Giant axonal neuropathy
Encyclopedia
Giant axonal neuropathy is a rare, autosomal recessive
neurological disorder that causes disorganization of neurofilament
s. Neurofilaments form a structural framework that helps to define the shape and size of neuron
s and are essential for normal nerve
function.
, causing individuals with this disorder to have problems walking. Later, normal sensation, coordination, strength, and reflexes become affected. Hearing or vision problems may also occur. Abnormally kinky hair is characteristic of giant axonal neuropathy, appearing in almost all cases. As the disorder progresses, central nervous system
becomes involved, which may cause a gradual decline in mental function, loss of control of body movement, and seizures.
Giant axonal neuropathy results from mutation
s in the GAN gene
, which codes for the protein
gigaxonin. This alters the shape of the protein, changing how it interacts with other proteins when organizing the structure of the neuron
.
Neurons affected by the altered protein accumulate excess neurofilaments in the axon
, the long extension from the nerve cell that transmits its signal to other nerve cells and to muscles. These enlarged or 'giant' axons cannot transmit signals properly, and eventually deteriorate, resulting in the range of neurological anomalies associated with the disorder.
This disease is an autosomal recessive disorder, which means the defective gene is located on an autosome
, and both parents must have one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are carriers
, but are usually not affected by the disorder.
Recessive
In genetics, the term "recessive gene" refers to an allele that causes a phenotype that is only seen in a homozygous genotype and never in a heterozygous genotype. Every person has two copies of every gene on autosomal chromosomes, one from mother and one from father...
neurological disorder that causes disorganization of neurofilament
Neurofilament
Neurofilaments are the 10 nanometer intermediate filaments found specifically in neurons. They are a major component of the cell's cytoskeleton, and provide support for normal axonal radial growth...
s. Neurofilaments form a structural framework that helps to define the shape and size of neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
s and are essential for normal 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...
function.
Diagnosis
Giant axonal neuropathy usually appears in infancy or early childhood, and is progressive. Early signs of the disorder often present in the peripheral nervous systemNervous 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...
, causing individuals with this disorder to have problems walking. Later, normal sensation, coordination, strength, and reflexes become affected. Hearing or vision problems may also occur. Abnormally kinky hair is characteristic of giant axonal neuropathy, appearing in almost all cases. As the disorder progresses, central nervous system
Central nervous system
The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...
becomes involved, which may cause a gradual decline in mental function, loss of control of body movement, and seizures.
Genetics
Mutation
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 GAN 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...
, which codes for the protein
Protein
Proteins are biochemical compounds consisting of one or more polypeptides typically folded into a globular or fibrous form, facilitating a biological function. A polypeptide is a single linear polymer chain of amino acids bonded together by peptide bonds between the carboxyl and amino groups of...
gigaxonin. This alters the shape of the protein, changing how it interacts with other proteins when organizing the structure of the neuron
Neuron
A neuron is an electrically excitable cell that processes and transmits information by electrical and chemical signaling. Chemical signaling occurs via synapses, specialized connections with other cells. Neurons connect to each other to form networks. Neurons are the core components of the nervous...
.
Neurons affected by the altered protein accumulate excess neurofilaments in the axon
Axon
An axon is a long, slender projection of a nerve cell, or neuron, that conducts electrical impulses away from the neuron's cell body or soma....
, the long extension from the nerve cell that transmits its signal to other nerve cells and to muscles. These enlarged or 'giant' axons cannot transmit signals properly, and eventually deteriorate, resulting in the range of neurological anomalies associated with the disorder.
This disease is an autosomal recessive disorder, which means the defective gene is located on an autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
, and both parents must have one copy of the defective gene in order to have a child born with the disorder. The parents of a child with an autosomal recessive disorder are carriers
Genetic carrier
A genetic carrier , is a person or other organism that has inherited a genetic trait or mutation, but who does not display that trait or show symptoms of the disease. They are, however, able to pass the gene onto their offspring, who may then express the gene...
, but are usually not affected by the disorder.