Rescuing canavan disease by redirecting metabolic processing. Canavan disease cd, a rare recessive autosomal genetic disorder, is characterized by early onset and a progressive spongy degeneration of the brain invol. Mar 27, 2019 canavan disease is a genelinked neurological disorder in which the brain degenerates into spongy tissue riddled with microscopic fluidfilled spaces. Its one of a group of over 50 rare genetic disorders that affect the central nervous system by disrupting the growth or maintenance of the myelin sheath in the brain. Canavan disease nord national organization for rare disorders. Canavan disease is an autosomal recessive disease caused by mutations in the aspa gene. Canavan is a progressive neurological genetic disorder caused by the absence of a vital enzyme known as aspartoacylase aspa. Canavan disease is a progressive leukodystrophy which means it tends to get worse through the life of the patient.
Canavan disease is particularly common in the ashkenazi jewish community 1. Canavan disease, also known as spongy degeneration of the brain, is an autosomal recessive neurodegenerative disease caused by mutations of the gene encoding the enzyme aspartoacylase matalon et al. However, it was not until 1997 that the miami childrens hospital made a patent of the gene causing this condition and began to claim royalties on testing the gene. Canavan disease information page national institute of. Canavan disease is an inherited, rare, neurological condition distinguished by degeneration which is spongy in the brain white matter is substituted by fluid filled microscopic spaces. Oct 08, 2011 picture 1 canavan disease source wikimedia canavan disease history. Canavan disease is a rare inherited disorder that damages the ability of nerve cells neurons in the brain to send and receive messages. The clinical chronic obstructive pulmonary disease copd questionnaire ccq is an easy to complete, health. Canavan research illinois cri is a nonprofit corporation and 501c3 public charity based in illinois. We collected clinical information from the parents of 60 children. Canavan disease is an autosomal recessive degenerative disorder that causes progressive damage to nerve cells in the brain, and is one of the most common degenerative cerebral diseases of infancy. Article pdf available in iranian journal of child neurology 84. Clinical copd questionnaire in patients with chronic.
Accumulation of naa results in spongiform degeneration of white matter and severe impairment of psychomotor development. It is believed to be the results of an insufficiency of the enzyme known as aspartoacylase. Mrs reveals a grossly raised naa peak, this has been described only in cases of canavan s disease and is fairly. Leukodystrophies disrupt the growth or maintenance of the myelin sheath, which is the covering that protects nerves and promotes the efficient transmission of nerve impulses. Canavan disease is an autosomal recessively inherited leukodystrophy characterized by white matter degeneration. Aspa breaks nacetylaspartate acid naa into acetate. Note extensive t2 white matter hyperintensity involving the subarcuate u fibers, posterior fossa, internal capsule and cerebellar white matter.
A natural history study of canavan disease full text view. Listing a study does not mean it has been evaluated by the u. It is caused by a deficiency of the enzyme aminoacylase 2, 2 and is one of a group of genetic diseases referred to as leukodystrophies. Canavan disease is a rare neurometabolic disease of the white matter that is associated with toxic accumulation of nacetylaspartate naa. Canavan disease is the most common degenerative neurologic disorder in infancy without racial predilection although the disease is more commonly found in children of ashkenazi jews. Leone and her core team began further research on canavan disease and gene therapy over a decade ago. Canavan disease, also known as spongiform degeneration of white matter not to be confused with creutzfeldtjakob disease or aspartoacylase deficiency, is a leukodystrophy clinically characterized by megalencephaly, severe mental and neurological deficits, and blindness. Sep, 2018 most individuals with canavan disease have the neonatalinfantile form. Canavan, an autosomalrecessive neurodegenerative disease, is caused by a deficiency of aspartoacylase. Each type of leukodystrophy is caused by an abnormality affecting a. Signs appearing in children between 3 and 6 months of age include developmental delay, significant motor slowness, enlargement of the head macrocephaly, loss of muscle tone hypotonia, poor head control, and severe feeding problems.
Canavan disease cd, a rare recessive autosomal genetic disorder, is characterized by early onset and a progressive spongy degeneration of the brain involving loss of the axons myelin sheath. The ct and mr findings in canavan disease are nonspecific and somewhat nonuni form. Leone has been responsible for the development and characterization of viral aav, adenovirus, retrovirus and nonviral vectors for the treatment of canavan disease and other disorders. Canavan research illinois also known as canavan disease research is a nonprofit corporation and 501c3 public charity based in illinois, established in april 2000 to meet a critical need to support medical research to treat, cure, and improve the quality of lives of all children battling canavan disease, a rare fatal genetic neurological disorder. An individual who inherits two mutations in the aspa gene, one from each parent, is expected to be affected with canavan disease. Pdf canavans disease is a lethal illness caused by a single gene mutation that is inherited as. A progressive, inherited disorder of the central nervous system that is caused by a deficiency of the enzyme aspartoacylase. Leukodystrophies disrupt the growth or maintenance of the myelin sheath, which is the covering that protects nerves and promotes. Life expectancy in children with canavan disease is usually until 4 years of age although there are some children who survived until teen years to 20 years of age.
Canavan disease belongs to a group of disorders known as the leukodystrophies. Pdf metabolic disorder is caused by a gene defect, environmental factors or an unknown aetiology. For example, one type of leukodystrophy, canavan disease, causes decreased muscle tone, especially in the neck, and abnormally straight legs and flexed arms. Enable javascript to view the expandcollapse boxes. Although such infants appear normal early in life, by age three to five months, hypotonia, head lag, macrocephaly, and developmental delays become apparent. The leukodystrophies are a group of rare, progressive, metabolic, genetic disorders that can affect the brain, spinal cord and often the nerves outside the central nervous system peripheral nerves. Aug 01, 2016 a natural history study of canavan disease the safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Their study spearheaded the first application of viral gene therapy to patients affected by canavan disease and reported longterm safety and clinical improvements in patients treated with gene therapy leone et al. Pdf the clinical features and diagnosis of canavans disease. Canavan disease genetic and rare diseases information. Canavan disease, the spongy degeneration of the white matter, is an autosomal recessive disorder that commonly begins in the first days and weeks of life. The carrier rates for these diseases are many times lower among the general population. Canavan disease is a genelinked neurological disorder in which the brain degenerates into spongy tissue riddled with microscopic fluidfilled spaces. At yale and thomas jefferson universities, she was the indfda sponsor of two separate gene therapy for canavan disease studies.
Canavan disease, one of the most common cerebral degenerative diseases of infancy, is a genelinked, neurological birth disorder in which the white matter of the brain degenerates into spongy tissue riddled with microscopic fluidfilled spaces. The clinical course of canavan disease pediatric neurology. Apr 14, 2020 canavan disease is a progressive, fatal, genetic disorder affecting the central nervous system, muscles, and eyes. The condition was first reported by myrtelle canavan in 1931. The enzymatic deficiency leads to the accumulation of nacetylaspartic acid naa in brain and increased concentration of nacetylaspartic. Canavan disease pictures, symptoms, treatment, causes. Initially, canavans described was described by canavan in 1931 and is now known as canavans disease. The striking features of canavans disease is a failure to attain neuro developmental milestones, abnormally decreased muscular tone, increased head circumference, seizure, atrophy of the optic nerve, and early death 1 6. Canavan disease definition is a rare, usually fatal, demyelinating disease of infancy that is characterized by spongy degeneration of the brain caused by an enzyme deficiency and that typically affects individuals of eastern european jewish ancestry. Characterization of genetic defects involving myelin continues with the identification of the gene for canavan s disease, a condition that results in the destruction of the brains white matter. Canavan disease is a hereditary condition that prevents the brains nerve cells neurons from properly sending and receiving information.
Canavan disease definition canavan disease, which results when the body produces less than normal amounts of a protein called aspartoacylase, is a fatal inherited disorder characterized by progressive damage to the brain and nervous system. You could still have a variant not covered by this test. This case demonstrates the typical clinical and imaging profile of canavan s disease. The clinical features and diagnosis of canavans disease. The responsiveness of the ccq in chronic respiratory disease patients other than copd has not been previously described. We were established in april 2000 to meet a critical need to support medical research to treat, cure, and improve the quality of lives of all children battling canavan disease, a rare fatal genetic neurological disorder. The mission of canavan disease research is to direct funding towards research aimed at developing therapies to treat and cure canavan disease while netwoking families to form an educated community poised to reach the clinic. Most children are reported to have the infantile form, becoming symptomatic between 3 and 6 months of age, after an unremarkable prenatal and perinatal course. Canavan disease nord national organization for rare. This disease is one of a group of genetic disorders called leukodystrophies. Canavan disease definition of canavan disease by merriam.
With age, children with neonatalinfantileonset canavan disease often become irritable and experience sleep disturbance, seizures, and feeding difficulties. Krabbe disease kd is a classic enzymedeficient leukodystrophy omim. Canavan disease canavan disease is a rare genetic disorder characterized by a loss of nerve cell function in the brain that worsens over time. G27r mutation, which confirmed the diagnosis of canavan disease. Dec 19, 2012 canavan disease is a hereditary leukodystrophy caused by mutations in the aspartoacylase gene aspa, leading to loss of enzyme activity and increased concentrations of the substrate n acetylaspartate naa in the brain.
Early symptoms in infancy may include increased head size, weakness, low muscle tone and loss of head control. Pdf metabolic disorder is caused by a gene defect, environmental. Canavan disease is a progressive, fatal, genetic disorder affecting the central. A person must have two variants in the aspa gene in order to have this condition. Congenital and juvenile onset forms, although uncommon, do occur. Although this fatal neurological condition can affect. Canavan disease, an autosomal recessive inherited leukodystrophy caused by an aspartoacylase deficiency, is common among children of ashkenazi jewish descent. Gale encyclopedia of neurological disorders dictionary. Canavan disease is one of a group of genetic disorders known as leukodystrophies. Canavan disease cd is a globally occurring but rare human spongiform. We report on a nonjewish female infant who presented at age 6 months with progressive macrocephaly and developmental delay. If your child has been diagnosed with canavan disease and you are wondering how the condition qualifies for disability benefits, the following information will help you understand the disability claim process and how the compassionate allowances program may help you with a fast approval of your social security disability claim. The diagnosis of neonatalinfantile canavan disease relies on demonstration of very high concentration of nacetylaspartic acid naa in the urine.
Longterm followup after gene therapy for canavan disease. Targeted aspartoacylase gene therapy reverts canavan disease. Canavan disease research cdr is an international division of. Recent research has indicated that the cells in the brain responsible for making myelin. Canavan disease has been classified as one of a group of genetic disorders known as the leukodystrophies. A sequence analysis of the aspartoacylase gene revealed compound heterozygosity for a known mutation and for the.
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