- Donate
- Understanding Rare Disease
- Living with a Rare Disease
- Community Support
- Advancing Research
- Driving Policy
- Get Involved
- Rare Disease News
- Resource Library
- About Us
- For Clinicians & Researchers
- For Patient Organizations
Last updated: August 03, 2016
Years published: 1997, 2002, 2007, 2008, 2012, 2016
NORD gratefully acknowledges Claude Abdallah, MD, MSc, Department of Anesthesiology, Childrenโs National Medical Center, Assistant Professor of Anesthesiology and Pediatrics, The George Washington University Medical Center, for assistance in the preparation of this report.
Summary
Fucosidosis is a rare genetic disorder characterized by deficiency of the enzyme alpha-L-fucosidase, which is required to break down (metabolize) certain complex compounds (e.g., fucose-containing glycolipids or fucose-containing glycoproteins). Fucose is a type of the sugar required by the body to perform certain functions (essential sugar). The inability to breakdown fucose-containing compounds results in their accumulation in various tissues in the body. Fucosidosis results in progressive neurological deterioration, skin abnormalities, growth retardation, skeletal disease and coarsening of facial features. The symptoms and severity of fucosidosis are highly variable and the disorder represents a disease spectrum in which individuals with mild cases have been known to live into the third or fourth decades. Individuals with severe cases of fucosidosis can develop life-threatening complications early in childhood.
Introduction
The disorder belongs to a group of diseases known as lysosomal storage disorders. Lysosomes are particles bound in membranes within cells that function as the primary digestive units within cells. Enzymes within lysosomes break down or digest particular nutrients, such as certain fats and carbohydrates. Low levels or inactivity of the alpha-L-fucosidase enzyme leads to the abnormal accumulation of fucose-containing compounds in the tissues of individuals with fucosidosis.
The symptoms of fucosidosis vary greatly even among individuals within the same family. Fucosidosis can be rapidly progressive causing severe, life-threatening complications in children or develop during adolescence and progress more slowly eventually causing serious complications in adulthood. In the past, fucosidosis was sometimes separated in type I and type II. However, researchers now believe that fucosidosis represents a disease spectrum with a wide variety of expression. Cases labeled fucosidosis type I (early onset, rapid progression) represent the severe end of the spectrum and those labeled fucosidosis type II represent the mild end.
Infants with severe forms of fucosidosis may not exhibit any symptoms until 6 months to one year of life. Initial symptoms may be associated with mental and motor deterioration such as delayed acquisition of skills required to coordinate mental and muscular activities (psychomotor retardation). Physicals findings may also develop including coarse facial features, thickened lips and tongue, multiple deformities of the bone (mild dysostosis multiplex), loss of muscle tone (hypotonia) resulting in โfloppinessโ and growth retardation. Progressive neurological deterioration may result in a variety of symptoms including intellectual disability, various movement disorders and/or uncontrolled rigid extensions and rotations of the arms, legs, fingers, and toes (decerebrate rigidity). Severe fucosidosis often progresses to cause life-threatening neurodegenerative complications and/or severe, progressive loss of weight and muscle mass (cachexia), usually within the first few years of life.
Less common findings associated with severe forms of fucosidosis include abnormally enlarged internal organs (visceromegaly), such as the liver and spleen (hepatosplenomegaly) or heart (cardiomegaly), seizures, hearing loss, abnormal curvature of the spine (kyphoscoliosis), and repeated respiratory infections. Some affeced individuals may sweat excessively and their sweat may contain abnormally high levels of salt.
In some less severe cases, the symptoms associated progressive deterioration of the central nervous system may not become obvious until the age of 18 months to three years. The symptoms of less severe forms of fucosidosis are similar to the more severe forms, but tend to be milder with slower progression. Affected individuals may develop wart-like growths (angiokeratomas) on the skin around the age of two years. These lesions occur mainly on the abdomen, buttocks, thighs, and/or external genitalia. Some individuals may experience fixation of certain joints in a permanently flexed position (contractures), involuntary muscle spasms (spasticity) that result in slow, stiff movements of the legs and inadequate ability to sweat (anhidrosis). Individuals with less severe forms of fucosidosis may live well into their second, third or fourth decades before the disorder progresses to cause life-threatening complications.
Fucosidosis is caused by disruptions or changes (mutations) of the alpha-L-fucosidase (FUCA1) gene resulting in deficiency of the alpha-L-fucosidase enzyme. The symptoms of fucosidosis occur as a result of excessive accumulation of fucose-containing compounds (e.g., certain glycosphingolipids or certain glycoproteins) in the body due to abnormally low levels of this enzyme. Researchers do not know why the symptoms and severity vary so greatly in individuals with fucosidosis. Some researchers believe that mutation of the FUCA1 gene in combination with certain genetic and environmental factors all play a role in the severity of the disease in individuals. More research is necessary to determine what these factors may be.
Individuals with fucosidosis also have a pseudogene- a gene that can no longer creates proteins or is no longer expressed in the body. The pseudogene associated with fucosidosis is called FUCA1P.
Fucosidosis is inherited as an autosomal recessive trait. Recessive genetic disorders occur when an individual inherits two copies of an abnormal gene for the same trait, one from each parent. If an individual inherits 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 altered gene and 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 is 25%. The risk is the same for males and females.
Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Fucosidosis affects males and females in equal numbers. Fewer than 100 cases have been reported in the medical literature. One estimate place the incidence rates at below 1 in 200,000 live births. Some researchers believe fucosidosis is underdiagnosed making it difficult to determine its true frequency in the general population.
Although rare, fucosidosis has been identified in more than 20 countries across North and South America, Europe, Asia and Africa, with many patients found in the southwestern United States and southern Italy. As a group, the lysosomal storage diseases are believed to have an estimated frequency of about one in every 5,000 live births.
A diagnosis of fucosidosis may be suspected in infants with skeletal disease during the first year of life that is accompanied by neurological deterioration and intellectual disability. The diagnosis may be confirmed thorough clinical evaluation, detailed patient history, and a variety of specialized tests. For example, electron microscopic examination of tissue samples from the skin, liver, spleen, heart, lung, kidney, sweat glands, and/or other cells may reveal abnormal โcavitiesโ (vacuoles) inside these cells. These vacuoles may be clear or filled with sand-like granules or thin, disc-like (lamellar) bodies. Advanced imaging techniques, such as magnetic resonance imaging (MRI) and computer-assisted tomography (CT scan) of the brain may confirm degeneration of the white matter of the brain. Laboratory analysis of urinary samples may reveal increased levels of certain fucose-containing complex compounds in the urine (e.g., oligosacchariduria and glycopeptiduria). In addition, reduced activity of the alpha-L-fucosidase enzyme may be confirmed by enzyme tests (assays) on cultured fibroblasts and leukocytes. (As some unaffected individuals may normally show reduced levels of alpha-L-fucosidase in the serum and plasma, assays conducted on the serum and plasma alone may not be conclusive; therefore, fibroblast and leukocyte assay testing is necessary.)
Fucosidosis has been successfully diagnosed before birth (prenatally) through the use of specialized tests such as chorionic villus sampling (CVS) and/or amniocentesis. During CVS, fetal tissue samples are removed and enzyme tests (assays) are performed on cultured tissue cells (fibroblasts) and/or white blood cells (leukocytes). During amniocentesis, a sample of fluid that surrounds the developing fetus is removed and studied.
Treatment
The treatment of fucosidosis is directed toward the specific symptoms that are apparent in each individual. For example, antibiotic therapy may be administered to treat recurrent respiratory infections or fluid replacement may be considered to counter the effects of dehydration that may occur due to excessive sweating. A team approach for individuals with fucosidosis may be necessary and may include special social support and other medical services. Genetic counseling is recommended for affected individuals and their families.
Some individuals with fucosidosis have been treated with bone marrow transplantation. In two separate cases reported in the medical literature, younger siblings with fucosidosis who were treated early showed considerable improvement in symptoms following a bone marrow transplant from an unrelated donor (allogeneic bone marrow transplant). In both cases, older, untreated siblings showed significantly worse clinical outcome. Research in bone marrow transplant for fucosidosis and related lysosomal diseases is ongoing. Many reports in the literature detail that deficient enzyme activity is boosted in individuals receiving a transplant. More research is necessary to determine the long-term safety and effectiveness of bone marrow transplants for individuals with fucosidosis.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov . 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:
Toll -free: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clincialtrialsregister.eu/
(Please note that some of these organizations may provide information concerning certain conditions potentially associated with this disorder [e.g., intellectual disability etc.].)
TEXTBOOKS
Grabowski GA. Fucosidosis. NORD Guide to Rare Disorders. Philadelphia, PA: Lippincott Williams & Wilkins; 2003:445-6.
Rimoin D, Connor JM, Pyeritz RP, Korf BR. Eds. Emory and Rimoinโs Principles and Practice of Medical Genetics. 4th ed. New York, NY: Churchill Livingstone; 2002:2690-2.
Scriver CR, Beaudet AL, Sly WS, et al. Eds. The Metabolic Molecular Basis of Inherited Disease. 8th ed. New York, NY: McGraw-Hill Companies; 2001:3507-4.
Lyon G, Adams RD, Kolodny EH. Eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. New York, NY: McGraw-Hill Companies; 1996:167-9.
JOURNAL ARTICLES
Miano M, Lanino E, Gatti R, et al., Four year follow-up of a case of fucosidosis treated with unrelated donor bone marrow transplantation. Bone Marrow Transplant. 2001;27:747-51.
Willems PJ, Seo HC, Coucke P, Tonlorenzi R, OโBrien JS. Spectrum of mutations in fucosidosis. Eur J Hum Genet. 1999;7:60-7.
Krivit W, Peters C, Shapiro EG. Bone marrow transplantation as effective treatment of central nervous system disease in globoid cell leukodystrophy, metachromatic leukodystrophy, adrenoleukodystrophy, mannosidosis, fucosidosis, aspartylglucosaminuria, Hurler, Maroteaux-Lamy, and Sly syndromes, and Gaucher disease type III. Curr Opin Neurol. 1999;12:167-76.
Vellodi A, Cragg H, Winchester B, et al., Allogeneic bone marrow transplantation for fucosidosis. Bone Marrow Transplant. 1995;15:153-8.
Provenzale JM, Barboriak DP, Sims K. Neuroradiologic findings in fucosidosis, a rare lysosomal storage disease. Am J Neuroradiol. 1995;16:809-13.
Tiberio G, Filocamo M, Gatti R, Durand P. Mutations in fucosidosis gene: a review. Acta Genet Med Gemllol (Roma). 1995;44:223-32.
Willems PJ, Gatti R, Darby JK, et al., Fucosidosis revisited: a review of 77 patients. Am J Med Genet. 1991;38:111-31.
INTERNET
Kruer MC, Steiner RD. Lysosomal Storage Disease.Medscape. Last Update December 9, 2015. https://emedicine.medscape.com/article/1182830-overview . Accessed August 2, 2016.
Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Fucosidosis. Entry No: 230000. Last update 03/04/2015. Available at: https://omim.org/entry/230000 Accessed August 2, 2016
Froissart R, Marie I. Fucosidosis. Orphanet encyclopedia. Last Update September 2015. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=349. Accessed August 2, 2016
NORD strives to open new assistance programs as funding allows. If we donโt have a program for you now, please continue to check back with us.
NORD and MedicAlert Foundation have teamed up on a new program to provide protection to rare disease patients in emergency situations.
Learn more https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Ensuring that patients and caregivers are armed with the tools they need to live their best lives while managing their rare condition is a vital part of NORDโs mission.
Learn more https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/This first-of-its-kind assistance program is designed for caregivers of a child or adult diagnosed with a rare disorder.
Learn more https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
View report