Adrenoleukodystrophy, or ALD, is a deadly genetic disease that affects 1 in 18 people. It most severely affects boys and men. This brain disorder destroys myelin, the protective sheath that surrounds the brain's neurons -- the nerve cells that allow us to think and to control our muscles. It knows no racial, ethnic or geographic barriers.
Normal, healthy boys suddenly begin to regress. At first, they simply show behavioral problems, such as withdrawal or difficulty concentrating. Gradually, as the disease ravages their brain, their symptoms grow worse, including blindness and deafness, seizures, loss of muscle control, and progressive dementia.
This relentless downward spiral leads to either death or permanent disability, usually within 2 to 5 years from diagnosis. Today, new scientific knowledge offers hope for the successful treatment and prevention of ALD.
Like a venture capital firm, we identify gaps in the development process, seek out creative solutions to fill those gaps, and deliver the resources that can develop these great ideas into concrete projects, and projects into therapies that can transform the lives of children with ALD and their families.
Adrenoleukodystrophy, or ALD, is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter. Without that sheath, the neurons cannot conduct action potentials—in other words, they stop telling the muscles and other elements of the central nervous system what to do. This sequence of events appears to be related to an abnormal accumulation of saturated very-long-chain fatty acids VLCFA in the serum and tissues of the central nervous system, which sets off an abnormal immune response that leads to demyelination.
It is unclear exactly how this chain of events works, but scientists do know that it has its roots in genetics. Everyone has two sex chromosomes: women have two X chromosomes and men have an X and a Y chromosome. If a woman inherits the abnormal X chromosome, she still has a normal, second X chromosome to help balance out the affects of the mutation. Boys and men do not have a second X chromosome, so if they inherit this genetic abnormality, they will get the disease. It is characterized by an inflammatory process that destroys the myelin, causing relentless progressive deterioration to a vegetative state or death, usually within five years.
The majority of other cases of the disease occur as the adult form, known as AMN. In about half of the sons who inherit the mutated ALD gene, symptoms of the disease do not develop until young adulthood, and in general, they progress more slowly. Beginning in their 20s and 30s, these young men exhibit neurological based motor lesions in their extremities. These lesions progress over many years and are inevitably accompanied by moderate to severe handicap. In approximately one third of these patients the central nervous system also becomes involved.
These young men undergo the same mental and physical deterioration as the previously described boys. There is no effective treatment for the adult onset of ALD, which is commonly referred to as adrenomyeloneuropathy AMN ; rather, medication and therapies are employed in a palliative manner. The adrenal glands produce a variety of hormones that control levels of sugar, sodium, and potassium in the body, and help it respond to stress. Fortunately, this aspect of ALD is easily treated, simply by taking a steroid pill daily and adjusting the dose in times of stress or illness.
Although women who carry the ALD gene mutation do not generally develop the brain disease itself, some display mild symptoms of the disorder. These symptoms usually develop after age 35, and primarily include progressive stiffness, weakness, or paralysis of the lower limbs, numbness, pain in the joints, and urinary problems. Home What is ALD? What is ALD? Adrenoleukodystrophy Adrenoleukodystrophy, or ALD, is an x-linked metabolic disorder, characterized by progressive neurologic deterioration due to demyelination of the cerebral white matter.
ALD takes several forms, which can vary widely in their severity and progression. Fortunately, this aspect of ALD is easily treated, simply by taking a steroid pill daily and adjusting the dose in times of stress or illness Female ALD Although women who carry the ALD gene mutation do not generally develop the brain disease itself, some display mild symptoms of the disorder.This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person.
People with the same disease may not have all the symptoms listed. The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. If you need medical advice, you can look for doctors or other healthcare professionals who have experience with this disease. You may find these specialists through advocacy organizations, clinical trials, or articles published in medical journals.
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National Institutes of Health. COVID is an emerging, rapidly evolving situation. Menu Search Home Diseases X-linked adrenoleukodystrophy. You can help advance rare disease research! Metabolic disorders. Adrenomyeloneuropathy ; X-linked cerebral adrenoleukodystrophy.
This disease is grouped under:.
Disorder of peroxisomal alpha- beta- and omega-oxidation ; Disorders with deficiency of a single peroxisomal enzyme ; Leukodystrophy ; Disorder of peroxisomal alpha- beta- and omega-oxidation ; Disorders with deficiency of a single peroxisomal enzyme ; Leukodystrophy ; Peroxisomal beta-oxidation disorder ; Peroxisome disorders See More. Summary Summary. Symptoms Symptoms.Adrenoleukodystrophy uh-dree-noh-loo-koh-DIS-truh-fee is a type of hereditary genetic condition that damages the membrane myelin sheath that insulates nerve cells in your brain.
X-linked ALD affects males more severely than females, who carry the disease. Adrenoleukodystrophy care at Mayo Clinic. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version.
What is ALD?
Overview Adrenoleukodystrophy uh-dree-noh-loo-koh-DIS-truh-fee is a type of hereditary genetic condition that damages the membrane myelin sheath that insulates nerve cells in your brain.
Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Adrenoleukodystrophy information page. National Institute of Neurological Disorders and Stroke. Accessed Sept. National Library of Medicine. X-linked adrenoleukodystrophy. Genetics Home Reference. Kliegman RM, et al. Adrenocortical insufficiency. In: Nelson Textbook of Pediatrics. Philadelphia, Pa. Tran C, et al. Long-term outcome of patients with X-linked adrenoleukodystrophy: A retrospective cohort study.
European Journal of Paediatric Neurology. Wanders RJ, et al. Riggin EA. Allscripts EPSi. Mayo Clinic, Rochester, Minn. July 20, Eichler F, et al. Hematopoietic stem-cell gene therapy for cerebral adrenoleukodystrophy. The New England Journal of Medicine. In press. Accessed Oct. Mayo Clinic Marketplace Check out these best-sellers and special offers on books and newsletters from Mayo Clinic.There are a wide range of clinical severities of X-linked adrenoleukodystrophy X-ALDand these have been classified into six broad categories: childhood cerebral ALD, adolescent cerebral ALD, adult cerebral, adrenomyeloneuropathy, adrenal insufficiency-only, and symptomatic heterozygotes.
The clinical phenotypes of each are described below. Onset of childhood cerebral ALD occurs between the ages of 2 and Up to the point of onset, development is normal. The most common initial symptoms are difficulty in school, behavioral disturbance, impaired vision, or impaired hearing. After initial neurological symptoms appear, the health of the patients deteriorates rapidly.
Further symptoms may include dementia, poor coordination, seizures, hyperactivity, difficulty with speech, and headaches. The average time between the initial symptoms and a vegetative state where the patient is bedridden or death is approximately 2 years, although it can range anywhere from 6 months to 20 years. The symptoms are similar to those of childhood cerebral ALD, though progression of the disease may be somewhat slower.
The first symptoms of AMN usually occur in the twenties. Adrenal impairment occurs, and other major manifestations may include difficulty with walking, urinary disturbance and impotence, cognitive defects, emotional disturbances, and depression.
The disease progresses slowly, and within 5 to 15 years the patient will generally need the aid of a cane or wheelchair. Age of onset varies from the twenties to the fifties. The symptoms are similar to those of schizophrenia with dementia, and the progression of the disorder is rapid. The average time from the initial symptoms to vegetative state or death is approximately years.
The symptoms can range from very mild to very severe. They resemble those of other ALD patients, with the exception that heterozygote women rarely have impaired adrenal function. X-ALD is diagnosed by a simple blood test that analyzes the amount of very long chain fatty acids; the levels of these molecules are elevated in X-ALD.
A DNA-based blood test is available. This test permits accurate identification of carriers by genetic testing, and if it is normal can assure a woman that she is not a carrier.
Diagnostic testing, carrier screening and prenatal diagnosis are available and testing protocols are available from the United Leukodystrophy Foundation ULF. Additionally, the patient will be evaluated for adrenal insufficiency by another blood testas this is a common symptom of the disease that can be corrected. The peroxisome is a cellular compartment that is responsible for the breakdown of certain types of fatty acids very long chain fatty acids. In X-ALD, this ability is impaired, resulting in the accumulation of very long chain fatty acids.
This leads to the breakdown of the myelin sheath, resulting in the neurologic problems characteristic of leukodystrophies. This protein resides in the wall of the peroxisome, and is involved in the breakdown of fatty acids. However, its exact role in this process is currently unclear. It is worth noting that the specific mutation present in the ALD gene does not necessarily predict the course of the disease.
Practically, this means that the fact that two members of a single family harbor the same mutation does NOT mean that the clinical course of the disease will be identical.
There are two human sex chromosomes — the X and the Y, and the combination of these chromsomes determines the sex of an individual.This deficiency leads to the accumulation of very-long chain fatty acids VLCFAs in plasma and tissue—primarily of the nervous system and adrenal glands. Because this disorder results from mutations in a gene on the X chromosome, males are more susceptible—it affects approximately 1 in 21, males. ALD can also develop into cerebral ALD, a severe, progressive, and life-threatening neurodegenerative form of the disease.
In most patients, cerebral ALD is a rapidly progressing disease that causes progressive behavioral, cognitive, and neurologic deficits and total disability followed by death within 5 years after onset of symptoms. References: 1.
Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Adrenoleukodystrophy — neuroendocrine pathogenesis and redefinition of natural history. Nat Rev Endocrinol. Nat Clin Pract Neurol. J Clin Endocrinol Metab.
Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening. J Pediatr. Curr Neurol Neurosci Rep. Orphanet J Rare Dis. This link will take you to a website that is outside the control of bluebird bio, Inc.
ALD primarily affects males 1 Because this disorder results from mutations in a gene on the X chromosome, males are more susceptible—it affects approximately 1 in 21, males. Even among members of the same family, it is currently not possible to predict the future phenotype of a boy with ALD without monitoring. Cancel Continue. This site is intended for use by US health care professionals only. Cookies on this website.To diagnose ALDyour doctor will review your symptoms and your medical and family history.
Your doctor will conduct a physical examination and order several tests, including:. Blood testing. These tests check for high levels of very long-chain fatty acids VLCFAs in your blood, which are a key indicator of adrenoleukodystrophy.
Doctors use blood samples for genetic testing to identify defects or mutations that cause ALD. Doctors also use blood tests to evaluate how well your adrenal glands work. Our caring team of Mayo Clinic experts can help you with your adrenoleukodystrophy -related health concerns Start Here. Adrenoleukodystrophy has no cure.
However, stem cell transplantation may stop the progression of ALD if done when neurological symptoms first appear. Doctors will focus on relieving your symptoms and slowing disease progression. In a recent clinical trial, boys with early-stage cerebral ALD were treated with gene therapy as an alternative to stem cell transplantation.
Early results from gene therapy are promising. Disease progression stabilized in 88 percent of boys who participated in the trial.
Additional research is necessary to assess long-term results and safety of gene therapy for cerebral ALD. Adrenoleukodystrophy care at Mayo Clinic. Mayo Clinic does not endorse companies or products. Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version. Diagnosis To diagnose ALDyour doctor will review your symptoms and your medical and family history.
Your doctor will conduct a physical examination and order several tests, including: Blood testing. Care at Mayo Clinic Our caring team of Mayo Clinic experts can help you with your adrenoleukodystrophy -related health concerns Start Here. Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Adrenoleukodystrophy information page. National Institute of Neurological Disorders and Stroke. Accessed Sept. National Library of Medicine.
X-linked adrenoleukodystrophy. Genetics Home Reference. Kliegman RM, et al. Adrenocortical insufficiency. In: Nelson Textbook of Pediatrics. Philadelphia, Pa.Adrenoleukodystrophy ALD is a disease linked to the X chromosome. It is a result of fatty acid buildup caused by a defect in the very long chain fatty acids transporter in peroxisomes, which then causes damage to the myelin sheath of the nervesresulting in seizures and hyperactivity.
Other symptoms include problems with speaking, listening, and understanding verbal instructions. In more detail, it is a disorder of peroxisomal fatty acid beta oxidation which results in the accumulation of very long chain fatty acids in tissues throughout the body. The most severely affected tissues are the myelin in the central nervous systemthe adrenal cortexand the Leydig cells in the testes. Clinically, ALD is a heterogeneous disorder, presenting with several distinct phenotypesand no clear pattern of genotype -phenotype correlation.
Approximately two-thirds of ALD patients will present with the childhood cerebral form of the disease, which is the most severe form. It is characterized by normal development in early childhood, followed by rapid degeneration to a vegetative state. The other forms of ALD vary in terms of onset and clinical severity, ranging from adrenal insufficiency to progressive paraparesis in early adulthood this form of the disease is typically known as adrenomyeloneuropathy.
The exact mechanism of the pathogenesis of the various forms of ALD is not known. Biochemically, individuals with ALD show very high levels of unbranched, saturated, very long chain fatty acids, particularly cerotic acid The level of cerotic acid in plasma does not correlate with clinical presentation.
Treatment options for ALD are limited. Dietary treatment is with Lorenzo's oil. For the childhood cerebral form, stem cell transplant and gene therapy are options if the disease is detected early in the clinical course. Adrenal insufficiency in ALD patients can be successfully treated. ALD is the most common peroxisomal inborn error of metabolism, with an incidence estimated betweenandIt does not have a significantly higher incidence in any specific ethnic groups.
ALD can present in different ways. The different presentations are complicated by the pattern of X-linked recessive inheritance.
There have been seven phenotypes described in males with ABCD1 mutations and five in females. Older patients affected with the cerebral form will present with similar symptoms. Untreated, cerebral ALD is characterized by progressive demyelination leading to a vegetative state and death.
The gene ABCD1 encodes a peroxisomal membrane transporter which is responsible for transporting very long chain fatty acid substrate into the peroxisomes for degradation. Female carriers will typically avoid the most severe manifestations of the disease, but often become symptomatic later in life.