Adrenomyelopathy
Adrenomyelopathy, a form of adrenoleukodystrophy (ALD), is an inherited disorder that disrupts the metabolism of very-long-chain fatty acids (VLCFA). Primarily affecting males in their twenties or later, this condition can also present milder symptoms in female carriers due to X-linked inheritance patterns. Individuals with adrenomyelopathy may experience symptoms such as adrenal dysfunction, muscle weakness, urinary control issues, and cognitive difficulties. Diagnosis typically involves laboratory blood tests showing elevated VLCFA levels, MRI scans revealing white matter damage, and genetic testing for mutations in the ABCD1 gene. While there is no specific cure, treatments may include steroid therapy for adrenal dysfunction, dietary adjustments, and potential bone marrow or stem cell transplants. Genetic counseling is advised for families with a history of the disorder, and prenatal testing options are available. Outcomes for adrenomyelopathy are generally milder compared to the childhood cerebral form of ALD, which can lead to severe neurological decline.
Adrenomyelopathy
ALSO KNOWN AS: Adrenoleukodystrophy; adrenomyeloneuropathy; Addison disease; childhood cerebral adrenoleukodystrophy; ALD; Schilder-Addison complex
DEFINITION: Adrenomyelopathy is a category and adult form of the disease known as "adrenoleukodystrophy," or ALD. Adrenoleukodystrophy describes adrenomyelopathy and several other closely related inherited disorders that interrupt the metabolism of very-long-chain fatty acids (VLCFA).
Risk Factors
A family history of adrenoleukodystrophy that is expressed as adrenomyelopathy or related inherited disorders is the primary risk factor for the disease.
Etiology and Genetics
The accumulation of long-chain fatty acids in the nervous system, adrenal gland, and testes results in the disruption of normal activity. The condition is genetically passed down from parents to their children as an X-linked genetic trait. Although mostly males in their twenties or later are affected by adrenomyelopathy, some female carriers of the gene can have milder forms of the disease. According to the Cleveland Clinic, approximately 1 in 15,000 people worldwide are afflicted with adrenoleukodystrophy (ALD), which includes two other major categories of disease. The childhood cerebral form is characterized by a more severe onset of neurological symptoms appearing between four and ten years of age. The other common category is called "impaired adrenal gland function," also referred to as "Addison disease" or "Addison-like phenotype," in which the adrenal gland does not produce enough steroid hormones.
Genetically speaking, the ABCD1 gene that can cause ALD is located on the Xq28 region of the X chromosome, contains ten exons, and spans twenty-one kilobase pairs (kb) of genomic DNA. The gene codes for the ALD protein have been localized to the peroxisomal membrane. The gene is subject to X inactivation, placing implications for female (XX) members of a family with an X-linked inherited disorder. This X inactivation process, in which one of the two X chromosomes becomes condensed and inactive, randomly and permanently occurs at the embryonic stage. If the defective allele is on the chromosome that has been inactivated, then there will be no phenotypic manifestation of the disease. However, if the defective allele is on the active X chromosome, the other having been inactivated, then there will be a clinical expression of the disorder. In one study, mutation analysis of the ABCD1 gene in thirty-five unrelated individuals with adrenoleukodystrophy revealed that all had Xq28 ABCD1 gene mutations, 6 percent had large deletions, and 17 percent had an AG deletion in axon 5. The remainder had “private” mutations that were specific for each kindred, of which 55 percent had missense mutations and 30 percent had frame-shift mutations; nonsense mutations occurred in 8 percent and splice defects in 4 percent. No correlation between the nature of the mutation and the was detected.
Symptoms
Symptoms of adrenomyelopathy include adrenal dysfunction, trouble controlling urination, muscle weakness or leg stiffness that may worsen over time, and difficulty with visual memory and rapidity of thinking.
Screening and Diagnosis
Laboratory investigation of blood samples may show levels of elevated very-long-chain fatty acids. Peripheral nerve biopsy has revealed characteristic inclusion bodies in the Schwann cells. Chromosome studies can be useful in demonstrating specific gene mutations. Magnetic resonance imaging (MRI) reveals images of damaged white matter in the brain.
Treatment and Therapy
A specific treatment for X-linked adrenoleukodystrophy is not available, but adrenal dysfunction is often treated with steroids such as cortisol. A diet low in very-long-chain fatty acids is thought to lower the blood levels of very-long-chain fatty acids. Ingesting oils, particularly a substance called Lorenzo’s oil, has been used as a treatment for lowering the blood levels of very-long-chain fatty acids. Bone marrow transplant is also considered a potential treatment. Further, stem cell transplant using stem cells harvested through bone marrow transplant may reduce or even stop the progression of adrenoleukodystrophy in children diagnosed and treated at an early stage of the disease.
Prevention and Outcomes
Genetic counseling is recommended for potential parents who have a family history of X-linked adrenoleukodystrophy. A test sensitive in denoting very-long-chain fatty acids and a DNA study by specialized laboratories can diagnose the carrier state in 85 percent of female cases. Prenatal diagnosis of X-linked adrenoleukodystrophy is also available by an amniocentesis. Outcomes of adrenomyelopathy are milder than the childhood form of X-linked adrenoleukodystrophy, which is described as progressive and leads to a long-term coma two years after neurological symptoms develop.
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