Understanding ALD

Understanding ALD

Adrenoleukodystrophy (ALD) is a rare genetic disease that can progress to a serious and life-threatening condition1,2

ALD is a genetic disease caused by mutations in the ABCD1 gene, that results in a deficiency of the peroxisomal protein called adrenoleukodystrophy protein (ALDP). This deficiency leads to the accumulation of very-long chain fatty acids (VLCFAs) in plasma and tissue—primarily of the nervous system and adrenal glands.3

Without early detection, ALD can progress to a serious and life-threatening condition called cerebral ALD.2

DNA with mutations in the ABCD1 gene DNA with mutations in the ABCD1 gene

Test to detect ALD

Measuring VLCFA levels early can help save lives1,5
View Testing Guidelines
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Three steps: Recognize, Measure, and Consult

Pediatric Endocrinologist Bradley Miller touches on the three steps for initial identification and management of ALD

ALD primarily affects males1

Because this disorder results from mutations in a gene on the X chromosome, males are more susceptible—it affects approximately 1 in 21,000 males.1 Although ALD primarily affects males, it is possible for females to develop symptoms of the disease in adulthood.3 There is no evidence that the prevalence of ALD varies with ethnicity.3 ALD consists of a spectrum of phenotypes, which may overlap throughout the lifetime of a patient.4 ALD is a genetic disorder, so once it is diagnosed, it’s important to test other family members, as well.1

Even among members of the same family, it is currently not possible to predict the future phenotype of a boy with ALD without monitoring3

Recognize the link

Adrenal insufficiency is often the first symptom of ALD3,5
up to86%

80% to 86% of boys diagnosed with ALD also have adrenal insufficiency6

While adrenal insufficiency can initially present as early as 5 months of age, on average patients are 4 to 5 years of age at presentation6

80% to 86% of boys diagnosed with ALD also have adrenal insufficiency6

While adrenal insufficiency can initially present as early as 5 months of age, on average patients are 4 to 5 years of age at presentation6

The link between ALD and adrenal insufficiency

Adrenal insufficiency is a prominent symptom of ALD3,5—up to 86% of boys diagnosed with ALD also have adrenal insufficiency.6 Adrenal insufficiency is a rare condition in the general population, often diagnosed in early childhood, in which the adrenal cortex does not function properly.1,5,7

Symptoms may include:5

  • Fatigue
  • Loss of appetite
  • Abdominal pain
  • Hyperpigmentation of skin and/or skin bronzing

Symptoms of ALD often resemble symptoms of other conditions4,8

Because early symptoms of ALD often resemble those of other medical conditions, such as Addison’s disease, there can be difficulty in differential diagnosis.4,8 Further complicating the diagnosis of ALD, the clinical manifestations of the condition can vary widely, even among members of the same family.1 Adrenal insufficiency is often the first sign of ALD.3,5

Identifying cerebral ALD

ALD can also develop into cerebral ALD, a severe, progressive, and life-threatening neurodegenerative form of the disease. Diagnosing cerebral ALD can be difficult as the cognitive symptoms often resemble those of other conditions, such as attention-deficit/hyperactivity disorder (ADHD), autism or other home and school problems, which can delay diagnosis.3,4 This condition often develops between 3 and 12 years, with most patients ranging from 4 to 7 years of age at the time of symptom onset.9,10

In children, cerebral ALD can lead to:7

  • Behavioral or learning issues
  • Cognitive and neurological deficits
  • Severe loss of neurological functions, including impairment of cognition, vision, hearing, and motor function
  • Total disability and death for most patients within 5 years, on average, after the initial onset of symptoms
Torrey family video thumbnail

Torrey family: Recognizing symptoms

Explore the signs and symptoms that led to an ALD diagnosis

ALD can progress to cerebral ALD

40%

ALD can progress to cerebral ALD

Approximately 40% of boys with ALD will develop cerebral ALD.7

In most patients, cerebral ALD is a rapidly progressing disease that causes progressive behavioral, cognitive, and neurological deficits and total disability followed by death, within 5 years after onset of symptoms.7,9

References: 1. Bezman L, Moser AB, Raymond GV, et al. Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol. 2001;49(4):512-517. 2. Miller WP, Rothman SM, Nascene D, et al. Outcomes after allogeneic hematopoietic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118(7):1971-1978. 3. Kemp S, Huffnagel IC, Linthorst GE, Wanders RJ, Engelen M. Adrenoleukodystrophy – neuroendocrine pathogenesis and redefinition of natural history. Nat Rev Endocrinol. 2016;12(10):606-615. 4. Moser HW, Mahmood A, Raymond GV. X‑linked adrenoleukodystrophy. Nat Clin Pract Neurol. 2007;3(3):140-151. 5. Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary Adrenal Insufficiency: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab. 2016;101(2):364-389. 6. Dubey P, Raymond GV, Moser AB, et al. Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening. J Pediatr. 2005;146(4):528-532. 7. Engelen M, Kemp S, Poll-The BT. X‑linked adrenoleukodystrophy: pathogenesis and treatment. Curr Neurol Neurosci Rep. 2014;14(10):486. 8. Laureti S, Casucci G, Santeusanio F, Angeletti G, Aubourg P, Brunetti P. X‑linked adrenoleukodystrophy is a frequent cause of idiopathic Addison’s disease in young adult male patients. J Clin Endocrinol Metab. 1996;81(2):470-474. 9. Mahmood A, Dubey P, Moser HW, et al. X‑linked adrenoleukodystrophy: therapeutic approaches to distinct phenotypes. Pediatr. Transplant. 2005;9 Suppl 7:55-62. 10. Engelen M, Kemp S, de Visser M, et al. X‑linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis. 2012; 7:51.