Genetics of Mucopolysaccharidosis Type VI Workup
- Author: Paul R Harmatz, MD; Chief Editor: Maria Descartes, MD more...
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- Urine glycosaminoglycan analysis can be performed using various qualitative or quantitative methods. These studies are useful for establishing the likely diagnosis of mucopolysaccharidosis (MPS) but do not provide a specific diagnosis, which requires enzymatic testing.
- Definitive diagnosis requires the determination of the specific lysosomal enzyme level in cultured fibroblasts or isolated leukocytes.
- Normal levels of a second sulfatase should be documented to exclude multiple sulfatase deficiency.
- Mutational analysis of the ARSB gene should be considered if the diagnosis is in question.[8, 9]
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- Perform skeletal survey studies to reveal dysostosis multiplex. Findings may include the following:
- Macrocephaly with an enlarged j-shaped sella
- Thickened, short metacarpal bones with proximal pointing and thin cortices
- Paddle-shaped, widened ribs
- Short, thick irregular clavicles
- Dysplastic femoral head
- Severe hip dysplasia
- Ovoid deformities of the vertebrae
- Anterior hypoplasia of the L1 and L2 vertebral bodies
- Evidence of kyphoscoliosis
- Echocardiography can reveal valvular heart disease, which is common. Acute infantile cardiomyopathy has also been reported in mucopolysaccharidosis type VI (MPS VI).
- MRI of the brain and spine may demonstrate hydrocephalus or provide evidence for spinal cord compression and spinal cord malacia, especially in the cervical region.
- Flexion-extension radiography of the C-spine may demonstrate atlantoaxial instability and subluxation of C1 on C2; CT scanning may be necessary if radiograph images are not clearly interpretable.
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- Perform an audiological evaluation because deafness and hearing loss are common in MPS.
- Perform an ophthalmologic examination to identify corneal opacities, vision change, and optic nerve abnormalities, suggesting increased intracranial pressure.
- Perform pulmonary function tests to monitor restrictive and obstructive disease and perform a sleep study to evaluate for sleep apnea.
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- Lysosomal engorgement in tissue biopsies is evident, as are vacuolated lymphocytes on peripheral blood smear.
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- Urine glycosaminoglycan (GAG) level corrected for creatinine is a biochemical disease marker that can provide a crude estimate of disease severity and response to specific treatment (hematopoietic stem cell transplant [HSCT ] or enzyme replacement therapy).
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