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Mucopolysaccharidosis type 4Direct access to data Alias
Mucopolysaccharidosis type IV (MPS IV) or Morquio disease is a lysosomal storage disease belonging to the group of mucopolysaccharidoses, and characterised by spondylo-epiphyso-metaphyseal dysplasia. It exists in two forms, A et B. Prevalence is approximately 1/250 000 for type IVA, with highly variable incidences according to different countries. MPS IVB is even rarer. MPS IVA is a spondylo-epiphyso-metaphyseal dysplasia generally diagnosed during the second year of life, after walking acquisition. Skeletal deformities (platyspondyly, kyphosis, scoliosis, pectus carinatum, genu valgum, long bones deformity) become more pronounced as the child grows. Joint hyperlaxity is accompanied by frequent luxations (hips, knees). The skeletal involvement not only leads to impairment in walking and daily activities, but also to growth arrest around the age of 8 and a definite size of 1m to 1.50m, depending on the severity of the disease. Potential nervous complications are secondary to skeleton deformations. Ever since the age of 5 or 6 years, the hypoplasia of the odontoid vertebra combined with joint hyperlaxity leads to an instability at the level of the first two cervical vertebra, with a risk of bone marrow compression. Extra-skeletal manifestations include respiratory problems, hepatomegaly, valvulopathies, hearing loss and corneal clouding. Intelligence is normal. The clinical picture is quite similar in type IV B and both forms cannot be clinically distinguished, the severity of symptoms varying for each type. Deficiency in one of the two enzymes required for the degradation of keratan sulfate (KS) is responsible for MPS IV subtypes: N-acetylgalactosamine-6-sulfate sulfatase in MPS IVA, and beta-D-galactosidase in MPS IVB. The genes coding for both enzymes have been located and cloned (GALNS is on 16q24 and GLB1 on 3p) and mutations have been identified (118 for GALNS). Transmission is autosomal recessive in both cases. Diagnosis is based on detection of increased urinary KS excretion (not constant) and galactosyloligoaccharides excretion in MPS IVB and confirmed by the demonstration of enzymatic deficiency in cultured leucocytes or fibroblasts. Enzymatic study allows other osteochondrodysplasies to be excluded. The distinction between MPS IVB and GM1 gangliosidose type 3 (see this term) is often difficult in children, even if 9 out of 59 mutations of GLB1 gene are associated to MPS IVB. Heterozygous individuals can be detected in the family when the two mutations have been identified in the index patient. In families wishing to benefit from prenatal diagnosis, it can be performed after trophoblast sampling or amniocentesis by assessing the activity of the deficient enzyme or by investigating the mutations identified in the index patient. General anaesthesia is delicate in patients with MPS type IV, due to intubation difficulties. Allogenic bone marrow transplant having not proven its efficacy on bone disorders, treatment is symptomatic, mainly through physiotherapy and orthopaedic measures (fitting with a prosthesis, surgery, essentially neck consolidation by vertebral fusion). A therapy by infusion of bone tissue-targeted recombinant enzyme is currently being developed. Prognosis depends on the severity of the disease and on the quality of management which can allow to survive beyond the age of 50. *Authors: Drs I. Maire & R. Froissart (February 2007)*. Clinical signs
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