Synonym: mucopolysaccharidosis type IH, mucopolysaccharidosis I, MPS I

The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans (GAGs). Deficiency of alpha-L-iduronidase can result in a wide range of phenotypes including Hurler's (severe), Scheie's (mild) and Hurler-Scheie (intermediate) syndromes.¹ The genetic defect involves a mutation in the gene IDUA that encodes alpha-L-iduronidase on chromosome 4.²

Epidemiology

• One study, using a unique longitudinal data set, initiated and maintained over a period of more than 20 years by the Society for Mucopolysaccharide Diseases (UK), found a birth prevalence in England and Wales of 1.07/100,000.³
• The mode of inheritance is autosomal recessive.

Presentation

Affected children appear normal at birth but usually develop the characteristic appearance within the first year of life.

• Mental retardation: maximum functional development is reached when the child is aged between 2 and 4 years²
• Short stature
• Coarse facies and enlarged tongue
• Corneal clouding
• Hearing impairment
• Umbilical and inguinal hernias
• Joint stiffness and skeletal deformities
• Cardiomyopathy and coronary heart disease
• Hepatosplenomegaly
• Dysostosis multiplex: enlarged skull, enlarged but shortened bones, malformed pelvis, and other skeletal defects

Differential diagnosis

• Other mucopolysaccharidoses: Hunter's syndrome (mucopolysaccharidosis type II) has no corneal clouding and progression is slower.
• Other causes of mental retardation and short stature.

Investigations

• Urine: raised levels of dermatan sulfate and heparan sulfate (metabolites related to GAG) are found in patients with mucopolysaccharidoses.
• Lymphocytes examined in blood smears may show abnormal cytoplasmic inclusions.
• Definitive diagnosis is established by alpha-L-iduronidase enzyme assay using artificial substrates in cultured fibroblasts or isolated leukocytes.
• Carrier testing can be performed by differentiating normal enzyme activity from half-normal levels of enzyme activity.
• Prenatal diagnosis: using cultured amniotic fluid cells or chorionic villus biopsies.
• Molecular diagnosis: difficult because of genetic heterogeneity.
• Assessment of complications will include an echocardiogram and MRI brain scan.
• In severe cases, radiography of the skeleton (especially the spine) may detect a gibbus deformity of the lower spine.
• A mild form of dysostosis multiplex may be seen on X-ray.⁴
• Ultrasound imaging of the ophthalmic nerve sheath and sclera is a useful technique for assessing the presence of morphological changes.⁵

Management

• Palliative treatment includes the provision of multidisciplinary treatment and support for affected children and their families.
• Orthopaedic surgery for joint contractures and skeletal deformities.
• Other surgical procedures may include myringotomy, hernia repair and adenoidectomy/tonsillectomy.⁶
• Corneal transplants may be required.
• Enzyme replacement: laronidase is licensed for long-term replacement therapy in the treatment of non-neurological manifestations of Hurler's syndrome; it may reduce the excess carbohydrates stored in organs and lead to some functional improvements.
• Allogenic marrow transplant and gene therapy may present treatment possibilities in the future.

Complications

• Orthopaedic complications lead to pain and immobility.
• Upper airways obstruction.
• Increased susceptibility to infections of the respiratory tract.

Prognosis

• The median survival for mucopolysaccharidosis I (MPS I) patients is 11.6 years.³
• Common causes of death include upper airways obstruction, cardiac insufficiency and respiratory tract infections.

Document references

1. Mucopolysaccharidosis Type IH, Online Mendelian Inheritance in Man (OMIM)
2. Nash D; Mucopolysaccharidosis Type IH. eMedicine.com, 2009.
3. Moore D, Connock MJ, Wraith E, et al; The prevalence of and survival in Mucopolysaccharidosis I: Hurler, Hurler-Scheie Orphanet J Rare Dis. 2008 Sep 16;3:24. [abstract]
4. Gillespie J; J Bone Joint Surg Am. 1940; 22:171-175.
5. Schumacher RG, Brzezinska R, Schulze-Frenking G, et al; Sonographic ocular findings in patients with mucopolysaccharidoses I, II and VI. Pediatr Radiol. 2008 May;38(5):543-50. Epub 2008 Feb 26. [abstract]
6. Arn P, Wraith JE, Underhill L; Characterization of surgical procedures in patients with mucopolysaccharidosis J Pediatr. 2009 Jun;154(6):859-64.e3. Epub 2009 Feb 12. [abstract]

Acknowledgements