Evaluation of X-Linked Adrenoleukodystrophy Newborn Screening in North Carolina

Lee, Stacey; Clinard, Kristin; Young, Sarah P.; Rehder, Catherine; Fan, Zheng; Çalıkoğlu, Ali S.; Bali, Deeksha; Bailey, Donald B.; Gehtland, Lisa M.; Millington, David S.; Patel, Hari S.; Beckloff, Sara E.; Zimmerman, Scott J.; Powell, Cynthia M.; Taylor, Jennifer L.

doi:10.1001/jamanetworkopen.2019.20356

Cited by 50 publications

(62 citation statements)

References 23 publications

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“…After our adjusted second tier cutoff, California observed an ALD birth prevalence of 1 in 14,397 males. This compares to a birth prevalence of 1 in 18,783 found in New York state [ 16 ], 1 in 3878 in Minnesota [ 31 ], 1 in 8717 in South Carolina [ 32 ], and 1 in 51,081 in Georgia [ 33 ]. Differences between screening cutoffs, case definitions, and ABCD1 carrier frequencies in our population samples are likely leading to the reported variations in birth prevalence between states.…”

Section: Discussionmentioning

confidence: 73%

Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up

Matteson

Sciortino

Feuchtbaum

et al. 2021

IJNS

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X-linked adrenoleukodystrophy (ALD) is a recent addition to the Recommended Uniform Screening Panel, prompting many states to begin screening newborns for the disorder. We provide California’s experience with ALD newborn screening, highlighting the clinical and epidemiological outcomes observed as well as program implementation challenges. In this retrospective cohort study, we examine ALD newborn screening results and clinical outcomes for 1,854,631 newborns whose specimens were received by the California Genetic Disease Screening Program from 16 February 2016 through 15 February 2020. In the first four years of ALD newborn screening in California, 355 newborns screened positive for ALD, including 147 (41%) with an ABCD1 variant of uncertain significance (VUS) and 95 males diagnosed with ALD. After modifying cutoffs, we observed an ALD birth prevalence of 1 in 14,397 males. Long-term follow-up identified 14 males with signs of adrenal involvement. This study adds to a growing body of literature reporting on outcomes of newborn screening for ALD and offering a glimpse of what other large newborn screening programs can expect when adding ALD to their screening panel.

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Section: Discussionmentioning

confidence: 73%

Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up

Matteson

Sciortino

Feuchtbaum

et al. 2021

IJNS

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“…The screen-positive rate using GlcA-tetrol/t-CDCA ratio as the primary marker is 0.031% and is acceptable for a newborn screening test compared to other active newborn screening programs. 16 – 18 By implementing GlcA-tetrol and t-THCA/GlcA-tetrol as secondary markers, the screen-positive rate can be further reduced, as shown in this study. Vaz et al originally proposed to screen CTX by measuring the GlcA-tetrol/t-CDCA ratio using flow-injection MS/MS without using an internal standard.…”

Section: Discussionmentioning

confidence: 74%

Toward newborn screening of cerebrotendinous xanthomatosis: results of a biomarker research study using 32,000 newborn dried blood spots

Hong

Daiker

Sadı́lek

et al. 2020

Genetics in Medicine

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Purpose Cerebrotendinous xanthomatosis (CTX) is a treatable hereditary disorder caused by the deficiency of sterol 27- hydroxylase, which is encoded by the CYP27A1 gene. Different newborn screening biomarkers for CTX have been described, including 7α,12α-dihydroxy-4-cholesten-3-one ( 7α12αC4 ), 5b-cholestane-3 α, 7α,12α,25-tetrol glucuronide(GlcA-tetrol), GlcA-tetrol to tauro-chenodeoxycholic acid (t-CDCA) ratio (GlcA-tetrol/t-CDCA), and tauro- trihydroxycholestanoic acid (t-THCA) to GlcA-tetrol ratio (t-THCA/GlcA-tetrol ). We set out to evaluate these screening methods in a research study using 32,000–55,000 newborn dried blood spots (DBS). Method Metabolites were extracted from DBS with methanol containing internal standard, which was then quantified by ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Results The measurement of 7α12αC4 was complicated by isobaric interferences and was discontinued after 2,033 samples. A total of 55,250 newborns were screened for the GlcA-tetrol/t-CDCA ratio, 32,737 of which had quantitative data on GlcA-tetrol. Only one newborn displayed both highly elevated GlcA-tetrol and a typical CTX biochemical profile. This newborn was interpreted as a CTX-affected patient as CYP27A1 gene sequencing identified two known pathogenic variants. Conclusion The results indicate that both GlcA-tetrol and GlcA-tetrol/t-CDCA ratio are excellent CTX biomarkers suitable for newborn screening. By characterizing the relationship of GlcA-tetrol, t-CDCA, and t-THCA as secondary markers, 100% assay specificity can be achieved.

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“…Patients are usually asymptomatic at birth; likewise, it is difficult to detect it in female patients who are carriers. This, combined with the potentially deathly progression of CALD, puts X-ALD in an ideal condition for detection in newborns 10 .…”

Section: Discussionmentioning

confidence: 99%

“…Once the patient is identified, sequencing of the ABCD1 gene is requested to confirm diagnosis (Fig. 2) 10,11 . The patient and his/her family are referred to receive counseling; similarly, confirmation tests are performed in all members that may require them, and suprarenal function is assessed.…”

Section: Discussionmentioning

confidence: 99%

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X-linked adrenoleukodystrophy in a pediatric patient: A case report

López-Uriarte¹,

Hinojosa-Amaya²,

Peña-Balboa³

et al. 2021

RMU

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X-linked adrenoleukodystrophy (X-ALD) is a peroxisomal disorder caused by mutations in the ABCD1 gene leading to the accumulation of very long-chain fatty acids. A 6-year-old male started his condition 6 months ago with developmental regression and loss of visual acuity. Physical examination showed hyperpigmentation in the folds and strabismus of the left eye; ophthalmoscopy showed bilateral optic nerve atrophy, decreased osteotendinous reflexes, and ataxic gait. Adrenal function was evaluated, finding elevated adrenocorticotropic hormone (ACTH). It was decided to start hormone replacement therapy, and he was sent to the department of genetics, who started treatment with Lorenzo's oil. He presented an infectious condition requiring hospitalization; 1 week after this event, he attended pediatric endocrinology with new ACTH results showing a poor response to treatment, doses were adjusted. Three months later, he came with a deterioration of symptoms, so a new treatment was started and new studies were requested. The clinical presentation, in this case, is atypical to X-ALD. The progression of the disease is rapid with characteristics similar to MLD, which implies a greater challenge in the diagnosis.

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Evaluation of X-Linked Adrenoleukodystrophy Newborn Screening in North Carolina

Cited by 50 publications

References 23 publications

Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up

Adrenoleukodystrophy Newborn Screening in California Since 2016: Programmatic Outcomes and Follow-Up

Toward newborn screening of cerebrotendinous xanthomatosis: results of a biomarker research study using 32,000 newborn dried blood spots

X-linked adrenoleukodystrophy in a pediatric patient: A case report

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