Laboratory Studies

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]}

Imaging Studies

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), also known as Maroteaux-Lamy syndrome.

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.

Other Tests

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.

Histologic Findings

Lysosomal engorgement in tissue biopsies is evident, as are vacuolated lymphocytes on peripheral blood smear.

Staging

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).

Treatment & Management

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Author

Paul R Harmatz, MD Attending Physician, Department of Gastroenterology and Nutrition, Children’s Hospital Oakland

Paul R Harmatz, MD is a member of the following medical societies: American Gastroenterological Association

Disclosure: Received consulting fee from BioMarin Pharmaceutical Inc. for consulting; Received honoraria from BioMarin Pharmaceutical Inc. for speaking and teaching; Received advisory board from BioMarin Pharmceutical Inc. for board membership; Received consulting fee from Shire Human Genetic Therapies for board membership; Received honoraria from Shire Human Genetic Therapies for speaking and teaching; Received honoraria from Genzyme for speaking and teaching; Received grant/research funds from BioMarin Ph.

Coauthor(s)

Margaret M McGovern, MD, PhD Professor and Chair of Pediatrics, Stony Brook University School of Medicine

Margaret M McGovern, MD, PhD is a member of the following medical societies: American Academy of Pediatrics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Maria Descartes, MD Professor, Department of Human Genetics and Department of Pediatrics, University of Alabama at Birmingham School of Medicine

Maria Descartes, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Medical Genetics and Genomics, American Medical Association, American Society of Human Genetics, Society for Inherited Metabolic Disorders, International Skeletal Dysplasia Society, Southeastern Regional Genetics Group

Disclosure: Nothing to disclose.

Additional Contributors

Karl S Roth, MD Retired Professor and Chair, Department of Pediatrics, Creighton University School of Medicine

Karl S Roth, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Pediatrics, American College of Nutrition, American Pediatric Society, American Society for Nutrition, American Society of Nephrology, Association of American Medical Colleges, Medical Society of Virginia, New York Academy of Sciences, Sigma Xi, The Scientific Research Honor Society, Society for Pediatric Research, Southern Society for Pediatric Research

Disclosure: Nothing to disclose.