Hurler Syndrome (MPS I): Alpha-iduronidase Enzyme Analysis

Clinical Information

Mucopolysaccharidosis type I (MPSI) is caused by deficient alpha-iduronidase enzyme activity, which results in an accumulation of the glycoamnioglycan heparan sulfate and dermatan sulfate in body tissues. MPS I is a multisystem progressive disorder demonstrating wide phenotypic variability with three different MPSI subtypes described (Hurler, Hurler-Scheie, and Scheie). Hurler syndrome is considered the more severe end of the phenotypic spectrum with patients generally diagnosed before 18 months of age while Hurler-Scheie and Scheie syndromes are usually used to describe the milder phenotypes. These less severe cases, also known as attenuated MPS I, will often present between 3 and 10 years of age. Clinical features of MPS I include coarse facial features, dysostosis multiplex, short stature, hirsutism, cloudy corneas, and hepatosplenomegaly, and cardiac comlications. Developmental delay and intellectual disability is more severe in those patients with Hurler syndrome and is a distinguishing feature between the subtypes of MPS I.

Technical Information

Alpha-iduronidase enzyme activity is measured using a 4-methylumbelliferyl (4-MU) substrate (leukocytes, plasma, fibroblasts) or liquid chromatography-tandem mass spectrometry (LC-MS/MS) (DBS).

Specimen Requirements

• Accepted sample types for this test include dried blood spots (DBS), fibroblasts, leukocytes, and plasma.
• DBS: Approximately 75 uL of blood should be applied to each of the five circles on filter paper dried blood spot card. Allow blood to dry for at least 4 hours before shipping.
• Fibroblasts: Tissue sample should be stored in sterile culture media; cultured fibroblasts should be sent in two T25 flasks. Do NOT place tissue in formalin or formaldehyde. Do not freeze tissue.
• Leukocytes: A minimum of 5 mL whole blood (7-10 mL preferred) collected in a sodium heparin tube.
• Plasma: A minimum of 3 mL whole blood collected in a sodium heparin tube; or blood can be centrifuged and a minimum of 1 mL plasma removed and sent for analysis.

Transport Instructions

• DBS: Ship DBS card at ambient temperature.
• Fibroblasts: Ship tissue sample or cultured fibroblasts at ambient temperature.
• Leukocytes: Whole blood should be shipped at ambient temperature. If leukocytes are being isolated at another laboratory, the pellet should be frozen after specimen processing and shipped frozen on dry ice.
• Plasma: Plasma should be frozen after collection and shipped frozen, preferably on dry ice. Whole blood should be shipped at ambient temperature.