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Fucosidosis

Alpha-L-Fucosidase Deficiency

Fucosidosis a glycoprotein storage disorder and involves genetic mutations of the FUCA1 gene, which, in turn, profoundly inhibits the functionality of the alpha-L-fucosidase enzyme, responsible for cleaving the fucose sugar molecule at the end of the catabolism process.


Presentation

Fucosidosis is a disorder that may have a variable presentation even in individuals belonging to one family. Even though the symptoms elicited remain the same, patients may be affected by fucosidosis with an early onset and rapid progression, or a disease that is diagnosed during adolescence and progresses slowly with less profound symptoms.

The most severe type of fucosidosis tends to initially manifest at a time between the 6th month to the 1st year of an infant's life. Symptoms include psychomotor retardation, namely the slowing-down of emotional and physical reactions to various stimuli. Other findings that may be revealed in a physical examination may include [1]:

Fucosidosis primarily leads to a neurodegeneration due to central nervous system myelin loss. This is evident by means of mental retardation, loss of coordination, and rigidity of the extremities that involves extension and rotation (decerebrate rigidity) [2] [3] [4]. As the disease progresses, the loss of weight and muscle mass sustained may constitute life-threatening sequelae that can lead to a patient's demise even within the first years of life.

Other signs related to fucosidosis include visceromegaly that can affect the spleen, liver, and heart, epilepsy, hearing impairment or total hearing loss, kyphoscoliosis, and persistent respiratory infections. Hyperhidrosis is another potential symptom.

Symptoms are identical in less severe as well as more severe forms of Fucosidosis. However, they may be milder and may progress more slowly in the less severe forms. Angiokeratomas usually form on the skin at the age of approximately 2 years and are primarily found on the abdomen, thighs, and genital areas. Contractures, spasticity, and anhidrosis may also complicate the clinical picture.

Splenomegaly
  • If types are used, the symptoms are usually classified as: Type I (also called severe) begins in the first 3-18 months of life coarse facial features enlarged liver (hepatomegaly), spleen (splenomegaly), and/or heart (cardiomegaly) abnormal bone formation[dermaamin.com]
  • […] eventual dementia progressive motor deterioration: initially hypotonia before spasticity manifests coarse facies dwarfism and other muscoskeletal anomalies recurrent respiratory infections angiokeratomas organomegaly : glossomegaly , hepatomegaly , splenomegaly[radiopaedia.org]
  • Clincal signs and symptoms include hepatomegaly, splenomegaly, hearing loss, mental retardation, skeletal abnormalities, and recurrent respiratory infections.[icd10data.com]
Coarse Facial Features
  • Fucosidosis is a rare autosomal recessive lysosomal storage disease with the main clinical findings of progressive neuromotor deterioration, seizures, coarse facial features, dysostosis multiplex, angiokeratoma corporis diffusum, visceromegaly, recurrent[ncbi.nlm.nih.gov]
  • facial features, growth retardation, and recurrent sinopulmonary infections, as well as seizures, visceromegaly, angiokeratoma and dysostosis.[orpha.net]
  • Its clinical phenotypes include progressive neurological and mental deterioration, coarse facial features, growth retardation, visceromegaly, angiokeratomas, and seizures.[ncbi.nlm.nih.gov]
  • At age 12, he could not walk without help; he was admitted to the hospital with intellectual disability, short stature and coarse facial features. A skeletal survey showed dysostosis multiplex.[ncbi.nlm.nih.gov]
  • Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, hepatomegaly, and dysostosis multiplex.[omicsonline.org]
Italian
  • This mutation was present in one allele and was found also in the mother who was of Italian origin. (2) A C to A mutation (W382X) in exon 6 in an Italian patient.[ncbi.nlm.nih.gov]
  • This G60D mutation creates a unique site for AflIII. 4) A frameshift mutation resulted from a two-base deletion in exon 2 (K151fs) in an Italian patient.[ncbi.nlm.nih.gov]
  • In Italian patients, only seven mutations have been described and P141fs and G60D mutations are present in more than 50% of the cases. The P141fs mutation is absent in other ethnic groups.[ncbi.nlm.nih.gov]
  • Abstract A random sample of unrelated students living in Grotteria and Mammola, two villages of Southern Italy from where most of the Italian patients affected with fucosidosis originate, was analyzed for seven red cell enzyme polymorphisms and seven[ncbi.nlm.nih.gov]
Progressive Mental Retardation
  • Historical note and terminology Fucosidosis is a progressive mental retardation syndrome involving lysosomal storage that was first described by Durand in 1966 ( Durand et al 1966 ; Durand et al 1969 ) and involves both fuco-oligosaccharide and fuco-glycosphingolipid[medlink.com]
  • The more severe (infantile or type I) phenotype includes rapidly progressive mental retardation, hepatosplenomegaly, severe dysostosis multiplex, and often death between 3 and 12 years of age.[ommbid.mhmedical.com]
  • As the disease progresses, more serious and ever worsening symptoms develop, including seizures, spastic quadriplegia, progressive mental retardation and chronic lung infections.[disability-benefits-help.org]
Short Stature
  • At age 12, he could not walk without help; he was admitted to the hospital with intellectual disability, short stature and coarse facial features. A skeletal survey showed dysostosis multiplex.[ncbi.nlm.nih.gov]
  • The clinical examination revealed short stature, coarse facial features, bilateral ptosis, hypertonic lower extremities, psychomotor retardation and asthma.[omicsonline.org]
  • Bone cells are involved which can result in short stature, coarse facial features, and prominent eyes. Seizures have been reported. The liver and spleen are often enlarged but cells of the kidney and pancreas are involved as well.[disorders.eyes.arizona.edu]
Weight Loss
  • Signs can include loss of learned behavior, change in temperament, blindness, loss of balance, deafness and weight loss.[vetgen.com]
  • Canine fucosidosis is found in the English Springer Spaniel.Typically affecting dogs between 18 months and four years, symptoms include: Loss of learned behavior Change in temperament Blindness Loss of balance Deafness Weight loss From the onset, disease[en.wikipedia.org]
Mild Clinical Course
  • It is interesting that this patient has a relatively mild clinical course despite the absence of the mRNA. This case also indicates the difficulty in determining the phenotype from the genotype in fucosidosis.[ncbi.nlm.nih.gov]
Failure to Thrive
  • A 7-year-old female patient was admitted to our outpatient clinic with complaints of failure to thrive, loss of acquired motor skills, and generalized dystonia.[annalsofian.org]
Macroglossia
  • The infantile form (type I) features psychomotor deterioration, MUSCLE SPASTICITY, coarse facial features, growth retardation, skeletal abnormalities, visceromegaly, SEIZURES, recurrent infections, and MACROGLOSSIA, with death occurring in the first decade[connects.catalyst.harvard.edu]
  • Her tongue was protruding due to macroglossia. There were red streaks on gingivae and blue-brown spots on tongue. She had no angiokeratomas in genital area and trunk. There was no hepatosplenomegaly.[annalsofian.org]
  • The infantile form (type i) features psychomotor deterioration, muscle spasticity, coarse facial features, growth retardation, skeletal abnormalities, visceromegaly, seizures, recurrent infections, and macroglossia, with death occurring in the first decade[icd10data.com]
Dental Abscess
  • He presented with recurrent sinopulmonary infection and otitis media in addition to paronychia and a periapical dental abscess.[ncbi.nlm.nih.gov]
Cardiomegaly
  • Fucosidosis is a rare lysosomal storage disorder with the clinical features of mental retardation, cardiomegaly, dysostosis multiplex, progressive neurologic deterioration, and early death.[ncbi.nlm.nih.gov]
  • […] fucosidosis [ fu″ko-sĭ-do sis ] a hereditary disease due to deficient enzymatic activity of fucosidase and resulting in accumulation of fucose in all tissues; marked by progressive cerebral degeneration, muscle weakness with eventual spasticity, emaciation, cardiomegaly[medical-dictionary.thefreedictionary.com]
  • If types are used, the symptoms are usually classified as: Type I (also called severe) begins in the first 3-18 months of life coarse facial features enlarged liver (hepatomegaly), spleen (splenomegaly), and/or heart (cardiomegaly) abnormal bone formation[dermaamin.com]
  • […] progressive motor deterioration: initially hypotonia before spasticity manifests coarse facies dwarfism and other muscoskeletal anomalies recurrent respiratory infections angiokeratomas organomegaly : glossomegaly , hepatomegaly , splenomegaly , and cardiomegaly[radiopaedia.org]
  • […] from a defect in glyoxalate metabolism Lysosomal storage disease caused by defective alpha-l-fucosidase and accumulation of fucose containing glycoconjugates; clinical symptoms include psychomotor deterioration, growth retardation, hepatosplenomegaly, cardiomegaly[icd9data.com]
Acrocyanosis
  • Other cutaneous features in this patient included distal transverse purple nail bands, acrocyanosis and a naevus anaemicus. Histology and electron microscopy of skin papules was consistent with angiokeratoma.[ncbi.nlm.nih.gov]
Hepatomegaly
  • He had a coarse face, hepatomegaly and generalized spasticity. His initial laboratory examination revealed negative urine screening column chromatography for mucopolysaccharidosis.[ncbi.nlm.nih.gov]
  • Clinical signs include facial dysmorphism, dysostosis multiplex, moderate hepatomegaly, severe intellectual deficit, deafness, and according to age, angiokeratomas.[uniprot.org]
  • Clinical features include angiokeratoma, progressive psychomotor retardation, neurologic signs, coarse facial features, hepatomegaly, and dysostosis multiplex.[omicsonline.org]
  • If types are used, the symptoms are usually classified as: Type I (also called severe) begins in the first 3-18 months of life coarse facial features enlarged liver (hepatomegaly), spleen (splenomegaly), and/or heart (cardiomegaly) abnormal bone formation[dermaamin.com]
  • […] disability with eventual dementia progressive motor deterioration: initially hypotonia before spasticity manifests coarse facies dwarfism and other muscoskeletal anomalies recurrent respiratory infections angiokeratomas organomegaly : glossomegaly , hepatomegaly[radiopaedia.org]
Hepatosplenomegaly
  • It causes mental retardation, neurological deterioration, coarse facial features, thickened skin, and hepatosplenomegaly.[medical-dictionary.thefreedictionary.com]
  • There was no hepatosplenomegaly. Her neurological examination revealed spastic tetraparesis dominated by dystonic posturing. Increased tendon reflexes and multilevel joint contractures were observed.[annalsofian.org]
  • The more severe (infantile or type I) phenotype includes rapidly progressive mental retardation, hepatosplenomegaly, severe dysostosis multiplex, and often death between 3 and 12 years of age.[ommbid.mhmedical.com]
  • […] oxalate, resulting from a defect in glyoxalate metabolism Lysosomal storage disease caused by defective alpha-l-fucosidase and accumulation of fucose containing glycoconjugates; clinical symptoms include psychomotor deterioration, growth retardation, hepatosplenomegaly[icd9data.com]
  • 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[rarediseases.org]
Hearing Impairment
  • Other signs related to fucosidosis include visceromegaly that can affect the spleen, liver, and heart, epilepsy, hearing impairment or total hearing loss, kyphoscoliosis, and persistent respiratory infections.[symptoma.com]
Muscle Spasticity
  • The infantile form (type I) features psychomotor deterioration, MUSCLE SPASTICITY, coarse facial features, growth retardation, skeletal abnormalities, visceromegaly, SEIZURES, recurrent infections, and MACROGLOSSIA, with death occurring in the first decade[connects.catalyst.harvard.edu]
  • The infantile form (type i) features psychomotor deterioration, muscle spasticity, coarse facial features, growth retardation, skeletal abnormalities, visceromegaly, seizures, recurrent infections, and macroglossia, with death occurring in the first decade[icd10data.com]
Coxa Valga
  • The epiphyseal centers not well developed, the pelvis is poorly formed with small femoral heads and coxa valga. The clavicles are short, thick and irregular and the ribs are oar shaped. Phalanges are shortened and trapezoidal in shape.[themedicalbiochemistrypage.org]
Osteopenia
  • However, this means that the child will have to take steroid medication for the rest of his or her life, which has serious side effects such as diabetes, glaucoma, bone weakening ( osteopenia ), and high blood pressure.[rarediseases.about.com]
Coarse Face
  • He had a coarse face, hepatomegaly and generalized spasticity. His initial laboratory examination revealed negative urine screening column chromatography for mucopolysaccharidosis.[ncbi.nlm.nih.gov]
Psychomotor Retardation
  • In type 2, patients have angiokeratoma, milder psychomotor retardation and neurologic signs, longer survival, and normal salinity in the sweat.[ncbi.nlm.nih.gov]
  • Three sisters with adult fucosidosis showed prominent psychomotor retardation, gargoyle features, and angiokeratoma corporis diffusum, meeting the criteria for type II fucosidosis.[ncbi.nlm.nih.gov]
  • Because of the slowly progressing psychomotor retardation and recurrent upper respiratory tract infections that the prognosis for patients with this disease is poor. Treatment appears to be aimed at early diagnosis through amniocentesis.[ncbi.nlm.nih.gov]
Seizure
  • Fucosidosis is a rare autosomal recessive lysosomal storage disease with the main clinical findings of progressive neuromotor deterioration, seizures, coarse facial features, dysostosis multiplex, angiokeratoma corporis diffusum, visceromegaly, recurrent[ncbi.nlm.nih.gov]
  • […] by deficiency of lysosomal alpha-fucosidase and is manifested clinically by progressive mental and motor deterioration, coarse facies, growth retardation, recurrent infections, dysostosis multiplex, angiokeratoma corporis diffusum, visceromegaly and seizures[ncbi.nlm.nih.gov]
  • […] is an extremely rare lysosomal storage disorder characterized by a highly variable phenotype with common manifestations including neurologic deterioration, coarse facial features, growth retardation, and recurrent sinopulmonary infections, as well as seizures[orpha.net]
  • Its clinical phenotypes include progressive neurological and mental deterioration, coarse facial features, growth retardation, visceromegaly, angiokeratomas, and seizures.[ncbi.nlm.nih.gov]
  • Treatment will focus on the symptoms an individual has, such as seizure medication.[en.wikipedia.org]
Dystonia
  • She was bound to a wheelchair at 6 years of age, and developed dystonia at the age of 13 years.[ncbi.nlm.nih.gov]
  • Even among the 4 other reported fucosidosis families having one or more individuals homozygous for this same (Q422X) mutation there was no previous report of dystonia.[ncbi.nlm.nih.gov]
  • First child of family was investigated because of severe spasticity and generalized dystonia.[annalsofian.org]
  • ....Benjamin R.N. 2014 17 Oligodendrocyte loss during the disease course in a canine model of the lysosomal storage disease fucosidosis. ( 24806306 ) Fletcher J.L....Taylor R.M. 2014 18 Late diagnosis of fucosidosis in a child with progressive fixed dystonia[malacards.org]
  • Fucosidosis with dystonia. Neuropediatrics 1995 ; 26 : 325 -327 Ismail EAR, Rudwan M, Shafik MH. Fucosidosis: immunological studies and chronological neuroradiological changes.[ajnr.org]
Delayed Development of Motor Skills
  • People with this condition often have delayed development of motor skills such as walking; the skills they do acquire deteriorate over time.[ghr.nlm.nih.gov]
  • People with this condition often have delayed development of motor skills such as walking, and the skills they do acquire often deteriorate over time. In severe cases, symptoms appear in infancy; in milder cases, symptoms begin at age 1 or 2.[diseaseinfosearch.org]

Workup

The first step towards a successful diagnosis of Fucosidosis is a detailed medical history and a meticulous clinical examination. The patients are, in the majority of the cases, in their first year of life and parents report signs associated with mental retardation; the infant also appears to be lacking in terms of growth and neurological development. Characteristic skeletal and facial features are also noticeable and may indicate the diagnosis. Further tests that may be employed in order to diagnose Fucosidosis include:

  • Electron microscopy samples are harvested from the heart, liver, spleen, lung and other viscera. Electron microscopy reveals intracellular vacuoles, either clear or filled with granulomatous/lamellar bodies.
  • Magnetic resonance imaging (MRI), computerized tomography (CT) are both employed in order to detect degenerative alterations of the cerebral parenchyma. The use of CT scans has specifically increased during the recent years [5] [6] [7].
  • Urinalysis may illustrate fucose-containing complex compounds.
  • Enzyme assays show decreased activity of the enzyme alpha-L-fucosidase.
  • Prenatal testing: Fucosidosis can also be confirmed prenatally, by means of chorionic villus sampling (CVS) and amniocentesis.

Treatment

  • However, due to the risks and exclusion criteria of this treatment additional therapies are required.[ncbi.nlm.nih.gov]
  • Treatment The first line of treatment for Blackfan Diamond anemia is to give the child steroid medication, usually prednisone.[rarediseases.about.com]
  • Treatment: There is no treatment or way to reverse the disease. Treatment will focus on the symptoms an individual has, such as seizure medication.[en.wikipedia.org]
  • Your donation is vital to help us continue our services supporting families and funding research into treatments for the coming year.[mpssociety.co.uk]
  • Is there a treatment for Fucosidosis? Individuals with Fucosidosis should have routine follow-up with Genetics, Neurology, Ophthalmology, and other specialists as needed.[web.archive.org]

Prognosis

  • Because of the slowly progressing psychomotor retardation and recurrent upper respiratory tract infections that the prognosis for patients with this disease is poor. Treatment appears to be aimed at early diagnosis through amniocentesis.[ncbi.nlm.nih.gov]
  • Diagnosis and Prognosis: Pediatricians and neurologists usually make the diagnosis. No specific treatment is available for the primary disease but supportive treatment such as respiratory therapy can help many patients.[disorders.eyes.arizona.edu]
  • Treatment and prognosis Although bone marrow transplant has been reported as an effective treatment, this is very uncommonly performed, and only after careful patient selection 1,8 .[radiopaedia.org]

Epidemiology

  • We conclude that the epidemiology of these diseases can vary regionally, and we stress the need for similar surveys in other Latin American countries. [Indexed for MEDLINE] Free full text[ncbi.nlm.nih.gov]
Sex distribution
Age distribution

Prevention

  • Addition of placental alpha-L-fucosidase to the culture medium of fucosidosis fibroblasts prevented excessive accumulation of fucose-containing material and accelerated the breakdown of material accumulated prior to enzyme uptake.[ncbi.nlm.nih.gov]
  • Bone marrow transplantation conditioning was with a regimen of busulphan, thiotepa and cyclophosphamide; in vivo Campath 1G, cyclosporin A and short course methotrexate were given to prevent graft-versus-host disease.[ncbi.nlm.nih.gov]
  • This DNA vaccine has the potential to be a safe and effective therapy to prevent Alzheimer disease. He described Machado-Joseph disease (MJD), an autosomal dominant ataxia, with William Nyhan, M.D. Ph.D, in 1976, for the first time.[books.google.de]

References

Article

  1. Willems PJ, Gatti R, Darby JK, et al. Fucosidosis Revisited: A Review of 77 Patients. Am J Med Genet. 1991;38(1):111–131
  2. Folkerth RD. Abnormalities of developing white matter in lysosomal storage diseases. J Neuropathol Exp Neurol. 1999;58:887–902.
  3. Prietsch V, Arnold S, Kraegeloh-Mann I, et al. Severe hypomyelination as the leading neuroradiological sign in a patient with fucosidosis. Neuropediatr. 2008;39:51–4
  4. Steenweg ME, Vanderver A, Blaser S, et al. Magnetic resonance imaging pattern recognition in hypomyelinating disorders. Brain. 2010 Oct;133(10):2971-82
  5. Terespolsky D, Clark JT, Blaser SI. Evolution of the Neuroimaging Changes in Fucosidosis Type II. J Inherit Metab Dis. 1996;19(6):775–781
  6. Smith-Bindman R, Lipson J, Marcus R, et al. Radiation dose associated with common computed tomography examinations and the associated lifetime attributable risk of cancer. Arch Intern Med. 2009 Dec 14;169(22):2078-86.
  7. Berrington de González A, Mahesh M, Kim KP, et al. Projected cancer risks from computed tomographic scans performed in the United States in 2007. Arch Intern Med. 2009 Dec 14;169(22):2071-7.

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Last updated: 2019-07-11 22:29