English Version
J. Stelzner, T. Terboven

Hurler syndrome

Hurler syndrome

Schlüsselwörter Hurler syndrome; ICD 10: E 76.0; Mucopolysaccharidosis (MPS) I-H, α-L-iduronidase deficiency; Pfaundler-Hurler syndrome
Keywords Hurler syndrome; ICD 10: E 76.0; Mucopolysaccharidosis (MPS) I-H, α-L-iduronidase deficiency; Pfaundler-Hurler syndrome
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Hurler syndrome is a rare lysosomal storage disease belonging to the group of mucopolysaccharidoses type I (MPS I) with an autosomal recessive transmission. MPS I is subdivided into three phenotypes of increasing severity: Scheie syndrome being the mildest, Hurler-Scheie syndrome (MPS I-HS) intermediate and Hurler syndrome (MPS I-H) the most severe. The genetic defect in MPS I-H results in a complete deficiency of the enzyme α-L-iduronidase. This leads to progressive accumulation of glycosaminoglycans causing multi-organ dysfunction. Prevalence of MPS I-H is estimated at  0.7-1.6/100,000.

Patients presenting with MPS I-H have progressive cognitive impairment and somatic disorders. The skeletal abnormalities (cervical spine instability, loss of joint range of motion, restricted mobility, growth slowing or arrest in childhood, short stature, typical facial features with a short and stiff neck) seen in these patients are collectively referred to as dysostosis multiplex. Other signs and symptoms include cardiac disease (cardiomyopathies, valvular dysfunction), restrictive lung disease, frequent and recurrent respiratory infections, different types of hernias, communicating hydrocephalus, compression of the spinal cord, corneal clouding, loss of hearing and all types of organomegaly. The airway is obstructed at all levels due to hypertrophy of the soft tissue with narrowed nasal passage, adenotonsillar hypertrophy, macroglossia and thickened laryngeal and pharyngeal structures, subglottic narrowing and tracheobronchomalacia. These pathologies often result in severe obstructive sleep apnoea (OSA). There might also be odontoid dysplasia and stiff temporomandibular joint with reduced mouth opening.

Life expectancy for untreated MPS I-H is usually under 10 years. Although haematopoietic stem cell transplantation is associated with several risks, it is the only therapeutic option to preserve intellectual development and also improves cardiac and respiratory function and the problems of airway obstruction. It has to be performed before the age of 2 years. Skeletal abnormalities show no improvement.

The enzyme substitute (laronidase) obtained EU marketing authorisation as an Orphan drug in 2003. Given through weekly infusions, it leads to improvement of lung function and joint mobility. However, the neuropsychological manifestations are not influenced by enzyme replacement therapy.


Supplements OrphanAnesthesia