Mucopolysaccharidosis

Mucopolysaccharidosis

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Mucopolysaccharidosis (MPS) involves defective activity of the lysosomal enzymes, which blocks degradation of mucopolysaccharides and leads to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate. MPS can be subclassified as follows:

The image below depicts Morquio syndrome.

Patients with MPS have normal development initially, with abnormalities appearing in infancy or later in childhood. Those with multiple organ system involvement may have the following presentations:

Findings from examination may include the following:

See Presentation for more detail.

Prenatal screening studies that may be useful include the following:

Postnatal diagnostic studies that may be helpful include the following:

Imaging studies that may be warranted are as follows:

Other tests to be considered are as follows:

See Workup for more detail.

Specific treatment or cure is limited for MPS. Management has been limited to supportive care and experimental treatment modalities. Medical treatment modalities include the following:

Surgical care for specific conditions may include the following:

Multispecialty care is mandatory for these patients and should include a pediatrician (internist), a neurologist, a cardiologist, an ophthalmologist, an audiologist, an orthopedic surgeon, and a physical and occupational therapist.

See Treatment and Medication for more detail.

Mucopolysaccharides consist of glycosaminoglycans (GAGs) attached to a link protein with a hyaluronic acid core. Lysosomal enzymes degrade these macromolecules into smaller components. Mucopolysaccharidosis (MPS) involves defective activity of these enzymes, which blocks degradation of mucopolysaccharides. This incomplete degradation process leads to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate, and the abnormal accumulation of these compunds interferes with cell function.

Different forms of MPS were described separately throughout the 20th century. Their clinical presentations vary, depending on the type of enzyme defect and the glycoprotein accumulated. (See Lysosomal Storage Disease and Madelung Deformity.)

Defective activity of the lysosomal enzymes blocks the degradation process of mucopolysaccharides, leading to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate. These degradation by-products are then secreted and detected in the urine. MPS can be subclassified according to the type and amount of substance that accumulates, as follows [1, 2, 3] :

Defective activity of the lysosomal enzymes blocks the degradation process of mucopolysaccharides, leading to abnormal accumulation of heparan sulfate, dermatan sulfate, and keratan sulfate.

All forms of MPS are inherited as autosomal recessive disorders, with the exception of Hunter syndrome (MPS II), which is inherited as a sex-linked recessive disorder.

Worldwide, the prevalence of all types of MPS is 1 case in 16,000-30,000 births. MPS III accounts for 80% of cases.

The ages at which features of MPS present are somewhat variable. MPS features mostly present in the first few months of life. However, Morquio syndrome usually presents in children aged 2-4 years, and MPS IS and MPS VI can present late in childhood.

All mucopolysaccharidoses are inherited as autosomal recessive disorders, with the exception of Hunter syndrome (MPS II); thus, all patients with Hunter syndrome are males.

These syndromes are found in all ethnic groups. The incidence of MPS II is higher in Israeli Jews, and the incidence of MPS IV is increased in French Canadians.

The prognosis varies, depending on the type of MPS. Most of these patients have shortened life spans, and some die in infancy. These disease processes have significant effects on the growth and development of the musculoskeletal system, including joint stiffness or hyperlaxity, deformities, and progressive loss of function. Multiple other organ systems are involved. The type and extent of organ system involvement are variable, depending on the subset of the disease.

Bone marrow transplantation has some positive effects systemically, such as reduction in hepatosplenomegaly, airway obstruction, and cardiopulmonary disease. These effects have resulted in improved life span, and many of these patients survive beyond the first decade of life.

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Tarek Bittar, MD Staff Physician, Department of Orthopedic Surgery, Martin Luther King Medical Center

Tarek Bittar, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons

Disclosure: Nothing to disclose.

Eleby R Washington, III, MD, FACS Associate Professor, Department of Surgery, Division of Orthopedics, Charles R Drew University of Medicine and Science

Eleby R Washington, III, MD, FACS is a member of the following medical societies: American Academy of Orthopaedic Surgeons, American College of Surgeons, American Medical Association, International College of Surgeons, National Medical Association

Disclosure: Nothing to disclose.

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

George H Thompson, MD Director of Pediatric Orthopedic Surgery, Rainbow Babies and Children’s Hospital, University Hospitals Case Medical Center, and MetroHealth Medical Center; Professor of Orthopedic Surgery and Pediatrics, Case Western Reserve University School of Medicine

George H Thompson, MD is a member of the following medical societies: American Orthopaedic Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Academy of Orthopaedic Surgeons

Disclosure: Received none from OrthoPediatrics for consulting; Received salary from Journal of Pediatric Orthopaedics for management position; Received none from SpineForm for consulting; Received none from SICOT for board membership.

Jeffrey D Thomson, MD Professor of Orthopedic Surgery, University of Connecticut School of Medicine; Director of Orthopedic Surgery, Connecticut Children’s Medical Center; Vice President of Medical Staff, Connecticut Children’s Medical Center

Jeffrey D Thomson, MD is a member of the following medical societies: American Academy of Orthopaedic Surgeons, Pediatric Orthopaedic Society of North America, Scoliosis Research Society

Disclosure: Nothing to disclose.

Charles T Mehlman, DO, MPH Professor of Pediatrics and Pediatric Orthopedic Surgery, Division of Pediatric Orthopedic Surgery, Director, Musculoskeletal Outcomes Research, Cincinnati Children’s Hospital Medical Center

Charles T Mehlman, DO, MPH is a member of the following medical societies: American Academy of Pediatrics, American Fracture Association, Scoliosis Research Society, Pediatric Orthopaedic Society of North America, American Medical Association, American Orthopaedic Foot and Ankle Society, American Osteopathic Association, Arthroscopy Association of North America, North American Spine Society, Ohio State Medical Association

Disclosure: Nothing to disclose.

Mucopolysaccharidosis

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