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Pseudo Hurler Polydystrophy

Synonyms of Pseudo Hurler Polydystrophy

  • ML III alpha/beta
  • mucolipidosis IIIA
  • mucolipidosis III alpha/beta

Disorder Subdivisions

  • mucolipidosis III alpha/beta

General Discussion

Pseudo-Hurler polydystrophy (mucolipidosis type III) is a rare genetic metabolic disorder characterized by a defective enzyme known as UPD-N-acetylglucosamine-1-phosphotransferase. This defective enzyme ultimately results in the accumulation of certain complex carbohydrates (mucopolysaccharides) and fatty substances (mucolipids) in various tissues of the body. The symptoms of this disorder are similar, but less severe than those of I-cell disease (mucolipidosis type II) and may include progressive joint stiffness, curvature of the spine (scoliosis), and/or skeletal deformities of the hands (e.g., claw-hands). Growth delays accompanied by deterioration of the hip joints typically develop in children with pseudo-Hurler polydystrophy. Additional symptoms may include clouding of the corneas of the eyes, mild to moderate coarseness of facial features, mild mental retardation, easy fatigability, and/or heart disease. Pseudo-Hurler polydystrophy is inherited as an autosomal recessive trait.

This disorder belongs to a group of diseases known as lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that break down certain fats and carbohydrates. Defective lysosomal enzymes associated with pseudo-Hurler polydystrophy leads to the accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells of many tissues of the body.


In most cases, children with pseudo-Hurler polydystrophy do not exhibit symptoms until 2-4 years of age. Specific symptoms and rate of progression may vary from case to case although the disorder is often slowly progressive.

Initial symptoms may include stiffness of the hands and shoulders. In some cases, claw-like deformities of the hands may occur. These symptoms may progress to cause difficulty with specific tasks (e.g., getting dressed). Eventually, carpal tunnel syndrome may develop. Carpal tunnel syndrome is a neurological disorder characterized by compression of the median nerve, which passes through the carpal tunnel inside the wrist (peripheral nerve entrapment). Symptoms of this disorder affect the hand and wrist and may include pain, numbness, loss of feeling in the fingertips, and/or unusual sensation such as burning or "pins and needles."

Additional symptoms associated with pseudo-Hurler polydystrophy may include side-to-side curvature of the spine (scoliosis), degeneration of the hip, joints that are permanently fixed in a bent or flexed position (contractures), and short stature. Progressive degeneration of the hip and joint contractures may cause difficulty walking or force affected individuals to walk with a characteristic waddling gait.

Affected children may also develop coarse facial features, clouding (opacity) of the surface of the eye (cornea), abnormalities affecting the nerve-rich membrane (retina) lining the eyes (mild retinopathy), and irregular curvature of the cornea (hyperopic astigmatism).

Although many children with pseudo-Hurler polydystrophy have normal intelligence, some may develop mild mental retardation or learning disabilities. In some cases, affected children develop aortic insufficiency, a cardiovascular condition in which the aortic valve weakens preventing the valve from shutting and allowing backflow of blood from the major artery of the body (aorta) into one of the chambers of the heart (left ventricle). Symptoms of aortic insufficiency may include palpitations, fatigue, shortness of breath, and chest pain.


Pseudo-Hurler polydystrophy is inherited as an autosomal recessive trait. Genetic diseases are determined by two genes, one received from the father and one from the mother.

Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%.

Investigators have determined that pseudo-Hurler polydystrophy is caused by disruption or changes (mutations) in the UDP-N-acetylglucosamine-1-phosphotransferase gene known as GNPTAB located on the long arm of chromosome 4 (4q21-q23). Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Pairs of human chromosomes are numbered from 1 through 22, and an additional 23rd pair of sex chromosomes which include one X and one Y chromosome in males and two X chromosomes in females. Each chromosome has a short arm designated "p" and a long arm designated "q". Chromosomes are further sub-divided into many bands that are numbered. For example, "chromosome 4q21-q23" refers to bands 21-23 on the long arm of chromosome 4. The numbered bands specify the location of the thousands of genes that are present on each chromosome.

Investigators have determined that variant pseudo-Hurler polydystrophy (mucolipidosis IIIC) results from mutations in the GlcNAc-phosphotransferase -subunit gene located on chromosome 16.

The symptoms of pseudo-Hurler polydystrophy result from a defective enzyme known as UPD-N-acetylglucosamine-1-phosphotransferase. Due to this defect, certain lysosomal enzymes fail to reach their proper destination (i.e., lysosomes). Lysosomes are particles bound in membranes within cells that break down certain fats and carbohydrates. Lysosomal enzymes are mistakenly secreted outside cells resulting in elevated lysosomal enzymes in the serum and fluids of affected individuals. The failure of lysosomal enzymes to reach the lysosomes within cells results in the accumulation of certain fatty substances (mucolipids) and certain complex carbohydrates (mucopolysaccharides) within the cells, which, in turn, results in the symptoms of the disorder.

Affected Populations

Pseudo-Hurler polydystrophy affects males and females in equal numbers. The prevalence of the disorder is unknown. Pseudo-Hurler polydystrophy is often misdiagnosed making it difficult to determine its true frequency in the general population. One estimate places the frequency at 1 in 1 million births.

As a group, lysosomal storage diseases are believed to have an estimated frequency of about one in every 5,000 live births. Although the individual diseases are rare, the group together affects many people around the world.

Related Disorders

Symptoms of the following disorders can be similar to those of pseudo-Hurler polydystrophy. Comparisons may be useful for a differential diagnosis:

Hurler syndrome (mucopolysaccharidosis type 1-H; MPS 1-H) is the most severe form of mucopolysaccharidosis. It is characterized by a deficiency of the enzyme alpha-L-iduronidase, which results in an accumulation of dermatan and heparan sulfates. Symptoms of the disorder first become evident at six months to two years of age. Affected infants may experience developmental delays, recurrent urinary and upper respiratory tract infections, noisy breathing and persistent nasal discharge. Additional physical problems may include clouding of the cornea of the eye, an unusually large tongue, severe deformity of the spine, and joint stiffness. Mental development begins to regress at about the age of two. (For more information on this disorder, choose "Hurler" as your search term in the Rare Disease Database.)

Maroteaux-Lamy syndrome (mucopolysaccharidosis type VI; MPS VI) is characterized by a deficiency of the enzyme N-acetylgalactosamine-4-sulfatase. This form of MPS varies greatly among affected individuals. Some affected individuals only experience a few mild symptoms, other develop a more severe form of the disorder. Possible symptoms of Maroteaux-Lamy syndrome include coarse facial features, umbilical hernia, a prominent breastbone (pectus carinatum), joint contractures, clouding of the corneas, and abnormal enlargement of the liver and/or spleen (heptasplenomegaly). Skeletal malformations and heart disease may occur in individuals with this form of MPS. In most cases, intelligence is normal. (For more information on this disorder, choose "Maroteaux-Lamy" as your search term in the Rare Disease Database.)

Hunter syndrome, also known as mucopolysaccharidosis II, is a rare inborn error of metabolism characterized by deficiency of an enzyme known as iduronate sulfatase. In individuals with Hunter syndrome, deficiency or improper functioning of this lysosomal enzymes leads to an abnormal accumulation of certain complex carbohydrates (glycosaminoglycans [mucopolysaccharides]) in cells within various bodily tissues, such as the skeleton, joints, brain, spinal cord, heart, spleen, or liver. Initial symptoms and findings associated with Hunter syndrome usually become apparent between ages two to four years. Such abnormalities may include progressive growth delays, resulting in short stature; joint stiffness, with associated restriction of movements; and coarsening of facial features, including thickening of the lips, tongue, and nostrils. Affected children may also have an abnormally large head (macrocephaly), a short neck and broad chest, delayed tooth eruption, progressive hearing loss, and enlargement of the liver and spleen (hepatosplenomegaly). Hunter syndrome is inherited as an X-linked recessive trait. (For more information on this disorder, choose "Hunter" as your search term in the Rare Disease Database.)

Lysosomal storage diseases are inherited metabolic diseases that are characterized by an abnormal build-up of various toxic materials in the body's cells as a result of enzyme deficiencies. There are nearly 50 of these disorders altogether, and they may affect different parts of the body, including the skeleton, brain, skin, heart, and central nervous system. New lysosomal storage disorders continue to be identified. While clinical trials are in progress on possible treatments for some of these diseases, there is currently no approved treatment for many lysosomal storage diseases. (For more information on this disorder, choose "lysosomal storage diseases" as your search term in the Rare Disease Database.)

Standard Therapies

A diagnosis of pseudo-Hurler polydystrophy may be suspected based upon a thorough clinical evaluation, a detailed patient history and identification of characteristic findings. A variety of specialized tests may confirm a diagnosis. These tests include detecting elevated lysosomal enzyme activity in serum or decreased enzyme levels in white blood cells or cultured connective tissue cells (fibroblasts).

There is no definitive treatment for pseudo-Hurler polydystrophy. Treatment is directed toward the specific symptoms that are apparent in each individual. Treatment may require the coordinated efforts of a team of specialists. Pediatricians, orthopedic surgeons, cardiologists, eye specialists, and other healthcare professionals may need to systematically and comprehensively plan an affected child's treatment.

Surgery may be used to treat a variety of symptoms associated with pseudo-Hurler polydystrophy including carpal tunnel syndrome, skeletal malformations, and degeneration of the hip. Corneal transplantation has been performed with mixed results. Physical therapy and exercise may improve joint stiffness. Heart valve replacement may be necessary in some cases.

Genetic counseling may be of benefit for affected individuals and their families. Other treatment is symptomatic and supportive.

Investigational Therapies

Researchers are studying biphosphonate therapy such as pamidronate for the treatment of individuals with pseudo-Hurler polydystrophy. Initial studies have demonstrated improvement of symptoms in some individuals with pseudo-Hurler syndrome. More research is necessary to determine the long-term safety and effectiveness of biphosphonate therapy for individuals with pseudo-Hurler-polydystrophy.

Information on current clinical trials is posted on the Internet at All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010

For information about clinical trials sponsored by private sources, contact:

Pseudo Hurler Polydystrophy Resources

Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder.

NORD Member Organizations:

(To become a member of NORD, an organization must meet established criteria and be approved by the NORD Board of Directors. If you're interested in becoming a member, please contact Susan Olivo, Membership Manager, at

Other Organizations:


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Haddad FS, Hill RA, Vellodi A. Orthopaedic manifestations of mucolipidosis III: an illustrative case. J Pediatr Orthop B. 2000;9:58-61.

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McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:252600; Last Update:3/30/2005. Available at: Accessed on: 3/30/2005.

McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No:252605; Last Update:5/30/2003. Available at: Accessed on: 3/30/2005.

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Report last updated: 2008/05/25 00:00:00 GMT+0

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