Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed. Hurler syndrome is the most severe form of mucopolysaccharidosis type 1 MPS1; see this term , a rare lysosomal storage disease, characterized by skeletal abnormalities, cognitive impairment, heart disease, respiratory problems, enlarged liver and spleen, characteristic facies and reduced life expectancy. Patients present within the first year of life with musculoskeletal alterations including short stature, dysostosis multiplex, thoracic-lumbar kyphosis, progressive coarsening of the facial features including large head with bulging frontal bones, depressed nasal bridge with broad nasal tip and anteverted nostrils, full cheeks and enlarged lips , cardiomyopathy and valvular abnormalities, neurosensorial hearing loss, enlarged tonsils and adenoids, and nasal secretion.
|Published (Last):||2 September 2010|
|PDF File Size:||6.37 Mb|
|ePub File Size:||11.45 Mb|
|Price:||Free* [*Free Regsitration Required]|
Alternative titles; symbols. The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans GAGs , or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function.
Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression McKusick, McKusick et al. The clinical features of Hurler syndrome include coarse facies, corneal clouding, mental retardation, hernias, dysostosis multiplex, and hepatosplenomegaly.
Children with Hurler syndrome appear normal at birth and develop the characteristic appearance over the first years of life Wraith et al. Wraith et al. Diagnosis was established at a mean age of 21 months range, months. The average age at death was 6. Cleary and Wraith described the presenting features of 39 patients with mucopolysaccharidosis type IH. The mean age at diagnosis was approximately 9 months in this study.
An earlier age at diagnosis is likely to lead to better results following therapy such as bone marrow transplantation. Clinical features that should arouse suspicion of MPS IH include frequent ear, nose and throat surgery and recurrent hernias. McDowell et al. The cases underscored the need for caution in counseling and the limitations of using sibs as controls in evaluating the outcome of treatment.
Gorlin et al. A slight coarsening of the facial features at 3 to 6 months of age is usually the first abnormality detected. The head is large with bulging frontal bones. The skull is often scaphocephalic secondary to premature closure of the metopic and sagittal sutures. The nasal bridge is depressed with broad nasal tip and anteverted nostrils.
The cheeks are full. The lips are enlarged and the mouth is usually held open, particularly after age 3 years. Chronic nasal discharge is present. Corneal clouding is common. Optic nerve head swelling was observed in 8 of 14 eyes of Hurler syndrome patients reported by Collins et al. Huang et al. The first patient 28 years old exhibited multifocal depigmented retinopathy in both eyes.
The second patient 12 years old had mild parafoveal retinal folds and mild swollen discs in both eyes. The third patient 33 years old had a myelinated nerve fiber layer in the right eye. In the first patient, spectal-domain optical coherence tomography SD-OCT showed focal choroidal thinning in the depigmented retinopathy areas.
In the other 2 patients, SD-OCT showed a fuzzy and thickened external limiting membrane at the fovea. The neck is short and there is odontoid hypoplasia. Vertebral subluxation with cord compression can occur Thomas et al. In a review of cervical spine x-rays in 21 children with mucopolysaccharidosis, Belani et al.
Cardiac disease is common. Acute cardiomyopathy associated with endocardial fibroelastosis has been a presenting condition in some infants with MPS I less than 1 year of age Donaldson et al. Krovetz et al. There was valvular involvement in 40 of 58 cases, coronary artery narrowing in 20 of 58 patients, and endocardial fibroelastosis in 11 of 58 patients. They suggested that coronary insufficiency can occur but that Hurler patients are prohibited by their retarded development to communicate this effectively.
Renteria et al. All had narrowing of the extramural coronary arteries, cardiac valve thickening left-sided greater than right-sided , generalized thickening of mural endocardium, and 'stiffening' of the myocardial walls. Wippermann et al. Aortic and mitral valve thickening was also detected in the patients. Frequent upper and lower respiratory tract infections are common. Respiratory obstruction occurs secondary to enlargement of tonsils and adenoids Shapiro et al.
Narrow tracheas also contribute to upper airway construction. Peters et al. Autopsy of an MPS IH patient whose tracheal diameter measured 5 mm revealed that the epiglottis, aryepiglottic folds, and the vocal cords were enlarged and mainstem bronchi were thickened.
This resulted primarily from glycosaminoglycan deposition in the connective tissues. All had tonsillar and adenoidal hypertrophy, tongue enlargement, and supraglottic narrowing. Two patients studied by polysomnography had obstructive sleep apnea. Belani et al. They described anesthetic results in 14 patients with Hunter syndrome. During laryngoscopy, vocal cords were visible in only 19 of 55 anesthetic events. Following extubation, upper airway obstruction was noted 25 times.
Length is often normal until about 2 years of age when growth stops; by age 3 years height is less than the third percentile Gorlin et al. In infancy, bone trabeculation is coarse. In late infancy and childhood, a pattern of skeletal changes called 'dysostosis multiplex' develops McKusick, The skull is large with narrow orbits. The calvaria is thickened and the sagittal and lambdoidal sutures close prematurely. The sella becomes J-shaped. The ribs have been described as oar-shaped with narrowing at the vertebral ends and broadening at the sternal ends.
Clavicles are short, thick, and irregular. The vertebral bodies are dysplastic with biconcave endplates and hook-shaped configuration of the lower thoracic and upper lumbar vertebral bodies. The pelvis is poorly formed with small femoral heads and coxa valga. Iliac wings are flared. The long tubular bones show diaphyseal widening with small, deformed epiphyses.
Phalanges are bullet-shaped with proximal pointing of the second to fifth metacarpals. Neuhauser et al. Joint stiffness is a common feature of all the MPS disorders with the exception of Morquio syndrome ; The joint function abnormalities probably result from a combination of the metaphyseal deformities and thickened joint capsules secondary to glycosaminoglycan deposition and fibrosis Neufeld and Muenzer, Progressive lumbar gibbus or kyphosis is commonly seen in the MPS disorders Neufeld and Muenzer, Tandon et al.
High lumbar kyphosis was seen in 10 patients and was associated with thoracic scoliosis in 1. Isolated thoracic scoliosis was seen in another. One patient had no significant problems in the thoracic or lumbar spine but had odontoid hypoplasia, which was also seen in 3 other children. Four of the 8 patients in whom MRI of the cervical spine had been performed had abnormal soft tissue around the tip of the odontoid. Neurologic problems were seen in 2 patients. Carpal tunnel syndrome, a common complication in the mucopolysaccharidoses, probably results from a combination of excessive lysosomal storage in the connective tissue of the flexor retinaculum and a deformity secondary to the underlying skeletal dysplasia.
Wraith and Alani performed nerve conduction studies on 18 patients with various forms of mucopolysaccharidoses and mucolipidosis III. All patients studied, with the exception of patients younger than 2 years, had evidence of thenar muscle wasting and a typical 'claw-hand' deformity. Two of the 3 received bone marrow transplantation at 14 months and 2. Neither showed improvement following transplantation. Developmental delay is often apparent by 12 to 24 months of age, with a maximum functional age of 2 to 4 years followed by progressive deterioration.
Most children develop limited language because of developmental delay, chronic hearing loss, and enlarged tongue Neufeld and Muenzer, Only 5 children developed signs and symptoms of raised intracranial pressure which required shunt.
Lee et al. All exhibited cribriform or cystic changes: low signal intensity with respect to white matter on T1-weighted images and high-signal intensity on the T2-weighted images.
The changes corresponded pathologically to perivascular accumulations of glycosaminoglycan within the foam cells in the Virchow-Robin spaces Norman et al.
Myelination delay, atrophy, and ventricular enlargement were also found in their patients. Hanson et al. A literature analysis revealed 37 additional cases. The most common lysosomal storage disease associated with dermal melanocytosis was Hurler syndrome 24 of 39 cases , followed by GM1-gangliosidosis 11 of 39 cases.
The enzyme deficient in Hurler syndrome is alpha-L-iduronidase Danes and Bearn found that cellular accumulation of mucopolysaccharides persists in cultured fibroblasts. Fratantoni et al. Furthermore, they found that mixing of fibroblasts from Hurler and Hunter patients causes mutual correction of the intracellular accumulation of mucopolysaccharides.
Medium in which cells of the other type or normal cells had been incubated was also effective in correcting the defect.
Alternative titles; symbols. The mucopolysaccharidoses are a group of inherited disorders caused by a lack of specific lysosomal enzymes involved in the degradation of glycosaminoglycans GAGs , or mucopolysaccharides. The accumulation of partially degraded GAGs causes interference with cell, tissue, and organ function. Hurler and Scheie syndromes represent phenotypes at the severe and mild ends of the MPS I clinical spectrum, respectively, and the Hurler-Scheie syndrome is intermediate in phenotypic expression McKusick, McKusick et al. The clinical features of Hurler syndrome include coarse facies, corneal clouding, mental retardation, hernias, dysostosis multiplex, and hepatosplenomegaly. Children with Hurler syndrome appear normal at birth and develop the characteristic appearance over the first years of life Wraith et al.
2015, Número 1
Hurler syndrome is one of the mucopolysaccharidoses MPS type I. It manifests in the first years of life with intellectual disability, corneal clouding, deafness, and cardiac disease. Death usually occurs within the first decade of life, often from cardiac disease. It is named after Gertrud Hurler , a German pediatrician 1. Please Note: You can also scroll through stacks with your mouse wheel or the keyboard arrow keys.