PAI?
It Might Be
ADRENO-
LEUKO-
DYSTROPHY

Primary adrenal insufficiency (PAI) is a rare condition, often diagnosed in early childhood, in which the adrenal glands do not work properly.1, 2 The symptoms of PAI may include anorexia, fatigue, nausea, vomiting, loss of appetite, poor weight gain or weight loss and hyperpigmentation of the skin.3 Adrenoleukodystrophy (ALD), a rare, X‑linked disorder resulting from a deficiency in the peroxisomal transporter ALD protein (ALDP), is a frequent cause of PAI in boys.2, 4, 5, 6 Some boys with ALD develop a severe, progressive, and 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, early detection can be possible as increased levels of plasma VLCFA are indicative of ALD.2

What is ALD?

Adrenoleukodystrophy (ALD) is a rare, X-linked 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).2 Between 35% - 40% of boys with ALD will develop the inflammatory cerebral form, CALD, which leads to irreparable, progressive demyelination and neurodegeneration. Some boys with CALD may initially exhibit non-specific symptoms of hyperactivity, visual or auditory problems, impaired coordination, or seizures. Without treatment, the disease progresses rapidly leading to severe loss of neurologic function, and ultimately death.2 Early diagnosis of ALD and close monitoring for signs of cerebral demyelination and neurological symptoms can help saves lives.2

ABCD1 gene location on X-chromosome

ALD+Primary Adrenal Insufficiency?

The most common cause of primary adrenal insufficiency (PAI) is autoimmune disease, which can be diagnosed by assessing autoimmune antibodies.1 A significant number of antibody-negative PAI cases are caused by ALD.2, 5 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.7 Therefore, if young boys with PAI are autoantibody-negative, VLCFA levels should be assessed as recommended in the current Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline.1 Identifying ALD early allows for treatment of adrenal insufficiency and close monitoring for the potential development of CALD.2

 


Early Diagnosis Could Save Lives

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.2 Once ALD is diagnosed, it is recommended that affected boys be monitored regularly with a brain MRI to detect cerebral involvement as soon as it develops, and treatment can be considered.2 Therefore it is critical to diagnose ALD early by following up on common symptoms such as autoantibody-negative PAI.1



Measuring plasma VLCFA levels in patients with autoantibody-negative PAI could help save the life of a boy with ALD7

CALD Treatment Depends on Early Diagnosis

Allogeneic stem cell transplantation (allo-HSCT) is effective at arresting disease progression if performed early in the course of cerebral disease.2 Five‑year survival rates close to 90% have been reported when allo-HSCT is performed in boys with early disease. When transplant is done later, five-year survival is only 60%.8 Although it may be challenging to find an appropriate donor9, early diagnosis gives boys with CALD the best chance at positive long-term outcomes. Testing boys with autoantibody-negative PAI by measuring plasma VLCFA levels is a key tool in early diagnosis of ALD.2

Who We Are

This educational initiative is sponsored by bluebird bio®, Inc. bluebird bio would like to thank the patient organizations who provided invaluable time and feedback on the concept of this educational initiative.

 


Research and Resources

bluebird bio, Inc. is not responsible for the content provided by third party sites, nor does bluebird bio, Inc. endorse the content of these sites. Below is not a comprehensive list of resources and it is provided for reference only.

Endocrine Society’s PAI Clinical Practice Guideline

PAI as a Red Flag for ALD

Guidelines for Diagnosis and Clinical Management of X-ALD