Scheie Syndrome

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Retrieved

2021-01-23

Source

Orphanet

Trials

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Genes

IDUA, SLC26A1

Drugs

6'-(R)-methyl-5-O-(5-amino-5,6-dideoxy-alpha-L-talofuranosyl)-paromamine sulfate, Adeno-associated viral vector serotype 2/6 encoding zinc-finger nucleases and the human alpha L-iduronidase gene, Allogeneic multi-virus specific T lymphocytes targeting BK virus, cytomegalovirus, human herpesvirus-6, Epstein Barr virus and adenovirus, Laronidase ( ALDURAZYME ), Recombinant adeno-associated viral vector serotype 9 containing human iduronidase gene, Recombinant human insulin receptor monoclonal antibody-fused-alpha-L-iduronidase, autologous CD34+ haematopoietic stem and progenitor cells genetically modified with the lentiviral vector IDUA LV, encoding for the alpha-L-iduronidase cDNA, haematopoietic stem cells and blood progenitors umbilical cord-derived expanded with (1R, 4R)-N1-(2-benzyl-7-(2-methyl-2H-tetrazol-5-yl)-9H-pyrimido[4,5-b]indol-4-yl)cyclohexane-1,4-diamine dihydrobromide dihydrate

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Scheie syndrome is the mildest form of mucopolysaccharidosis type 1 (MPS1; see this term), a rare lysosomal storage disease, characterized by skeletal deformities and a delay in motor development.

Epidemiology

Prevalence is estimated at 1/500,000.

Clinical description

Symptoms commonly occur after the age of 5 years but are so mild that diagnosis is often not considered until adulthood. Patients are of almost normal height and do not show intellectual deficiency. Corneal opacification occurs progressively and diffusely, usually after the age of four years. Glaucoma is more frequent than in Hurler syndrome (see this term). Patients present with mild coarsening of the facial features, including a large mouth with thick lips. Patients may present with nasal secretion, neurosensorial hearing loss, stiff joints, mild skeletal changes and carpal tunnel syndrome. Aortic valve disease may be present. Compression of the cervical spinal cord, caused by glycosaminoglycan infiltration of the dura, may lead to spastic paresis if not corrected by neurosurgical intervention.

Etiology

Scheie syndrome is caused by mutations in the IDUA gene (4p16.3) leading to partial deficiency in the alpha-L-iduronidase enzyme and lysosomal accumulation of dermatan sulfate and heparan sulfate.

Diagnostic methods

Early diagnosis is difficult because the first clinical signs are not specific, but is very important to allow early treatment. Diagnosis is based on detection of increased urinary secretion of heparan and dermatan sulfate through the 1,9-dimethylmethylene blue (DMB) test and glycosaminoglycan (GAG) electrophoresis, and demonstration of enzymatic deficiency in leukocytes or fibroblasts. Genetic testing is available.

Differential diagnosis

Differential diagnoses include the more severe forms of mucopolysaccharidosis type 1, Hurler-Scheie syndrome and Hurler syndrome, and mucopolysaccharidosis type VI and mucopolysaccharidosis type II (see these terms).

Antenatal diagnosis

Antenatal diagnosis is possible by measurement of enzymatic activity in cultivated chorionic villus or amniocytes and by genetic testing if the disease-causing mutation is known.

Genetic counseling

Transmission is autosomal recessive. Genetic counseling is recommended.

Management and treatment

Management should be carried out by a multidisciplinary team and should include physiotherapy to maintain range of movement. The enzyme substitute (laronidase) obtained EU marketing authorization as an orphan drug in 2003. Given through weekly infusions it leads to improvement of lung function and joint mobility. Enzyme replacement therapy (ERT) should be started at diagnosis and may be beneficial in patients awaiting hematopoietic stem cell transplantation (HSCT). Early treatment slows the progression of the disease.

Prognosis

Life expectancy for patients with Scheie syndrome may only be slightly affected.