Pseudo Hurler Polydystrophy

National Organization for Rare Disorders, Inc.

Skip to the navigation


It is possible that the main title of the report Pseudo Hurler Polydystrophy is not the name you expected. Please check the synonyms listing to find the alternate name(s) and disorder subdivision(s) covered by this report.


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

Disorder Subdivisions

  • None

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.

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:



Muenzer J, Wedehase B. Mucolipidosis II and III. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:472-3.

Scriver CR, et al., eds. The Metabolic and Molecular Basis of Inherited Disease. 7th Ed. New York, NY; McGraw-Hill Companies, Inc; 1995:3469-80.

Lyon G, et al., eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. New York, NY: McGraw-Hill Companies; 1996:164-5.

Adams, RD, et al., eds. Principles of Neurology. 6th ed. New York, NY: McGraw-Hill, Companies; 1997:942.


Steet RA, Hullin R, Kudo M, et al. A splicing mutation in the alpha/beta GlcNAc-1-phosphotransferase gene results in an adult onset form of mucolipidosis III associated with sensory neuropathy and cardiomyopathy. Am J Med Genet. 2005;132:369-75.

Robinson C, Baker N, Noble J, et al. The osteodystrophy of mucolipidosis type III and the effects of intravenous pamidronate treatment. J Inherit Metab Dis. 2002;25:681-93.

Pourjavan S, Fryns JP, Van Hove JL, Poorthuis BJ, Casteels I. Ophthalmological findings in a patient with mucolipidosis III (pseudo-Hurler polydystrophy). A case report. Bull Soc Belge Ophthalmol. 2002;19-24.

Tylki-Szymanska A, Czartoryska B, Groener JE, Lugowska A. Clinical variability in mucolipidosis III (pseudo-Hurler polydystrophy). Am J Med Genet. 2002;15:214-8.

Raas-Rothschild A, Cormier-Daire V, Bao M, et al. Molecular basis of variant pseudo-Hurler polydystrophy (mucolipidosis IIIC). J Clin Invest. 2000;105:673-81.

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

Hetherington C, Harris NJ, Smith TW. Orthopaedic management in four cases of mucolipidosis type III. J R Soc Med. 1999;92:244-6.

Haddad FS, Jones DH, Vellodi A, Kane N, Pitt MC. Carpal tunnel syndrome in the mucopolysaccharidoses and mucolipidoses. J Bone Joint Surg Br. 1997;79:576-82.

Umehara F, Matsumoto W, Kuriyama M, Sukegawa K, Gasa S, Osame M. Mucolipidosis III (pseudo-Hurler polydystrophy); clinical studies in aged patients in one family. J Neurol Sci. 1997;146:167-72.


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.


CLIMB (Children Living with Inherited Metabolic Diseases)

Climb Building

176 Nantwich Road

Crewe, CW2 6BG

United Kingdom

Tel: 4408452412173

Fax: 4408452412174



Vaincre Les Maladies Lysosomales

2 Ter Avenue

Massy, 91300


Tel: 0169754030

Fax: 0160111583



The Arc

1825 K Street NW, Suite 1200

Washington, DC 20006

Tel: (202)534-3700

Fax: (202)534-3731

Tel: (800)433-5255

TDD: (817)277-0553



NIH/National Institute of Diabetes, Digestive & Kidney Diseases

Office of Communications & Public Liaison

Bldg 31, Rm 9A06

31 Center Drive, MSC 2560

Bethesda, MD 20892-2560

Tel: (301)496-3583



Society for Mucopolysaccharide Diseases

MPS House

Repton Place

White Lion Road


Buckinghamshire, HP7 9LP

United Kingdom

Tel: 08453899901

Fax: 08453899902



Canadian Society for Mucopolysaccharide and Related Diseases, Inc.

PO Box 30034

RPO Parkgate

North Vancouver

British Columbia, V7H 2Y8


Tel: 6049245130

Fax: 6049245131

Tel: 8006671846



International Advocate For Glycoprotein Storage Diseases

20880 Canyon View Drive

Saratoga, CA 95070




Genetic and Rare Diseases (GARD) Information Center

PO Box 8126

Gaithersburg, MD 20898-8126

Tel: (301)251-4925

Fax: (301)251-4911

Tel: (888)205-2311

TDD: (888)205-3223


Hide & Seek Foundation for Lysosomal Disease Research

6475 East Pacific Coast Highway Suite 466

Long Beach, CA 90803

Tel: (877)621-1122

Fax: (866)215-8850



For a Complete Report

This is an abstract of a report from the National Organization for Rare Disorders, Inc.® (NORD). Cigna members can access the complete report by logging into For non-Cigna members, a copy of the complete report can be obtained for a small fee by visiting the NORD website. The complete report contains additional information including symptoms, causes, affected population, related disorders, standard and investigational treatments (if available), and references from medical literature. For a full-text version of this topic, see