Adrenoleukodystrophy (ALD)
Screening
Overview
ALD is a disease affecting the brain, spinal cord, and endocrine (adrenal) system. In boys, ALD can cause adrenal insufficiency (Addison’s disease) and, potentially, sudden onset of brain demyelination leading to death. In men and women, ALD can also lead to a slowly progressive disease with chronic neuropathy. ALD is in several different disease category types, including a leukodystrophy, a peroxisomal disorder, an inborn error of metabolism, or an endocrine disease (due to the adrenal insufficiency that can develop).ALD is characterized by accumulation of very long-chain fatty acids (VLCFAs) primarily affecting the adrenal cortex and white matter of the brain and spinal cord. Three variants of X-ALD are categorized by clinical presentation: a childhood cerebral form that occurs primarily in males, adrenomyeloneuropathy (AMN), and Addison-only disease. Females can develop AMN, but the onset is typically later and milder than in affected males. The most debilitating presentation (cALD; cerebral ALD) occurs in males about 4-10 years old with newly-noted attention deficit hyperactivity disorder, followed by progressive cognitive and behavioral decline, adrenal impairment, and characteristic changes on MRI that reflect a demyelinating process.
Prompt follow-up with a specialist after a positive newborn screen is critical because cALD is treatable, but only if therapy is started with the earliest signs of disease. Boys with ALD are typically seen and have brain MRIs twice per year.
Incidence
The incidence of ALD is approximately 1:15,000 live births.Penetrance: Nearly 100% of males have neurologic symptoms by adulthood. Females do not usually present with neurological symptoms until adulthood.
Prenatal Testing
Prenatal testing is available for the genetic cause of ALD, the affected gene known as ABCD1. Prenatal testing should be done with a specialist (perinatologist), and only in cases where there is a known family history.Clinical Characteristics
There are 4 main ways ALD can manifest:- Asymptomatic: ALD without signs or symptoms
- Adrenal insufficiency: ALD that results in adrenal symptoms such as fatigue, loss of appetite, hyperpigmentation (skin darkening), and belly pain. Most boys with ALD will eventually develop adrenal insufficiency. Although adrenal insufficiency is manageable, it can become life-threatening if it is not detected early.
- Adrenomyeloneuropathy (AMN): ALD that commonly starts in adulthood and affects the spinal cord and nerves
- Cerebral ALD: ALD that progresses to affect the brain. The condition can progress very quickly, so early diagnosis and continued monitoring are essential.
With treatment
Hematopoietic stem cell therapy (HSCT) is the only treatment for males with cALD, but it has to be done in the earliest stages to be effective. Corticosteroid replacement is used for the adrenal insufficiency.
Without treatment
Without treatment, boys can develop adrenal insufficiency, which at its most severe can be life-threatening. Without monitoring using MRIs and, if positive, then immediate HSCT, boys who develop cALD will have progressive neurological degeneration leading to death.
Follow-up Testing after Positive Screen
Newborn screening for ALD is very sensitive (>95%) and specific. The false-positive rate is >0.01%.Following confirmation of the elevated VLCFAs, the baby should be referred to a specialist for confirmatory testing, which may include repeating VLCFA levels, endocrine testing, and genetic testing for ABCD1 and its variants.
Once a diagnosis is confirmed, endocrine testing is completed. Then, long-term care requires a specialist team and testing on a repeating basis (endocrine testing and brain MRIs for males).
However, after confirmation of ALD, close follow-up is important; it is not possible to predict what type (fast or slow disease progression) of ALD the infant will have.
Primary Care Management
Upon Notification of the + Screen
- Contact the Newborn Screening Services (see RI providers [1]) to coordinate confirmatory testing.
- Contact the family to ensure that the baby is doing well and to help them understand the testing, condition, and confirmatory testing plan.
- Inquire about a family history of ALD or individuals with signs/symptoms consistent with ALD.
- For evaluation and ongoing collaborative management, consult the specialists recommended by your Newborn Screening Service.
Specialty Care Collaboration
Children diagnosed with ALD should be cared for by a team of neurologists, endocrinologists, and other specialists as needed.Resources
Information & Support
For Parents and Patients
ALD Connect
A non-profit organization focused on improving the quality of life for those living with adrenoleukodystrophy. Initiatives
include advocating for newborn screening, funding research, providing financial support to low-income families, and promoting
education.
United Leukodystrophy Foundation (ULF)
A non-profit organization dedicated to funding cutting-edge research and providing patients and their families with disease
information and medical referrals.
ALD Alliance
Helps families understand a new diagnosis of adrenoleukodystrophy (ALD) by giving them the resources they need to fight this
rare and devastating disease.
Hunter’s Hope/Leukodystrophy Care Network
Established to address the acute need for information and research with respect to leukodystrophies and also support and encourage
those afflicted and their families.
Navigating ALD
Information for those with ALD and their caregivers about about building a care team, managing adrenal insufficiency, monitoring
for cerebral ALD, and exploring treatment.
Practice Guidelines
Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJ, Aubourg P, Poll-The BT.
X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management.
Orphanet J Rare Dis.
2012;7:51.
PubMed abstract / Full Text
Regelmann MO, Kamboj MK, Miller BS, Nakamoto JM, Sarafoglou K, Shah S, Stanley TL, Marino R.
Adrenoleukodystrophy: Guidance for Adrenal Surveillance in Males Identified by Newborn Screen.
J Clin Endocrinol Metab.
2018;103(11):4324-4331.
PubMed abstract / Full Text
Patient Education
A Parent’s Guide; A Guide to Living with ALD (Adrenoleukodystrophy)
Provides support and guidance for parents of children with ALD to help manage the condition and give children the best quality
of life possible.
Living with Leukodystrophy: A Guide for Caring for Leukodystrophy Patients
E-book produced by Cure MLD for caregivers, nurses, and doctors; free to download by using the code provided on webpage.
Services for Patients & Families in Rhode Island (RI)
| Service Categories | # of providers* in: | RI | NW | Other states (5) (show) | | ID | MT | NM | NV | UT |
|---|---|---|---|---|---|---|---|---|---|---|
| Newborn Screening Services | 1 | 1 | 22 | 4 | 2 | 2 | 3 | |||
| Pediatric Endocrinology | 14 | 1 | 2 | 15 | 29 | 6 | 5 | |||
| Pediatric Neurology | 14 | 1 | 15 | 31 | 6 | 6 | ||||
For services not listed above, browse our Services categories or search our database.
* number of provider listings may vary by how states categorize services, whether providers are listed by organization or individual, how services are organized in the state, and other factors; Nationwide (NW) providers are generally limited to web-based services, provider locator services, and organizations that serve children from across the nation.
Studies
Global Leukodystrophy Initiative
A shared research infrastructure supports collection and analysis of robust clinical data and biological specimen to pave
the way for transformative therapeutic trials across the leukodystrophies.
University of Utah/Primary Children’s Leukodystrophy Studies
Established in 2004, the pediatric leukodystrophy center has cared for and treated hundreds of children and adults with leukodystrophies
from all over the country and internationally.