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Mucopolysaccharidosis Type IVA.

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GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2020.
2013 Jul 11 [updated 2016 Mar 24].

Author information

1
Children’s National Medical Center, Washington, DC

Excerpt

CLINICAL CHARACTERISTICS:

The phenotypic spectrum of mucopolysaccharidosis IVA (MPS IVA) is a continuum that ranges from a severe and rapidly progressive early-onset form to a slowly progressive later-onset form. Children with MPS IVA have no distinctive clinical findings at birth. The severe form is usually apparent between ages one and three years, often first manifesting as kyphoscoliosis, knock-knee (genu valgum), and pectus carinatum; the slowly progressive form may not become evident until late childhood or adolescence often first manifesting as hip problems (pain, stiffness, and Legg Perthes disease). Progressive bone and joint involvement leads to short stature, and eventually to disabling pain and arthritis. Involvement of other organ systems can lead to significant morbidity, including respiratory compromise, obstructive sleep apnea, valvular heart disease, hearing impairment, visual impairment from corneal clouding, dental abnormalities, and hepatomegaly. Compression of the spinal cord is a common complication that results in neurologic impairment. Children with MPS IVA have normal intellectual abilities at the outset of the disease.

DIAGNOSIS/TESTING:

The diagnosis of MPS IVA is established by analysis of N-acetylgalactosamine 6-sulfatase (GALNS) enzyme activity or by the identification of biallelic pathogenic variants in GALNS on molecular genetic testing.

MANAGEMENT:

Treatment of manifestations: Enzyme replacement therapy (elosulfase alfa, or Vimizim™) is available, although the long-term effects of this treatment on the skeletal and non-skeletal features of MPS IVA are not yet known. Evaluation and management of individuals with MPS IVA are best undertaken by multiple specialists, coordinated by a physician specializing in the care of persons with complex medical problems. Physiatrists, physical therapists, and occupational therapists help optimize mobility and autonomy. Psychological support can optimize coping skills and quality of life; educational professionals can optimize the learning environment for a medically fragile individual. Surgical intervention is often required for lower extremity malalignment, hip subluxation and/or hip pain, upper cervical spine instability, and/or progressive thoracolumbar kyphosis. Upper extremity management may include stabilizing external wrist splints or partial or complete wrist fusion. Cardiac valve involvement may require placement of a bioprosthetic or prosthetic valve. Upper-airway obstruction and obstructive sleep apnea are managed by removal of enlarged tonsils and adenoids; diffuse narrowing of the airway may require positive airway pressure and/or tracheostomy. The outcome following keratoplasty for corneal opacification varies. Hearing loss is often treated initially with ventilation tubes and later with hearing aids. Prevention of secondary complications: Potential pre- and postoperative anesthetic concerns secondary to spine anomalies and difficult airway management need to be anticipated. All affected individuals should receive influenza and pneumococcal immunizations as well as routine immunizations. Bacterial endocarditis prophylaxis is recommended for those with a prosthetic cardiac valve, prosthetic material used for cardiac valve repair, or previous infective endocarditis. Surveillance: For those on ERT: physical examination at least every six months; annual assessment of quality of life parameters and pulmonary function tests. For all individuals: annual endurance tests to evaluate functional status of the cardiovascular, pulmonary, musculoskeletal, and nervous systems; annual assessment of upper and lower extremities for functionality and malalignment, hips for dysplasia/subluxation and thoracolumbar spine for kyphosis; neurologic examination and cervical spine radiographs every six months to assess for spinal cord compression; yearly whole-spine MRI with flexion-extension views every one to three years. Perform annual evaluation of heart rate with electrocardiogram and echocardiogram every one to three years depending on disease course. Annual assessment for obstructive sleep apnea and pulmonary function; monitor nutritional status using MPS IVA-specific growth charts. Perform vision and eye exam at every visit, dental evaluation every six to 12 months, and annual audiogram. Agents/circumstances to avoid: Excessive weight gain; beta blockers.

GENETIC COUNSELING:

MPS IVA is inherited in an autosomal recessive manner. At conception, each sib of an affected individual has a 25% chance of being affected, a 50% chance of being an asymptomatic carrier, and a 25% chance of being unaffected and not a carrier. Carrier testing for at-risk family members and prenatal testing for pregnancies at increased risk are possible if the pathogenic variants in the family have been identified.

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