood can confirm a diagnosis of MPS I; however, enzymatic testing is not reliable for carrier detection. Molecular sequence analysis of the IDUA gene allows for detection of the disease-causing mutation in affected patients and subsequent carrier detection in relatives. To date, a clear genotype-phenotype correlation has not been established.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or = 1.0 nmol/h/mL
An interpretive report will be provided.
Specimens with results <1.0 nmol/h/mL in properly submitted specimens are consistent with alpha-L-iduronidase deficiency (mucopolysaccharidosis I). Further differentiation between Hurler, Scheie, and Hurler-Scheie is dependent on the clinical findings.
Normal results (> or =1.0 nmol/h/mL) are not consistent with alpha-L-iduronidase deficiency.
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
The presence of a pseudodeficiency allele may cause reduced activity of alpha-L-iduronidase in the artificial substrate used in this assay. This can result in values below the normal reference range, but will typically be greater than levels found in patients with mucopolysaccharidosis I (MPS I).
This test cannot reliably determine carrier status for MPS I.
This test does not differentiate between Hurler and Scheie syndromes.
Clinical Reference Provides recommendations for further in-depth reading of a clinical nature
1. Neufeld EF, Muenzer J: The mucopolysaccharidoses. In The Metabolic and Molecular Basis of Inherited Disease. Vol 3. Eighth edition. Edited by CR Scriver, AL Beaudet, WS Sly, et al. McGraw-Hill, Medical Publishing Division, 2001, pp 3421
2. Chamoles NA, Blanco M, Gaggioli D, Casentini C: Hurler-like phenotype: enzymatic diagnosis in dried blood spots on filter paper. Clin Chem 2001;47:2098-2102
3. Martins AM, Dualibi AP, Norato D, et al: Guidelines for the management of mucopolysaccharidosis type I. J Pediatr 2009 Oct;155(4 Suppl):S32-46
4. Enns GM, Steiner RD, Cowan TM: Lysosomal disorders: mucopolysaccharidoses. In Pediatric Endocrinology and Inborn Errors of Metabolism. Edited by K Sarafoglou, GF Hoffmann, KS Roth. McGraw-Hill, Medical Publishing Division, 2009, pp 721-730
5. Clarke LA, Heppner J: Mucopolysaccharidosis Type I. GeneReviews. Edited by RA Pagon, TD Bird, CR Dolan, et al. University of Washington, Seattle. Last updated July 2011