What Are The Types Of Leukodystrophy?

Leukodystrophy is an umbrella term that encompasses a group of rare genetic, metabolic, progressive diseases that cause problems with an individual's brain, peripheral nerves, and spinal cord. Leukodystrophy occurs because the myelin sheath or white matter in the brain has developed abnormally or been destroyed due to a particular gene mutation. White matter and myelin sheath are terms used to describe the substance that provides a protective and conductive covering for the nerve cells.

Similar to the way electrical wiring malfunctions without the protective plastic or rubber covering, the nerves in an individual's brain and central nervous system also malfunction without enough myelin sheath or white matter. Different components make up the myelin sheath that surrounds an individual's nerves. Each variation of leukodystrophy has adverse effects on one or more of these components, effectively producing the range of symptoms and adverse neurological effects.

Krabbe Disease

Krabbe disease is an uncommon and usually fatal disorder that falls into the classification of leukodystrophy and primarily affects the nervous system. Individuals affected by Krabbe disease do not make enough galactosylceramidase, the substance required to produce the myelin sheath that protects the nerves. Krabbe disease primarily affects infants, and most infants with it will not live past two years old. Early-onset Krabbe disease produces symptoms such as fevers, vomiting, feeding problems, excessive crying, seizures, poor coordination, muscle spasms, loss of head control, muscle tone changes, deafness, and blindness.

Late-onset Krabbe disease produces symptoms such as blindness, problems walking, poor hand coordination, rigid muscles, and muscle weakness. Diagnosis of Krabbe disease is made using blood tests, tissue biopsies, MRI scans, nerve conduction studies, eye examination, and genetic testing. Treatment consists of medications to ease symptoms, bone marrow transplant, and cord blood transplant.

X-Linked Adrenoleukodystrophy

X-linked adrenoleukodystrophy (X-ALD) is an inherited type of leukodystrophy where an individual loses the myelin sheath on the nerves in their spinal cord and brain, which has adverse effects on the adrenal glands. Patients are also known to exhibit the deficiency of adrenal hormones as a result of the degeneration of their adrenal glands. Three different forms of X-ALD exist: adrenomyeloneuropathy, adrenal-insufficiency-only, and the childhood cerebral form. All three forms of X-ALD are caused by an inherited x-linked mutation in the ABCD1 gene.

There are a range of symptoms different forms of X-ALD can produce, but collectively, the most common symptoms include seizure, learning disabilities, deafness, fatigue, weakness, urinary problems, leg stiffness, decreased appetite, increased skin pigment, vomiting, headaches, paralysis on one side of the body, and problems speaking. A blood test on long-chain fatty acids, genetic testing, and an MRI can help a physician make a diagnosis of X-ALD.

Alexander Disease

Alexander disease is a rare type of leukodystrophy best characterized by abnormal deposits of protein in the body and progressive destruction of the myelin sheath on nerve cells. Nine out of ten Alexander disease cases are caused by mutations in the GFAP gene, which helps the body produce glial fibrillary acidic protein. The mechanism that links the absence of this protein to the disease is not clear. Common symptoms of the neonatal and infantile forms of Alexander disease include seizures, motor disability, intellectual disability, physical and developmental delays, and an abnormal increase in the size of the head.

Common symptoms seen in the juvenile and adult form of Alexander disease include vomiting, speaking difficulty, moss of motor control, problems swallowing, and poor coordination. Physical examination and genetic blood testing are used to help a physician make a diagnosis of Alexander disease. Treatment for Alexander disease focuses on the mediation of symptoms because there is no cure. Medications, supplemental nutrition, physical therapy, and surgery to relieve hydrocephalus may be used as treatment.

Metachromatic Leukodystrophy

Metachromatic leukodystrophy is a disease where an individual's body does not produce enough of an enzyme referred to as arylsulfatase A. Arysulfatase A metabolizes certain fats called sulfatides, which are effectively broken down in healthy individuals. However, these sulfatides start to build up in the cells of vital organs, including the brain, spinal cord, and kidneys, when an individual lacks arylsulfatase A. Most cases of metachromatic leukodystrophy are caused by an inherited genetic mutation that causes this enzyme deficiency.

Symptoms of metachromatic leukodystrophy include abnormal muscle movement, decreased mental function, difficulty walking, frequent falls, irritability, problems with nerve function, difficulty speaking, behavior problems, decreased muscle tone, difficulty eating, incontinence, loss of muscle control, seizure, and difficulty swallowing. Blood tests, physical examination, urine tests, nerve conduction study, and MRIs are used to diagnose metachromatic leukodystrophy. Treatment for metachromatic leukodystrophy includes medications, therapy, nutritional assistance, bone marrow transplant, and cord blood transplant.

Canavan Disease

Canavan disease is an inherited form of leukodystrophy where the individual's white matter in the brain does not develop and mature completely. The white matter in the brain is responsible for creating a fatty substance referred to as myelin that creates a protective barrier and nutritional support for the axons of nerve cells. A mutation in the gene that makes aspartoacylase is what causes Canavan disease. Aspartoacylase is required to break down a substance called N-acetyl aspartate acid into the elements needed to produce myelin.

An affected individual experiences their first symptoms between three and six months old, and these include an abnormally large head, lack of motor development, abnormal muscle tone, feeding difficulties, hearing loss, paralysis, and hearing loss. Diagnosis of Canavan disease is made with the use of biochemical and genetic tests performed on an individual's blood. Urine tests may also be helpful in the diagnosis of Canavan disease. There is no cure for Canavan disease, and treatment is individualized based on a patient's symptoms and complications.