Symptoms
Symptoms vary depending on the type and severity of ALD.
Childhood Cerebral ALD (CCALD): Behavioral problems (aggression, withdrawal), vision problems, learning difficulties, difficulty understanding speech, coordination problems, muscle weakness, seizures, and progressive loss of cognitive function.
Adrenomyeloneuropathy (AMN): This adult-onset form primarily affects the spinal cord. Symptoms include stiffness and weakness in the legs, bladder and bowel dysfunction, sexual dysfunction, and sensory loss. Cognitive problems can also develop later.
Adrenal Insufficiency (Addison's Disease): Weakness, fatigue, weight loss, skin darkening, nausea, vomiting, and low blood pressure. This can occur in all forms of ALD.
Causes
ALD is caused by mutations in the ABCD1 gene, which is located on the X chromosome. Because it's X-linked, males (who have one X chromosome) are more severely affected. Females (who have two X chromosomes) can be carriers and may develop milder symptoms later in life. The mutated gene leads to a deficiency in the ALD protein (ALDP), hindering the transport of VLCFAs into peroxisomes for breakdown. This causes VLCFAs to accumulate in tissues, leading to inflammation and damage, particularly in the brain, spinal cord, and adrenal glands.
Medicine Used
Lorenzo's Oil: A mixture of glyceryl trioleate and glyceryl trierucate oils. It can lower VLCFA levels in the blood but has not been shown to reverse neurological damage. Its effectiveness in preventing the onset of CCALD in asymptomatic boys is still debated.
Adrenal Hormone Replacement: For adrenal insufficiency, hormone replacement therapy (usually hydrocortisone or prednisone) is necessary.
Disease-Modifying Therapies: Hematopoietic stem cell transplantation (HSCT) and gene therapy can be used to treat CCALD if detected early. These therapies aim to replace the defective bone marrow cells with healthy ones, preventing further neurological damage.
Symptomatic Treatment: Medications for seizures, spasticity, and other symptoms are used to manage the condition.
Is Communicable
No, ALD is not communicable. It is a genetic disorder inherited from parents. It cannot be spread through contact with an affected individual.
Precautions
Genetic Counseling: Families with a history of ALD should seek genetic counseling to understand the risk of inheritance.
Newborn Screening: Newborn screening for ALD is recommended for early detection in males.
Regular Monitoring: Individuals diagnosed with ALD or who are carriers should undergo regular monitoring for symptoms, including neurological exams, MRI scans, and adrenal function tests.
Prompt Treatment: If CCALD is diagnosed early, prompt treatment with HSCT or gene therapy is crucial to prevent severe neurological damage.
How long does an outbreak last?
ALD is not an infectious disease, so the term "outbreak" does not apply. Instead, ALD is a genetic condition with varying disease progression depending on the form and individual.
CCALD: Progresses rapidly, often over months to a few years if untreated.
AMN: Progresses more slowly, often over decades.
Adrenal Insufficiency: A chronic condition requiring lifelong management.
How is it diagnosed?
Blood Test: Elevated levels of very long-chain fatty acids (VLCFAs) in the blood are a key diagnostic indicator.
Genetic Testing: Confirms the diagnosis by identifying mutations in the ABCD1 gene.
MRI of the Brain: Used to assess the extent of demyelination (damage to the myelin sheath) in the brain, particularly in CCALD.
Adrenal Function Tests: Assess the function of the adrenal glands. ACTH stimulation test is used to assess the adrenal glands' ability to produce cortisol.
Newborn Screening: Screening programs can detect elevated VLCFA levels in newborns.
Timeline of Symptoms
CCALD: Symptoms typically appear between the ages of 4 and 10 but can vary. Initial symptoms often include behavioral changes, followed by vision and motor problems. Without treatment, the disease progresses rapidly.
AMN: Symptoms usually begin in adulthood (20s-50s) with progressive stiffness and weakness in the legs. Bladder, bowel, and sexual dysfunction may follow. Cognitive decline can occur later.
Adrenal Insufficiency: Can occur at any age. Symptoms include fatigue, weakness, weight loss, and skin darkening. Can be the first symptom of ALD in some individuals.
Important Considerations
Early Detection is Key: Newborn screening and early diagnosis are crucial for timely intervention, especially for CCALD, as HSCT or gene therapy can prevent or slow disease progression.
Lifelong Monitoring: Individuals with ALD or who are carriers require lifelong monitoring for the development of symptoms and complications.
Multidisciplinary Care: Management of ALD requires a multidisciplinary approach involving neurologists, endocrinologists, geneticists, neuropsychologists, and other specialists.
Carrier Testing: Female relatives of affected individuals should undergo carrier testing to determine their risk of having affected children.
Family Support: ALD can have a significant impact on families. Support groups and counseling can provide emotional support and resources.