Childhood-onset cerebral adrenoleukodystrophy (also known as Cerebral Adrenoleukodystropy, CALD) is a rare X-linked, genetic disorder, affecting boys between 4-10 years old. CALD is caused by a buildup of very long chain fatty acids (VLCFAs). This buildup damages the fatty covering of the nerve and brain cells (myelin). When myelin breaks down, the nervous system has a hard time sending messages.
The first symptom is usually behavior changes like hyperactivity. Symptoms may progress to deafness, blindness, seizures, and loss of muscle control. Excess VLCFAs may also damage the adrenal glands. the damaged adrenal glands don't make enough of the hormones (adrenocortical insufficiency or Addison's disease) causing weakness, weight loss, skin changes and vomiting.
Childhood-onset cerebral adrenoleukodystrophy is caused by a mutation in the ABCD1 gene. This gene makes the ALD protein (ALDP). ALDP helps the peroxisome break down VLCFAs. If there is not enough ALDP, the VCFA’s are not broken down and instead build up. ALD is the most common type of peroxisomal disorder.
Genetic testing of parents and male extended family is mandatory to permit early detection by brain MRI and to propose therapeutic intervention. Systematic testing of women at risk to be carriers is also warranted to propose genetic counseling.
Diagnosis is confirmed by genetic and medical testing, genetic testing must be preceded by testing for high plasma concentrations of VLCFA.
Brain MRI reveals characteristic abnormal white matter signals, often in the splenium or genu of the corpus callosum. Then, the extent of demyelinating lesions progresses, as revealed by peripheral injection of gadolinium.
Left untreated, all but 10% of patients are bedridden, blind, lacking speech and require fulltime care, dying within 2-5 years. Arrested X-CALD may enter a phase of rapid neurological deterioration at any time.
There is now an effective treatment if the changes to myelin in the brain are found before physical symptoms begin. This requires a special brain scan (MRI) to be performed every 6-12 months. Blood tests will be used to check the adrenal gland. Many babies are screened for ALD at birth, but newborn screening conditions vary by state.