2023 ACMG Annual Clinical Genetics Meeting Digital Edition: Poster Gallery-X-linked Adrenoleukodystrophy After Implementation of Newborn Screening: A Reference Laboratory Perspective

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X-linked adrenoleukodystrophy (X-ALD) is a genetic disorder caused by a mutation in the ABCD1 gene. This mutation leads to the accumulation of very long-chain fatty acids (VLCFA) and can result in a severe form of the disease called childhood cerebral adrenoleukodystrophy (CCALD). Newborn screening (NBS) for X-ALD has been implemented in 35 states in the United States to detect the disease before symptoms develop and allow for early intervention. <br /><br />A retrospective analysis of plasma samples sent to the ARUP Laboratories for VLCFA testing over a 10-year period was conducted to evaluate the impact of NBS on X-ALD detection. The results showed that the inclusion of X-ALD in NBS programs significantly increased the number of patients detected before symptoms developed. Of the 18,600 samples analyzed, 4.6% had results consistent with a peroxisomal disorder, including X-ALD. After the implementation of NBS for X-ALD, the number of abnormal results doubled. <br /><br />Patients with abnormal results were predominantly males and younger compared to all samples submitted. Most of the abnormal results were diagnostic for X-ALD, while a smaller proportion were indicative of other peroxisomal disorders. Among the patients diagnosed with X-ALD, those identified through NBS were mostly referred because of a positive NBS result in the proband or a family member. Clinical findings and family history were also indications for referral.<br /><br />In conclusion, the implementation of NBS for X-ALD has significantly improved the detection of the disease before symptoms develop. This allows for early intervention and the prevention of severe forms of the disease. The analysis of plasma samples submitted for VLCFA testing provides valuable insights into the impact of NBS on X-ALD detection and highlights the importance of early diagnosis.

Asset Subtitle

Presenting Author - Julia Prinzi, BS; Co-Author - Marzia Pasquali, PhD; Co-Author - Rachel Palmquist, MS, CGC; Co-Author - Kristen N. Wong, MS, CGC; Co-Author - Stephanie Francis, MS, CGC; Submitter Only - Irene De Biase;

Meta Tag

Biochemical genetics

Brain/Nervous System

Metabolic Disorder

X-Inactivation/X-Linked Disease

Co-Author Marzia Pasquali, PhD

Co-Author Rachel Palmquist, MS, CGC

Co-Author Kristen N. Wong, MS, CGC

Co-Author Stephanie Francis, MS, CGC

Presenting Author Julia Prinzi, BS

Submitter Only Irene De Biase

Keywords

X-linked adrenoleukodystrophy

X-ALD

genetic disorder

ABCD1 gene

VLCFA

childhood cerebral adrenoleukodystrophy

newborn screening

NBS

early intervention

plasma samples