Adrenoleukodystrophy - Facts and Information
- Publish Date: 2010/03/28 - (Rev. 2014/11/28)
- Author: Thomas C. Weiss
- Contact : Disabled World
Outline: Adrenoleukodystrophy (ALD) or Schilder-Addision Disease involves closely-related inherited disorders that disrupt breakdown of fats in the body.
Defining Adrenoleukodystrophy (ALD)
Adrenoleukodystrophy (ALD) was first described in the early 1900's and referred to as, 'Schilder-Addision Disease.' ALD involves a number of closely-related inherited disorders that disrupt the breakdown of certain fats in a person's body. 'Adreno,' refers to the adrenal glands, while, 'leuko,' is the Greek word for white. 'Dystrophy,' means, 'impaired growth. Adrenoleukodystrophy (ALD) affects a person's adrenal glands and the growth of myelin.
Leukodystrophies cause damage to the myelin sheath of a person's nerve cells. Around one in every one-hundred thousand people is affected by ALD. There are three basic forms of ALD; neonatal, childhood, and adult-onset ALD. Childhood ALD is considered to be the classic form; it is also the most severe form of the disorder. Childhood ALD is progressive, commonly leading to complete disability or the death of the person affected. The disorder affects only males because the genetic defect is carried through the X-chromosome. Onset of the disorder commonly occurs between the ages of four and ten and may involve a number of symptoms that may not appear in conjunction with one another. The more common symptoms associated with ALD include poor memory and behavioral issues. Additional symptoms can include seizure activity, loss of vision, difficulties with swallowing, speech difficulties, gait and coordination problems, deafness, increased skin pigmentation, and progressive dementia.
Adult-onset ALD is also referred to as, 'adrenomyeloneuropathy,' and is milder, progresses at a slower rate, and is commonly associated with an average life span. The adult-onset form of ALD usually appears in people between the ages of twenty-one and thirty-five. The symptoms of adult-onset ALD can include weakness, stiffness, paralysis in the person's lower limbs, as well as loss of coordination. The person may experience deterioration of brain function as well. Women who carry the disorder may occasionally experience these same symptoms as well as other symptoms. The additional symptoms can include hypertonia or excessive muscle tone, ataxia, urinary problems, or mild peripheral neuropathy. The neonatal form of ALD affects both female and male infants and can cause intellectual disability, seizures, facial abnormalities, poor muscle tone, retinal degeneration, adrenal dysfunction, and enlargement of the infant's liver. The neonatal form of ALD usually progresses at a rapid rate. ALD affects every ethnic group.
Causes and Symptoms of Adrenoleukodystrophy
ALD is passed from parents to their children as an X-linked genetic trait, affecting mostly male children, although some females who carry the disorder experience milder forms of it. ALD causes problems in the person's peroxisomes, which are tiny cellular structures involved in the breakdown of large molecules of fats into smaller ones that their body can use. Persons with ALD have peroxisomes that are unable to break down a type of fat called, 'Very Long Chain Fatty Acid,' or VLCFA. Because of this, VLCFA's accumulate throughout the person's body, particularly in their adrenal glands and in their brain. Accumulation of VLCFA's interferes with their adrenal gland's ability to convert cholesterol into steroids, prompting deterioration of the myelin covering their nerve cells within the white matter of their brain and interfering with their nerve function. Fats that are usually produced through the breakdown of products of VLCFA's also cannot be produced, and due to this the person's nerve functioning is further compromised.
The adrenal glands of nearly everyone affected by ALD do not secrete sufficient amounts of hormones, something referred to as, 'adrenal insufficiency.' The symptoms the person can experience because of this may include weakness, sluggishness, hypoglycemia, weight loss, vomiting, nausea, mental changes, and darkening of their skin. Due to adrenal insufficiency, persons with ALD can experience difficulties with regulation of potassium and sodium in their bodies and may experience shock or coma, conditions that can be life-threatening. These aspects of ALD are readily treatable, making identification of persons with ALD highly important in order to prevent these complications.
The adrenal glands of almost all individuals affected with ALD do not secret a sufficient amount of hormones; this is called adrenal insufficiency. Symptoms include sluggishness, weakness, weight loss, hypoglycemia, nausea, vomiting, darkening of the skin color, and mental changes. Because adrenal insufficiency can cause problems with regulating the balance of sodium and potassium in the body, a person can go into shock and coma, which can be potentially life threatening. As this aspect of ALD is readily treatable, identifying these patients helps prevent these complications.
The symptoms of the Childhood form of ALD may include:
- Hearing loss
- Crossed eyes
- Muscle spasms
- Difficulty at school
- Swallowing difficulties
- Changes in muscle tone
- Deterioration of handwriting
- Decreased fine motor control
- Visual impairment or blindness
- Difficulty understanding spoken material
- Worsening nervous system deterioration
- Decreased understanding of verbal communication
The Adult-Onset form of ALD or, 'Adrenomyelopathy,' may include:
- Difficulty controlling urination
- Problems with thinking speed and visual memory
- Possible worsening muscle weakness or leg stiffness
The symptoms of adrenal gland failure may include:
- Muscle mass
- Loss of weight
- Muscle weakness
- Increased skin color
- Decreased appetite
Chromosome studies that look for changes or mutations in the person's ABCD1 gene, as well as blood level tests and MRI imaging of the person's head can be used to assist in achieving a diagnosis of ALD. If a doctor suspects a person has ALD, the results of an MRI imaging scan may demonstrate abnormal results, with changes that are detectable in the person's white matter. MRI images by themselves do not present a definitive diagnosis of ALD. A more definitive diagnosis of ALD can be reached through measurement of the level of VLCFA in the person's blood. In almost every male with ALD, the level of VLCFA is very high. Tests can also be performed to measure the person's adrenal function; ninety-percent of boys with the symptoms of ALD, and seventy-percent of adult males with the disorder, have adrenal glands that have been affected.
Nearly eighty-five percent of females who carry ALD present with higher than usual levels of VLCFA in their blood. Genetic testing to look for a particular mutation in the ALD gene may be performed in order to exclude any false-negatives on the part of blood testing. Women who want to be sure about their carrier status should pursue genetic testing to look for a specific mutation in the ALD gene. Before a woman can have testing to determine their carrier status; however, a mutation in the ALD gene must have already been identified in an affected member of the family.
There is no specific form of treatment for X-linked adrenoleukodystrophy (ALD), although eating a diet that is low in very long chain fatty acids, as well as consuming special oils, may lower blood levels of VLCFA's. Adrenal dysfunction is something that can be treated with steroids such as cortisol. The special oils that are suggested are referred to as, 'Lorenzo's oil,' after the son of the family that discovered the treatment. The treatment is being studied in relation to X-linked ALD, although it does not cure the disorder and might not help all of those affected. Bone marrow transplant is another form of treatment that is being pursued.
Health care professionals can provide supports that are not curative for people with different forms of ALD, helping them to manage the adrenal complications. Urologists can assist in the management of bladder complications. Physical therapists, speech therapists, and occupational therapists can help, as can behavioral psychologists and learning specialists.
Bone marrow transplantation is a promising treatment for ALD, but it is also a potentially dangerous one that carries a ten-to-twenty percent rate of death. A very small number of people who have had a bone marrow transplant had their condition stabilize; a few have even made slight improvements. All of them had the transplant at an early age. Bone marrow transplantation has drawbacks such as limited numbers of donors who are a suitable match and a significant risk that complications with develop from the transplant.