for fighting life-altering disease.
CALD is a progressive, irreversible, and fatal disease primarily affecting young children.
Cerebral adrenoleukodystrophy – or CALD – is a rare and devastating neurologic disease that robs young patients of the chance to live a full life. The disease results in rapid loss of neurological function after the initial onset of symptoms and sadly, nearly half of patients who do not receive treatment die within five years of symptom onset.
Adrenoleukodystrophy (ALD) is a rare, X-linked, metabolic disorder caused by a mutation in the ABCD1 gene which results in the toxic buildup of very long-chain fatty acids (VLCFA) in the brain and spinal cord. CALD is the most severe and neurodegenerative form of this condition.
The accumulation of VLCFA in the adrenal cortex and white matter of the brain and spinal cord leads to the progressive destruction of myelin, the protective sheath of the nerve cells in the brain that are responsible for thinking and muscle control. Without myelin, these nerves can no longer relay information to and from the brain.
For many boys, adrenal insufficiency or behavioral problems are the first detected symptoms, preceding the onset of neurologic symptoms. As the disease progresses, boys develop vision and hearing problems, seizures, poor coordination, and difficulty swallowing.
ALD is estimated to affect 1 in 5,000 to 1 in 17,000 newborns (both male and female), and approximately 1 in 20,000 to 1 in 30,000 newborn males. CALD develops in approximately 40% of affected boys and in a smaller number of adult men.
CALD results in rapid loss of function in untreated patients.
There are six major functional disabilities (MFDs) associated with CALD. In untreated patients, MFDs can progress rapidly, and have a catastrophic impact on basic functions:
- loss of communication
- cortical blindness (total or partial loss of vision caused by damage to the brain’s occipital cortex, without any ophthalmological causes)
- tube feeding (nutrition delivered into the stomach with a nasogastric tube, bypassing the mechanisms of chewing and swallowing)
- total incontinence
- wheelchair dependence
- complete loss of voluntary movement
Currently, there is no way to predict which boys with ALD will develop CALD. Fortunately, however, the early stages of CALD can be detected by brain MRI in boys with known ALD, even when they don’t have any noticeable symptoms. Current guidelines recommend that all boys diagnosed with ALD are monitored regularly with MRIs.
The only available therapeutic option for CALD is a stem cell transplant, a procedure in which the patient receives blood stem cells from a genetically matched donor.
There is currently only one therapeutic option available for children with CALD: an allogeneic hematopoietic stem cell transplant (allo-HSCT). This procedure is effective in stabilizing neurologic function, but it is associated with serious potential complications and mortality that increase in patients without a matched sibling donor. It is estimated that more than 70% of patients diagnosed with CALD do not have a matched sibling donor.
Early diagnosis remains a critical factor in managing CALD, and additional treatment options are urgently needed.
There is currently no way to predict which children with ALD will develop CALD. Diagnosing and treating CALD as early as possible is essential to give these children the best possible chance at life by stopping disease progression and preserving neurological function.
Newborn screening for ALD is vital to enable early diagnosis and treatment. In the U.S., newborn screening for ALD was added to the Department of Health and Human Service’s Recommended Universal Screening Panel in 2016 and is being successfully implemented across the country as states adopt this as part of their universal newborn screening programs.
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