Guidance for primary care clinicians receiving a positive newborn screen result

Other Names

ICD-10 Coding

Disorder Category

Abnormal Finding

Tested By

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.

Clinical Characteristics

Incidence

Inheritance

Next Steps After a Positive Screen

• 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.

Confirming the Diagnosis

• To confirm the diagnosis of ALD, contact Newborn Screening Services (see NM providers [3]) to coordinate confirmatory testing.
• 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.

If the Diagnosis is Confirmed

• For evaluation and ongoing collaborative management, consult the specialists recommended by your Newborn Screening Service, which may include Pediatric Neurology (see NM providers [5]) and Pediatric Endocrinology (see NM providers [4]).
• 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.
• 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).
• Although scary, ALD is a treatable disease!
• With close follow-up and care by specialists in ALD, infants, children, and adults can expect to live healthy, productive, and full lives.