Close
Close

Childhood-onset cerebral X-linked adrenoleukodystrophy

Cerebral Adrenoleukodystrophy, CALD, Adrenoleukodystrophy childhood cerebral form, ALD childhood cerebral form, Childhood cerebral ALD, Adrenoleukodystrophy X-linked cerebral form, X-linked cerebral adrenoleukodystrophy

Overview

Childhood-onset cerebral adrenoleukodystrophy 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. 

Symptoms - Childhood-onset cerebral X-linked adrenoleukodystrophy

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.

Causes - Childhood-onset cerebral X-linked adrenoleukodystrophy

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.

Prevention - Childhood-onset cerebral X-linked adrenoleukodystrophy

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 - Childhood-onset cerebral X-linked adrenoleukodystrophy

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.

Prognosis - Childhood-onset cerebral X-linked adrenoleukodystrophy

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.

Treatment - Childhood-onset cerebral X-linked adrenoleukodystrophy

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.

Resources - Childhood-onset cerebral X-linked adrenoleukodystrophy

  • NIH
Videos