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9 pages, 247 KiB

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Newborn Screening for X-Linked Adrenoleukodystrophy in Nebraska: Initial Experiences and Challenges

by Craig V. Baker, Alyssa Cady Keller, Richard Lutz, Karen Eveans, Krystal Baumert, James C. DiPerna and William B. Rizzo

Int. J. Neonatal Screen. 2022, 8(2), 29; https://doi.org/10.3390/ijns8020029 - 26 Apr 2022

Cited by 11 | Viewed by 3670

Abstract

X-linked adrenoleukodystrophy (X-ALD) is a neurodegenerative disease caused by pathogenic variants in ABCD1 resulting in defective peroxisomal oxidation of very long-chain fatty acids. Most male patients develop adrenal insufficiency and one of two neurologic phenotypes: a rapidly progressive demyelinating disease in mid-childhood (childhood cerebral X-ALD, ccALD) or an adult-onset spastic paraparesis (adrenomyeloneuropathy, AMN). The neurodegenerative course of ccALD can be halted if patients are treated with hematopoietic stem cell transplantation at the earliest onset of white matter disease. Newborn screening for X-ALD can be accomplished by measuring C26:0-lysophosphatidylcholine in dried blood spots. In Nebraska, X-ALD newborn screening was instituted in July 2018. Over a period of 3.3 years, 82,920 newborns were screened with 13 positive infants detected (4 males, 9 females), giving a birth prevalence of 1:10,583 in males and 1:4510 in females. All positive newborns had DNA variants in ABCD1. Lack of genotype-phenotype correlations, absence of predictive biomarkers for ccALD or AMN, and a high proportion of ABCD1 variants of uncertain significance are unique challenges in counseling families. Surveillance testing for adrenal and neurologic disease in presymptomatic X-ALD males will improve survival and overall quality of life. Full article

(This article belongs to the Special Issue Newborn Screening and Follow-Up for X-ALD)

15 pages, 648 KiB

Open AccessArticle

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

by Jessica R. C. Priestley, Laura A. Adang, Sarah Drewes Williams, Uta Lichter-Konecki, Caitlin Menello, Nicole M. Engelhardt, James C. DiPerna, Brenda DiBoscio, Rebecca C. Ahrens-Nicklas, Andrew C. Edmondson, Francis Jeshira Reynoso Santos and Can Ficicioglu

Int. J. Neonatal Screen. 2022, 8(2), 24; https://doi.org/10.3390/ijns8020024 - 23 Mar 2022

Cited by 20 | Viewed by 6069

Abstract

X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder. It results from pathogenic variants in ABCD1, 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 ABCD1 sequencing. There were 51 positive screens with elevated C26:0-lysophosphatidylcholine on second-tier screening. ABCD1 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. Full article

(This article belongs to the Special Issue Newborn Screening and Follow-Up for X-ALD)

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17 pages, 2976 KiB

Open AccessArticle

Newborn Screening for Pompe Disease: Pennsylvania Experience

by Can Ficicioglu, Rebecca C. Ahrens-Nicklas, Joshua Barch, Sanmati R. Cuddapah, Brenda S. DiBoscio, James C. DiPerna, Patricia L. Gordon, Nadene Henderson, Caitlin Menello, Nicole Luongo, Damara Ortiz and Rui Xiao

Int. J. Neonatal Screen. 2020, 6(4), 89; https://doi.org/10.3390/ijns6040089 - 13 Nov 2020

Cited by 34 | Viewed by 5575

Abstract

Pennsylvania started newborn screening for Pompe disease in February 2016. Between February 2016 and December 2019, 531,139 newborns were screened. Alpha-Glucosidase (GAA) enzyme activity is measured by flow-injection tandem mass spectrometry (FIA/MS/MS) and full sequencing of the GAA gene is performed as a second-tier test in all newborns with low GAA enzyme activity [<2.10 micromole/L/h]. A total of 115 newborns had low GAA enzyme activity and abnormal genetic testing and were referred to metabolic centers. Two newborns were diagnosed with Infantile Onset Pompe Disease (IOPD), and 31 newborns were confirmed to have Late Onset Pompe Disease (LOPD). The incidence of IOPD + LOPD was 1:16,095. A total of 30 patients were compound heterozygous for one pathogenic and one variant of unknown significance (VUS) mutation or two VUS mutations and were defined as suspected LOPD. The incidence of IOPD + LOPD + suspected LOPD was 1: 8431 in PA. We also found 35 carriers, 15 pseudodeficiency carriers, and 2 false positive newborns. Full article

(This article belongs to the Special Issue Newborn Screening for Pompe Disease)

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