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Newborn Screening for X-Linked Adrenoleukodystrophy: Review of Data and Outcomes in Pennsylvania

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in <i>ABCD1</i>, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the...

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Main Authors: Jessica R. C. Priestley (Author), Laura A. Adang (Author), Sarah Drewes Williams (Author), Uta Lichter-Konecki (Author), Caitlin Menello (Author), Nicole M. Engelhardt (Author), James C. DiPerna (Author), Brenda DiBoscio (Author), Rebecca C. Ahrens-Nicklas (Author), Andrew C. Edmondson (Author), Francis Jeshira Reynoso Santos (Author), Can Ficicioglu (Author)
Format: Book
Published: MDPI AG, 2022-03-01T00:00:00Z.
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Summary:X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in <i>ABCD1</i>, which encodes the peroxisomal very-long-chain fatty acid transporter, causing a spectrum of neurodegenerative phenotypes. The childhood cerebral form of the disease is particularly devastating. Early diagnosis and intervention improve outcomes. Because newborn screening facilitates identification of at-risk individuals during their asymptomatic period, X-ALD was added to the Pennsylvania newborn screening program in 2017. We analyzed outcomes from the first four years of X-ALD newborn screening, which employed a two-tier approach and reflexive <i>ABCD1</i> sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. <i>ABCD1</i> sequencing identified 21 hemizygous males and 24 heterozygous females, and clinical follow up identified four patients with peroxisomal biogenesis disorders. There were two false-positive cases and one false-negative case. Three unscreened individuals, two of whom were symptomatic, were diagnosed following their young siblings' newborn screening results. Combined with experiences from six other states, this suggests a U.S. incidence of roughly 1 in 10,500, higher than had been previously reported. Many of these infants lack a known family history of X-ALD. Together, these data highlight both the achievements and challenges of newborn screening for X-ALD.
Item Description:10.3390/ijns8020024
2409-515X

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