Newborn Screening for X-Linked Adrenoleukodystrophy: Past, Present, and Future

Abstract

Newborn screening for X-linked adrenoleukodystrophy began in New York in 2013. Prior to this start, there was already significant information on the diagnosis and monitoring of asymptomatic individuals. Methods needed to be developed and validated for the use of dried blood spots. Following its institution in New York, its acceptance as a disorder on the Recommended Uniform Screening occurred. With it has come published recommendations on the surveillance and care of boys detected by newborn screening. There still remain challenges, but it is hoped that with periodic review, they may be overcome.

Age and gender-specific reference intervals for a panel of lysophosphatidylcholines estimated by tandem mass spectrometry in dried blood spots

“…Measurement of 26:0-LysoPC and 24:0-LysoPC in DBS by tandem mass spectrometry has been included [ 20 , 23 ] or is being considered for inclusion in newborn screening panels of many countries [ 16 , 17 , 21 ]. Consequently, appropriate age and gender-specific reference intervals need to be established.…”

“…Recently, newborn screening (NBS) panels have included 26:0- and 24:0-LysoPC to screen for X-ALD along with the other inborn errors of metabolism [ 20 , 22 , 23 ]. To differentiate X-ALD cases from the healthy population, age and gender-specific reference intervals (RIs) and appropriate cut-offs specific to the population of that region are essential [ 24 ].…”

Neurocognitive and mental health impact of adrenoleukodystrophy across the lifespan: Insights for the era of newborn screening

“…The unpredictability of disease course and broad impacts on both the individual and their support system make clinical care challenging. NBS programs are an essential tool to increase early detection of disease manifestations, but adoption of NBS across the United States and other nations continues to progress slowly and there are many complexities to the management of screen‐positive cases 6,110,111 . Evaluation of the success of these early detection efforts will depend on increasing the quality of measurement approaches.…”

“…NBS programs are an essential tool to increase early detection of disease manifestations, but adoption of NBS across the United States and other nations continues to progress slowly and there are many complexities to the management of screen-positive cases. 6,110,111 Evaluation of the success of these early detection efforts will depend on increasing the quality of measurement approaches. Historically, for patients with cerebral ALD, improving survival and freedom from major functional disability were important benchmarks to evaluate therapy relative to the natural history.…”

Current Screening Strategies for the Diagnosis of Adrenal Insufficiency in Children

“…ALD newborn screening has been developed by measuring VLCFA levels in dried blood spots, was first initiated in New York in 2013, added to the Recommended Uniform Screening Panel in 2016. 43 , 47 Currently, newborn screening for ALD has been implemented in 30 states and Washington DC with continuing expansion. Once ALD is diagnosed by newborn screening, all male infants should be referred to pediatric endocrinologists for evaluation for adrenal dysfunction which should be initiated in the first 6 months of life by measuring morning serum cortisol and ACTH levels.…”