Primary adrenal insufficiency (PAI) is a rare condition, often diagnosed in early childhood, in which the adrenal glands do not work properly. The majority of cases of antibody-negative PAI in young boys are caused by adrenoleukodystrophy (ALD)1, 2, 3 , a rare, X-linked disorder resulting from a deficiency in the peroxisomal transporter ALD protein. Some boys with ALD develop a severe, life-threatening neurodegenerative form of the disease known as cerebral ALD or CALD. If CALD is caught early, lifesaving treatment is possible, but early detection is critical. Fortunately, a simple blood test for very long-chain fatty acids (VLCFAs) can diagnose ALD.
Adrenoleukodystrophy (ALD) is a rare, X-linked genetic disorder resulting from a mutation in the ABCD1 gene that encodes for the ALD protein (ALDP). ALDP helps transport very long-chain fatty acids (VLCFAs) to cellular peroxisomes for degradation. ALDP deficiency leads to the accumulation of VLCFAs, primarily in the adrenal cortex and the central nervous system (CNS)3. Between 30% - 40% of boys with ALD will develop the inflammatory cerebral form, CALD, which leads to irreparable, progressive demyelination and neurodegeneration. Boys with CALD may initially exhibit non-specific symptoms of hyperactivity, visual or auditory problems, impaired coordination or seizures. Without treatment, these boys rapidly lose neurological function, often leading to death within 2 to 3 years.3 Early diagnosis of ALD and close monitoring for the development of neurologic symptoms can help save lives.
The most common cause of primary adrenal insufficiency (PAI) is autoimmune disease, diagnosed by 21-hydroxylase antibody testing. The majority of cases of antibody-negative PAI are caused by ALD1, 2, 3. In boys with ALD, elevated VLCFA levels in the adrenal glands lead to adrenal insufficiency. For many boys, adrenal insufficiency is the first detected symptom of ALD. Therefore, if young boys with PAI are antibody-negative, a simple VLCFA blood test should be performed as recommended in the Endocrine Society’s current Clinical Practice Guideline for the diagnosis and treatment of PAI. Identifying ALD early allows for treatment of adrenal insufficiency and close monitoring for the potential development of CALD.
|Preferred specimen||1 mL plasma collected in an EDTA (lavender-top) tube|
|Collection instructions||Fasting sample required|
|Speciment stability||14 days (frozen)|
|Methodology||Gas chromatography-mass spectrometry (GC-MS)|
|Codes and information accurate for Quest Diagnostics screening library.|
Treatment of CALD can be effective and even lifesaving, but only if administered early in the course of cerebral disease before irreparable neurodegeneration has occurred. Once ALD is diagnosed, affected boys can be monitored regularly with MRI to detect cerebral involvement as soon as it develops, and treatment can begin4. Therefore it is critical to diagnose ALD early by following up on common symptoms such as antibody-negative PAI.
The current standard treatment for boys with early-stage CALD is allogeneic hematopoietic cell transplant (HCT)4. Five-year survival rates close to 90% have been reported when HCT is performed early in the course of the disease. When transplant is done later, five-year survival is only 60%5. Although it may be challenging to find an appropriate donor, early diagnosis gives boys with CALD the best chance at positive long-term outcomes. Testing boys with antibody-negative PAI using the VLCFA blood test is a key tool in early diagnosis of ALD.
ItMightBeALD.org is an educational collaboration between ALD Connect, ALD Life, Australasian Leukodystrophy Foundation, Brian’s Hope, Fight ALD to help accelerate the diagnosis of ALD. The initiative is sponsored by bluebird bio®. Together, these organizations are committed to saving lives by raising awareness among physicians, advocating for newborn screening and VLCFA testing, and supporting caregivers. Access the resources below to find out more about the VLCFA assay and how early diagnosis of ALD can save lives.