Adrenomyeloneuropathy (AMN) is a rare hereditary

neurodegenerative disorder A neurodegenerative disease is caused by the progressive loss of neurons, in the process known as neurodegeneration. Neuronal damage may also ultimately result in their death. Neurodegenerative diseases include amyotrophic lateral sclerosis, mul ...

that primarily affects the spinal cord and peripheral nerves, occurring in less than 1 in 40,000 people. It is characterised by progressive motor dysfunction and

adrenal insufficiency Adrenal insufficiency is a condition in which the adrenal glands do not produce adequate amounts of steroid hormones. The adrenal glands—also referred to as the adrenal cortex—normally secrete glucocorticoids (primarily cortisol), mineraloco ...

. AMN is a form of X-linked adrenoleukodystrophy, a peroxisomal disorder caused by mutations in the ''ABCD1'' gene. Symptoms most commonly begin in a person's late twenties. AMN predominantly affects adult males but

heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

females may develop symptoms later in life. Treatments mainly center around symptom-management.

Symptoms

Symptoms of AMN typically begin in adulthood, with the mean onset of symptoms for affected males occurring at 27.6 years of age. Common symptoms include: * Spastic paraparesis (progressive stiffness and weakness of the legs) *

Ataxia Ataxia (from Greek α- negative prefix+ -τάξις rder= "lack of order") is a neurological sign consisting of lack of voluntary coordination of muscle movements that can include gait abnormality, speech changes, and abnormalities in e ...

(loss of coordination) * Neurogenic bladder and

bowel The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascular system. T ...

dysfunction *

Sexual dysfunction Sexual dysfunction is difficulty experienced by an individual or partners during any stage of normal sexual activity, including physical pleasure, desire, preference, arousal, or orgasm. The World Health Organization defines sexual dysfunction ...

* Adrenocortical insufficiency, leading to

fatigue Fatigue is a state of tiredness (which is not sleepiness), exhaustion or loss of energy. It is a signs and symptoms, symptom of any of various diseases; it is not a disease in itself. Fatigue (in the medical sense) is sometimes associated wit ...

weight loss Weight loss, in the context of medicine, health, or physical fitness, refers to a reduction of the total body mass, by a mean loss of fluid, body fat (adipose tissue), or lean mass (namely bone mineral deposits, muscle, tendon, and other conn ...

, and low blood pressure *

Peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...

, causing numbness or pain in the limbs Approximately 46% of males with AMN also experience cerebral involvement, which can result in

cognitive decline Cognitive impairment is an inclusive term to describe any characteristic that acts as a barrier to the cognition process or different areas of cognition. Cognition, also known as cognitive function, refers to the mental processes of how a person ...

, behavioural changes, vision and hearing loss, and

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

Heterozygous Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism. Mos ...

females, though once thought to be asymptomatic carriers, tend to develop

myelopathy Myelopathy describes any neurologic deficit related to the spinal cord. When due to trauma, myelopathy is known as (acute) spinal cord injury. When inflammatory, it is known as myelitis. Disease that is vascular in nature is known as vascular ...

and/or

neuropathy Peripheral neuropathy, often shortened to neuropathy, refers to damage or disease affecting the nerves. Damage to nerves may impair sensation, movement, gland function, and/or organ function depending on which nerve fibers are affected. Neuropa ...

before the age of 60, with the likelihood of symptoms increasing with age. However, only 1% develop adrenocortical insufficiency and 2% experience cerebral involvement.

Causes

AMN is caused by

mutations In biology, a mutation is an alteration in the nucleic acid sequence of the genome of an organism, virus, or extrachromosomal DNA. Viral genomes contain either DNA or RNA. Mutations result from errors during DNA or viral replication, mitosi ...

in the ABCD1 gene on the

X chromosome The X chromosome is one of the two sex chromosomes in many organisms, including mammals, and is found in both males and females. It is a part of the XY sex-determination system and XO sex-determination system. The X chromosome was named for its u ...

. These mutations precipitate the accumulation of very long-chain fatty acids (VLCFAs) within the neuronal myelin sheaths of the spinal cord, brain, adrenal glands, and testes, causing a non-inflammatory

facilitated by

microglia Microglia are a type of glia, glial cell located throughout the brain and spinal cord of the central nervous system (CNS). Microglia account for about around 5–10% of cells found within the brain. As the resident macrophage cells, they act as t ...

l cells. AMN is primarily an axonopathy or neuronopathy, with the spinal cord being the most consistently affected structure.

Diagnosis

Newborn screening tests are important diagnostic markers for this condition.

Blood test A blood test is a medical laboratory, laboratory analysis performed on a blood sample that is usually extracted from a vein in the arm using a hypodermic needle, or via fingerprick. Multiple tests for specific blood components, such as a glucose ...

s are typically the first step and may reveal elevated levels of very long-chain fatty acids ( VLCFAs), a biochemical hallmark of X-linked adrenoleukodystrophy. Genetic testing is then used to confirm the diagnosis by pinpointing mutations in the '' ABCD1'' gene. Magnetic resonance imaging (MRI) and other imaging techniques are used to detect cerebral involvement and continuously monitor the disease's progression. Adrenal function tests (including measurements of

cortisol Cortisol is a steroid hormone in the glucocorticoid class of hormones and a stress hormone. When used as medication, it is known as hydrocortisone. Cortisol is produced in many animals, mainly by the ''zona fasciculata'' of the adrenal corte ...

and adrenocorticotropic hormone) are also used to evaluate adrenal insufficiency.

Treatment

While there is no cure for AMN there exists several treatments to help manage

symptoms Signs and symptoms are diagnostic indications of an illness, injury, or condition. Signs are objective and externally observable; symptoms are a person's reported subjective experiences. A sign for example may be a higher or lower temperature ...

and slow the progression of the disease. For instance,

hormone replacement therapy Hormone replacement therapy (HRT), also known as menopausal hormone therapy or postmenopausal hormone therapy, is a form of hormone therapy used to treat symptoms associated with female menopause. Effects of menopause can include symptoms such ...

uses

glucocorticoid Glucocorticoids (or, less commonly, glucocorticosteroids) are a class of corticosteroids, which are a class of steroid hormones. Glucocorticoids are corticosteroids that bind to the glucocorticoid receptor that is present in almost every vertebra ...

s (such as

hydrocortisone Hydrocortisone is the name for the hormone cortisol when supplied as a medication. It is a corticosteroid and works as an anti-inflammatory and by immune suppression. Uses include conditions such as adrenocortical insufficiency, adrenogenit ...

) and

mineralocorticoid Mineralocorticoids are a class of corticosteroids, which in turn are a class of steroid hormones. Mineralocorticoids are produced in the adrenal cortex and influence salt and water balances (electrolyte balance and fluid balance). The primary ...

s (such as fludrocortisone) to treat adrenal insufficiency. Other approaches such as

physical therapy Physical therapy (PT), also known as physiotherapy, is a healthcare profession, as well as the care provided by physical therapists who promote, maintain, or restore health through patient education, physical intervention, disease preventio ...

help maintain mobility and manage muscle tightness. In recent years

gene therapy Gene therapy is Health technology, medical technology that aims to produce a therapeutic effect through the manipulation of gene expression or through altering the biological properties of living cells. The first attempt at modifying human DNA ...

and

hematopoietic stem cell transplantation Hematopoietic stem-cell transplantation (HSCT) is the transplantation of multipotent hematopoietic stem cells, usually derived from bone marrow, peripheral blood, or umbilical cord blood, in order to replicate inside a patient and produce ...

have become increasingly studied for their potential applications to AMN, particularly for cases with cerebral involvement. Early diagnosis and intervention are crucial for managing AMN and improving patient's quality of life.

Prognosis

The progression of AMN varies greatly among effected individuals as some patients may face a slow decline over decades while others, especially those with cerebral involvement, may face rapid deterioration. Regular monitoring and supportive care are essential to address the evolving needs of individuals with AMN.

References

{{Reflist Neurodegenerative disorders