Krabbe disease
Encyclopedia
Krabbe disease is a rare, often fatal degenerative disorder that affects the myelin
sheath of the nervous system
. This condition is inherited in an autosomal recessive pattern. The disease is named for the Danish neurologist
Knud Haraldsen Krabbe.
communities in Israel
. Scandinavian countries have comparatively high rates of the disease, reported to be 1 in 50,000 births.
Krabbe disease may also be found in cats and in dogs, particularly Westies
and Cairn Terrier
s.
s in the GALC gene
located on chromosome
14
(14q31), which causes a deficiency of an enzyme
called galactocerebrosidase. The build up of unmetabolized lipids affects the growth of the nerve's protective myelin sheath (the covering that insulates many nerve
s) and causes severe degeneration of motor skills. As part of a group of disorders known as leukodystrophies
, Krabbe disease results from the imperfect growth and development of myelin.
GALC deficiency also results in a build up of a glycosphingolipid called Psychosine. It has been suggested Psychosine causes axonal degeneration in both the CNS and PNS by disrupting lipid rafts and may play a role in Krabbe disease.
s, limb stiffness, seizure
s, feeding difficulties, vomiting, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms for those of cerebral palsy
. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy, optic nerve enlargement, blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. There are also juvenile- and adult-onset cases of Krabbe disease, which have similar symptoms but slower progression.
(e.g.; luxol fast blue) may be used to aid diagnosis.
transplantation
has been shown to benefit cases early in the course of the disease. Generally, treatment for the disorder is symptomatic and supportive. Physical therapy
may help maintain or increase muscle
tone and circulation. A recent study in the New England Journal of Medicine
reports that cord blood
transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.
quarterback Jim Kelly
has been a leader in gaining recognition and research funding for Krabbe disease, following the diagnosis of his son, Hunter, in 1997. Hunter Kelly died of the disease on August 5, 2005 at the age of 8.
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
sheath of the nervous system
Nervous system
The nervous system is an organ system containing a network of specialized cells called neurons that coordinate the actions of an animal and transmit signals between different parts of its body. In most animals the nervous system consists of two parts, central and peripheral. The central nervous...
. This condition is inherited in an autosomal recessive pattern. The disease is named for the Danish neurologist
Neurologist
A neurologist is a physician who specializes in neurology, and is trained to investigate, or diagnose and treat neurological disorders.Neurology is the medical specialty related to the human nervous system. The nervous system encompasses the brain, spinal cord, and peripheral nerves. A specialist...
Knud Haraldsen Krabbe.
Incidence
Krabbe disease occurs in about 1 in 100,000 births. A higher incidence, about 1 in 6,000, has been reported in some ArabArab
Arab people, also known as Arabs , are a panethnicity primarily living in the Arab world, which is located in Western Asia and North Africa. They are identified as such on one or more of genealogical, linguistic, or cultural grounds, with tribal affiliations, and intra-tribal relationships playing...
communities in Israel
Israel
The State of Israel is a parliamentary republic located in the Middle East, along the eastern shore of the Mediterranean Sea...
. Scandinavian countries have comparatively high rates of the disease, reported to be 1 in 50,000 births.
Krabbe disease may also be found in cats and in dogs, particularly Westies
West Highland White Terrier
The West Highland White Terrier, commonly known as the Westie, is a Scottish breed of dog with a distinctive white coat. The modern breed is descended from a number of breeding programes of white terriers in Scotland prior to the 20th century...
and Cairn Terrier
Cairn Terrier
The Cairn Terrier is the oldest of the terrier breeds, originating in the Scottish Highlands and recognized as one of Scotland's earliest working dogs...
s.
Causes
Krabbe disease is caused by mutationMutation
In molecular biology and genetics, mutations are changes in a genomic sequence: the DNA sequence of a cell's genome or the DNA or RNA sequence of a virus. They can be defined as sudden and spontaneous changes in the cell. Mutations are caused by radiation, viruses, transposons and mutagenic...
s in the GALC gene
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
located on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
14
Chromosome 14 (human)
rightChromosome14 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 14 spans about 109 million base pairs and represents between 3 and 3.5% of the total DNA in cells....
(14q31), which causes a deficiency of an enzyme
Enzyme
Enzymes are proteins that catalyze chemical reactions. In enzymatic reactions, the molecules at the beginning of the process, called substrates, are converted into different molecules, called products. Almost all chemical reactions in a biological cell need enzymes in order to occur at rates...
called galactocerebrosidase. The build up of unmetabolized lipids affects the growth of the nerve's protective myelin sheath (the covering that insulates many nerve
Nerve
A peripheral nerve, or simply nerve, is an enclosed, cable-like bundle of peripheral axons . A nerve provides a common pathway for the electrochemical nerve impulses that are transmitted along each of the axons. Nerves are found only in the peripheral nervous system...
s) and causes severe degeneration of motor skills. As part of a group of disorders known as leukodystrophies
Leukodystrophy
Leukodystrophy refers to a group of disorders characterized by dysfunction of the white matter of the brain. The leukodystrophies are caused by imperfect growth or development of the myelin sheath, the fatty covering that acts as an insulator around nerve fibers...
, Krabbe disease results from the imperfect growth and development of myelin.
GALC deficiency also results in a build up of a glycosphingolipid called Psychosine. It has been suggested Psychosine causes axonal degeneration in both the CNS and PNS by disrupting lipid rafts and may play a role in Krabbe disease.
Symptoms
Infants with Krabbe disease are normal at birth. Symptoms begin between the ages of 3 and 6 months with irritability, feverFever
Fever is a common medical sign characterized by an elevation of temperature above the normal range of due to an increase in the body temperature regulatory set-point. This increase in set-point triggers increased muscle tone and shivering.As a person's temperature increases, there is, in...
s, limb stiffness, seizure
Seizure
An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...
s, feeding difficulties, vomiting, and slowing of mental and motor development. In the first stages of the disease, doctors often mistake the symptoms for those of cerebral palsy
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
. Other symptoms include muscle weakness, spasticity, deafness, optic atrophy, optic nerve enlargement, blindness, paralysis, and difficulty when swallowing. Prolonged weight loss may also occur. There are also juvenile- and adult-onset cases of Krabbe disease, which have similar symptoms but slower progression.
Diagnosis
The disease may be diagnosed by its characteristic grouping of certain cells (multinucleated globoid cells), nerve demyelination and degeneration, and destruction of brain cells. Special stains for myelinMyelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
(e.g.; luxol fast blue) may be used to aid diagnosis.
Prognosis
In infants, the disease is generally fatal before age 2. Patients with late-onset Krabbe disease tend to have a slower progression of the disease and live significantly longer.Treatment
Although there is no cure for Krabbe disease, bone marrowBone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
transplantation
Organ transplant
Organ transplantation is the moving of an organ from one body to another or from a donor site on the patient's own body, for the purpose of replacing the recipient's damaged or absent organ. The emerging field of regenerative medicine is allowing scientists and engineers to create organs to be...
has been shown to benefit cases early in the course of the disease. Generally, treatment for the disorder is symptomatic and supportive. Physical therapy
Physical therapy
Physical therapy , often abbreviated PT, is a health care profession. Physical therapy is concerned with identifying and maximizing quality of life and movement potential within the spheres of promotion, prevention, diagnosis, treatment/intervention,and rehabilitation...
may help maintain or increase muscle
Muscle
Muscle is a contractile tissue of animals and is derived from the mesodermal layer of embryonic germ cells. Muscle cells contain contractile filaments that move past each other and change the size of the cell. They are classified as skeletal, cardiac, or smooth muscles. Their function is to...
tone and circulation. A recent study in the New England Journal of Medicine
New England Journal of Medicine
The New England Journal of Medicine is an English-language peer-reviewed medical journal published by the Massachusetts Medical Society. It describes itself as the oldest continuously published medical journal in the world.-History:...
reports that cord blood
Cord blood
Umbilical cord blood is blood that remains in the placenta and in the attached umbilical cord after childbirth. Cord blood is collected because it contains stem cells which can be used to treat hematopoietic and genetic disorders.-Collection:...
transplants have been successful in stopping the disease as long as they are given before overt symptoms appear.
Advocacy
Former Buffalo BillsBuffalo Bills
The Buffalo Bills are a professional football team based in Buffalo, New York. They are currently members of the East Division of the American Football Conference in the National Football League...
quarterback Jim Kelly
Jim Kelly
James Edward Kelly is a former American football quarterback in the NFL for the Buffalo Bills and the USFL's Houston Gamblers....
has been a leader in gaining recognition and research funding for Krabbe disease, following the diagnosis of his son, Hunter, in 1997. Hunter Kelly died of the disease on August 5, 2005 at the age of 8.
External links
- Dr. Maria Escolar Speaks about Krabbe Disease - Infantile Krabbe Disease Parent Education Program
- GeneReviews/NCBI/NIH/UW entry on Krabbe disease
- OMIM entries on Krabbe disease
- The Stennis Foundation
- The Hunter's Hope Foundation
- DTI as a Tool to Identify Infants with Krabbe Disease in Need of Urgent Treatment - Study to aid detection and treatment of Krabbe Disease