Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Orphanet Journal of Rare Diseases
Published in: Orphanet Journal of Rare Diseases 1/2018

Open Access 01-12-2018 | Research

Economic impact of screening for X-linked Adrenoleukodystrophy within a newborn blood spot screening programme

Authors: Alice Bessey, James B Chilcott, Joanna Leaviss, Anthea Sutton

Published in: Orphanet Journal of Rare Diseases | Issue 1/2018

Login to get access

Abstract

Background

A decision tree model was built to estimate the economic impact of introducing screening for X-linked adrenoleukodystrophy (X-ALD) into an existing tandem mass spectrometry based newborn screening programme. The model was based upon the UK National Health Service (NHS) Newborn Blood Spot Screening Programme and a public service perspective was used with a lifetime horizon. The model structure and parameterisation were based upon literature reviews and expert clinical judgment. Outcomes included health, social care and education costs and quality adjusted life years (QALYs). The model assessed screening of boys only and evaluated the impact of improved outcomes from hematopoietic stem cell transplantation in patients with cerebral childhood X-ALD (CCALD). Threshold analyses were used to examine the potential impact of utility decrements for non-CCALD patients identified by screening.

Results

It is estimated that screening 780,000 newborns annually will identify 18 (95%CI 12, 27) boys with X-ALD, of whom 10 (95% CI 6, 15) will develop CCALD. It is estimated that screening may detect 7 (95% CI 3, 12) children with other peroxisomal disorders who may also have arisen symptomatically. If results for girls are returned an additional 17 (95% CI 12, 25) cases of X-ALD will be identified. The programme is estimated to cost an additional £402,000 (95% CI £399–407,000) with savings in lifetime health, social care and education costs leading to an overall discounted cost saving of £3.04 (95% CI £5.69, £1.19) million per year. Patients with CCALD are estimated to gain 8.5 discounted QALYs each giving an overall programme benefit of 82 (95% CI 43, 139) QALYs.

Conclusion

Including screening of boys for X-ALD into an existing tandem mass spectrometry based newborn screening programme is projected to reduce lifetime costs and improve outcomes for those with CCALD. The potential disbenefit to those identified with non-CCALD conditions would need to be substantial in order to outweigh the benefit to those with CCALD. Further evidence is required on the potential QALY impact of early diagnosis both for non-CCALD X-ALD and other peroxisomal disorders. The favourable economic results are driven by estimated reductions in the social care and education costs.
Appendix
Available only for authorised users
Literature
1.
Bezman L, Moser HW. Incidence of X-linked adrenoleukodystrophy and the relative frequency of its phenotypes. Am J Med Genet. 1998;76:415–9.CrossRef
2.
Heim P, Claussen M, Hoffmann B, Conzelmann E, Gartner J, Harzer K, et al. Leukodystrophy incidence in Germany. Am J Med Genet. 1997;71:475–8.CrossRef
3.
Bezman L, Moser AB, Raymond GV, Rinaldo P, Watkins PA, Smith KD, et al. Adrenoleukodystrophy: incidence, new mutation rate, and results of extended family screening. Ann Neurol. 2001;49:512–7.CrossRef
4.
Kemp S, Berger J, Aubourg P. X-linked adrenoleukodystrophy: clinical, metabolic, genetic and pathophysiological aspects. Biochim Biophys Acta Mol basis Dis. 2012;1822:1465–74.CrossRef
5.
Engelen M, Kemp S, de Visser M, van Geel BM, Wanders RJ, Aubourg P, et al. X-linked adrenoleukodystrophy (X-ALD): clinical presentation and guidelines for diagnosis, follow-up and management. Orphanet J Rare Dis. 2012;7:51.CrossRef
6.
Engelen M, Barbier M, Dijkstra IME, Schur R, De Bie RMA, Verhamme C, et al. X-linked adrenoleukodystrophy in women: a cross-sectional cohort study. Brain. 2014;137:693–706.CrossRef
7.
Turk BR, Moser AB, Fatemi A. Therapeutic strategies in adrenoleukodystrophy. Wien Med Wochenschr. 2017;167:219–26.CrossRef
8.
Eichler F, Duncan C, Musolino PL, Orchard PJ, De Oliveira S, Thrasher AJ, et al. Hematopoietic stem-cell gene therapy for cerebral Adrenoleukodystrophy. N Engl J Med. 2017;377:1630–8.CrossRef
9.
Miller W, Rothman S, Nascene D, Kivisto T, DeFor T, Ziegler R, et al. Outcomes after allogenic hematopoetic cell transplantation for childhood cerebral adrenoleukodystrophy: the largest single-institution cohort report. Blood. 2011;118:1971–8.CrossRef
10.
Peters C, Charnas LR, Tan Y, Ziegler RS, Shapiro EG, DeFor T, et al. Cerebral X-linked adrenoleukodystrophy: the international hematopoietic cell transplantation experience from 1982 to 1999. Blood. 2004;104:881–8.CrossRef
11.
Mahmood A, Raymond GV, Dubey P, Peters C, Moser HW. Survival analysis of haematopoietic cell transplantation for childhood cerebral X-linked adrenoleukodystrophy: a comparison study. Lancet Neurol. 2007;6:687–92.CrossRef
12.
Kühl JS, Suarez F, Gillet FT, Hemmati PG, Snowden JA, Stadler M, et al. Long-term outcomes of allogeneic haematopoietic stem cell transplantation for adult cerebral X-linked adrenoleukodystrophy. Brain. 2017;140:953–66.CrossRef
13.
Theda C, Gibbons K, DeFor TE, Donohue PK, Golden WC, Kline AD, et al. Newborn screening for X-linked adrenoleukodystrophy: further evidence high throughput screening is feasible. Mol Genet Metab. 2014;111:55–7.CrossRef
14.
Horn MA, Retterstol L, Abdelnoor M, Skjeldal OH, Tallaksen CM. Adrenoleukodystrophy in Norway: high rate of de novo mutations and age-dependent penetrance. Pediatr Neurol. 2013;48:212–9.CrossRef
15.
Hubbard WC, Moser AB, Liu AC, Jones RO, Steinberg SJ, Lorey F, et al. Newborn screening for X-linked adrenoleukodystrophy (X-ALD): validation of a combined liquid chromatography-tandem mass spectrometric (LC-MS/MS) method. Mol Genet Metab. 2009;97:212–20.CrossRef
16.
Vogel B, Bradley S, Adams D, D'Aco K, Erbe R, Fong C, et al. Newborn screening for X-linked adrnoluekodystophy in New York state: diagnostic protocol, surveillance protocol and treatment guidelines. Mol Gen Metab. 2015;114:599–603.CrossRef
17.
Braverman NE, Raymond GV, Rizzo WB, Moser AB, Wilkinson ME, Stone EM, et al. Peroxisome biogenesis disorders in the Zellweger spectrum: an overview of current diagnosis, clinical manifestations, and treatment guidelines. Mol Genet Metab. 2016;117:313–21.CrossRef
18.
Wilson JM, Jungner G. Principles and practice of screening for disease. Public health paper 34. Geneva: WHO; 1968.
19.
20.
National Institute of Health and Care Excellence. Guide to the methods of technology appraisal. London: National Institute of Health and Care Excellence; 2013.
21.
Curtis L. Unit costs of health and social care 2014. Canterbury: Personal Social Services Research Unit, University of Kent; 2014.
22.
23.
24.
25.
Kaltenthaler E, Tappenden P, Paisley S, Squires H. NICE DSU technical support document 13: identifying and reviewing evidence to inform the conceptualisation and population of cost-effectiveness models. 2011. http://​www.​nicedsu.​org.​uk. Accessed 14 Oct 2014.
26.
Bessey A, Chilcott J, Pandor A, Paisley S. The cost-effectiveness of expanding the NHS newborn bloodspot screening Programme to include homocystinuria (HCU), maple syrup urine disease (MSUD), glutaric aciduria type 1 (GA1), isovaleric acidaemia (IVA), and long-chain hydroxyacyl-coa dehydrogenase deficiency (LCHADD). Value Health. 2014;17:A531.CrossRef
27.
Hubbard WC, Moser AB, Tortorelli S, Liu A, Jones D, Moser H. Combined liquid chromatography-tandem mass spectrometry as an analytical method for high throughput screening for X-linked adrenoleukodystrophy and other peroxisomal disorders: preliminary findings. Mol Genet Metab. 2006;89:185–18.CrossRef
28.
Turgeon CT, Moser AB, Mørkrid L, Magera MJ, Gavrilov DK, Oglesbee D, et al. Streamlined determination of lysophosphatidylcholines in dried blood spots for newborn screening of X-linked adrenoleukodystrophy. Mol Genet Metab. 2015;114:46–50.CrossRef
29.
Kirk EP, Fletcher JM, Sharp P, Carey B, Poulos A. X-linked adrenoleukodystrophy: the Australasian experience. Am J Med Genet. 1998;76:420–3.CrossRef
30.
Di Biase A, Salvati S, Avellino C, Cappa M, Bertini E, Moroni I, et al. X-linked adrenoleukodystrophy: first report of the Italian study group. Ital J Neurol Sci. 1998;19:315–9.CrossRef
31.
Jardim LB, da Silva AC, Blank D, Villanueva MM, Renck L, Costa ML, et al. X-linked adrenoleukodystrophy: clinical course and minimal incidence in South Brazil. Brain Dev. 2010;32:180–90.CrossRef
32.
Moser BA, Jones OR, Hubbard CW, Tortorelli S, Orsini JJ, Caggana M, et al. Newborn screening for X-linked Adrenoleukodystrophy. Int J Neonatal Screen. 2016;2:15.CrossRef
33.
Wiesinger C, Eichler FS, Berger J. The genetic landscape of X-linked adrenoleukodystrophy: inheritance, mutations, modifier genes, and diagnosis. Appl Clin Genet. 2015;8:109–21.PubMedPubMedCentral
34.
Moser HW. Adrenoleukodystrophy: phenotype, genetics, pathogenesis and therapy. Brain. 1997;120:1485–508.CrossRef
35.
Pereira FS, Matte U, Habekost CT, de Castilhos RM, El Husny AS, Lourenco CM, et al. Mutations, clinical findings and survival estimates in south American patients with X-linked adrenoleukodystrophy. PLoS One. 2012;7:e34195.CrossRef
36.
Ruiz M, Coll MJ, Pampols T, Giros M. X-linked adrenoleukodystrophy: phenotype distribution and expression of ALDP in Spanish kindreds. Am J Med Genet. 1998;76:424–7.CrossRef
37.
Sereni C, Paturneau-Jouas M, Aubourg P, Baumann N, Feingold J. Adrenoleukodystrophy in France: an epidemiological study. Neuroepidemiology. 1993;12:229–33.CrossRef
38.
Takemoto Y, Suzuki Y, Tamakoshi A, Onodera O, Tsuji S, Hashimoto T, et al. Epidemiology of X-linked adrenoleukodystrophy in Japan. J Hum Genet. 2002;47:590–3.CrossRef
39.
Van Geel BM, Assies J, Weverling GJ, Barth PG. Predominance of the adrenomyeloneuropathy phenotype of X-linked adrenoleukodystrophy in the Netherlands: a survey of 30 kindreds. Neurology. 1994;44:2343–6.CrossRef
40.
De Beer M, Engelen M, Van Geel BM. Frequent occurrence of cerebral demyelination in adrenomyeloneuropathy. Neurology. 2014;83:2227–31.CrossRef
41.
Cox CS, Dubey P, Raymond GV, Mahmood A, Moser AB, Moser HW. Cognitive evaluation of neurologically asymptomatic boys with X-linked adrenoleukodystrophy. Arch Neurol. 2006;63:69–73.CrossRef
42.
Dubey P, Raymond GV, Moser AB, Kharkar S, Bezman L, Moser HW. Adrenal insufficiency in asymptomatic adrenoleukodystrophy patients identified by very long-chain fatty acid screening. J Pediatr. 2005;146:528–32.CrossRef
43.
Kaga M, Furushima W, Inagaki M, Nakamura M. Early neuropsychological signs of childhood adrenoleukodystrophy (ALD). Brain Dev. 2009;31:558–61.CrossRef
44.
Keller JL, Wang JI, Kang JY, Hanson JA, Kamath P, Swain JO, et al. Strength: a relevant link to functional performance in the neurodegenerative disease of adrenomyeloneuropathy. Neurorehabil Neural Repair. 2012;26:1080–8.CrossRef
45.
Liang JS, Lee WT, Hwu WL, Peng SS, Chu LW, Wang PJ, et al. Adrenoleukodystrophy: clinical analysis of 9 Taiwanese children. Acta Paediatr Taiwan. 2004;45:272–7.PubMed
46.
Moser HW, Bezman L, Lu SE, Raymond GV. Therapy of X-linked adrenoleukodystrophy: prognosis based upon age and MRI abnormality and plans for placebo-controlled trials. J Inherit Metab Dis. 2000;23:273–7.CrossRef
47.
Stephenson DJ, Bezman L, Raymond GV. Acute presentation of childhood adrenoleukodystrophy. Neuropediatrics. 2000;31:293–7.CrossRef
48.
Suzuki Y, Takemoto Y, Shimozawa N, Imanaka T, Kato S, Furuya H, et al. Natural history of X-linked adrenoleukodystrophy in Japan. Brain Dev. 2005;27:353–7.CrossRef
49.
Walterfang MA, O'Donovan J, Fahey MC, Velakoulis D. The neuropsychiatry of adrenomyeloneuropathy. Cns Spectrums. 2007;12:696–701.CrossRef
50.
Winstone A, Stellitano L, Verity C. The presentation and diagnosis of UK children with X-lined adrenoluekodystrophy ascertained over 17 years. Dev Med Child Neurol. 2015;57:2.
51.
Zachowski K, Dubey P, Raymond G, Mori S, Bastian A. Sensorimotor function and axonal integrity in adrenalmyeloneuropathy. Arch Neurol. 2006;63:74–80.CrossRef
52.
Baumann M, Korenke GC, Weddige-Diedrichs A, Wilichowski E, Hunneman DH, Wilken B, et al. Haematopoietic stem cell transplantation in 12 patients with cerebral X-linked adrenoleukodystrophy. Eur J Pediatr. 2003;162:6–14.CrossRef
53.
Beam D, Poe MD, Provenzale JM, Szabolcs P, Martin PL, Prasad V, et al. Outcomes of unrelated umbilical cord blood transplantation for X-linked adrenoleukodystrophy. Biol Blood Marrow Transplant. 2007;13:665–74.CrossRef
54.
Gassas A, Raiman J, White L, Schechter T, Clarke J, Doyle J. Long-term adaptive functioning outcomes of children with inherited metabolic and genetic diseases treated with hematopoietic stem cell transplantation in a single large pediatric center: parents’ perspective. J Pediatr Hematol Oncol. 2011;33:216–20.CrossRef
55.
Gess A, Christiansen SP, Pond D, Peters C. Predictive factors for vision loss after hematopoietic cell transplant for X-linked adrenoleukodystrophy. J AAPOS. 2008;12:273–6.CrossRef
56.
Loes DJ, Stillman AE, Hite S, Shapiro E, Lockman L, Latchaw RE, et al. Childhood cerebral form of adrenoleukodystrophy: short-term effect of bone marrow transplantation on brain MR observations. AJNR Am J Neuroradiol. 1994;15:1767–71.PubMed
57.
Martin PL, Carter SL, Kernan NA, Sahdev I, Wall D, Pietryga D, et al. Results of the cord blood transplantation study (COBLT): outcomes of unrelated donor umbilical cord blood transplantation in pediatric patients with lysosomal and peroxisomal storage diseases. Biol Blood Marrow Transplant. 2006;12:184–94.CrossRef
58.
Petryk A, Polgreen LE, Chahla S, Miller W, Orchard PJ. No evidence for the reversal of adrenal failure after hematopoietic cell transplantation in X-linked adrenoleukodystrophy. Bone Marrow Transplant. 2012;47:1377–8.CrossRef
59.
Prasad V, Mendizabal A, arikh SH, Szabolcs P, Driscoll T, Page K, et al. Unrelated donor umbilical cord blood transplantation for inherited metabolic disorders in 159 pediatric patients from a single center: influence of cellular composition of the graft on transplantation outcomes. Blood. 2008;112:2979–89.CrossRef
60.
Sakata N, Kawa K, Kato K, Yabe H, Yabe M, Nagasawa M, et al. Unrelated donor marrow transplantation for congenital immunodeficiency and metabolic disease: an update of the experience of the Japan marrow donor program. Int J Hematol. 2004;80:174–82.CrossRef
61.
Shapiro E, Krivit W, Lockman L, Jambaque I, Peters C, Cowan M, et al. Long-term effect of bone-marrow transplantation for childhood-onset cerebral X-linked adrenoleukodystrophy. Lancet. 2000;356:713–8.CrossRef
62.
Wilken B, Dechent P, Brockmann K, Finsterbusch J, Baumann M, Ebell W, et al. Quantitative proton magnetic resonance spectroscopy of children with adrenoleukodystrophy before and after hematopoietic stem cell transplantation. Neuropediatrics. 2003;34:237–46.CrossRef
63.
Guyot P, Ades AE, Ouwens MJNM, Welton NJ. Enhanced secondary analysis of survival data: reconstructing the data from published Kaplan-Meier survival curves. BMC Med Res Methodol. 2012;12:9.CrossRef
64.
Latimer N. NICE DSU Technical Support Document 14: Undertaking survival analysis for economic evaluations alongside clinical trials - extrapolation with patient-level data. 2011. http://​www.​nicedsu.​org.​uk. Accessed 23 Mar 2015.
65.
Van Geel BM, Poll-The BT, Verrips A, Boelens JJ, Kemp S, Engelen M. Hematopoietic cell transplantation does not prevent myelopathy in X-linked adrenoleukodystrophy: a retrospective study. J Inherit Metab Dis. 2015;38:359–61.CrossRef
66.
Kind P, Dolan P, Gudex C, Williams A. Variations in population health status: results from a United Kingdom national questionnaire survey. BMJ. 1998;316:736.CrossRef
67.
68.
Kobelt G, Berg J, Lindgren P, Fredrikson S, Jönsson B. Costs and quality of life of patients with multiple sclerosis in Europe. J Neurol Neurosurg Psychiatry. 2006;77:918.CrossRef
69.
70.
71.
Paediatric Formulary Committee. British National Formulary for Children 2014–2015. London: BMJ Group, Pharmaceutical Press, and RCPCH Publications; 2015.
72.
Barrett B, Mosweu I, Jones CRG, Charman T, Baird G, Simonoff E, et al. Comparing service use and costs among adolescents with autism spectum disorders, special needs and typical development. Autism. 2015;19:5.CrossRef
73.
Kobelt G, Berg J, Lindgren P, Kerrigan J, Russel N, Nixon R. Costs and quality of life of multiple sclerosis in the United Kingdom. Eur J Health Econ. 2006;7(Suppl 5):S96–S104.CrossRef
74.
Stevens K. Developing a descriptive system for a new preference-based measure of health-related quality of life for children. Qual Life Res. 2009;18:1105–13.CrossRef
75.
Adlard N, Kinghorn P, Frew E. Is the UK NICE reference case influencing the practice of pediatric quality-adjusted life-year measurement within economic evaluations? Value Health. 2014;17:454–61.CrossRef
76.
Lamsal R, Zwicker JD. Economic evaluation of interventions for children with neurodevelopmental disorders: opportunities and challenges. Appl Health Econ Health Policy. 2017;15:763–72.CrossRef
77.
Beckmann NB, Miller WP, Dietrich MS, Orchard PJ. Quality of life among boys with adrenoleukodystrophy following hematopoietic stem cell transplant. Child Neuropsychol. 2018;24:986–98.CrossRef
78.
Pierpont EI, Eisengart JB, Shanley R. Neurocognitive trajectory of boys who received a hematopoietic stem cell transplant at an early stage of childhood cerebral adrenoleukodystrophy. JAMA Neurol. 2017;74:710–7.CrossRef
79.
Kemper AR, Brosco J, Comeau AM, Green NS, Grosse SD, Jones E, et al. Newborn screening for X-linked adrenoleukodystrophy: evidence summary and advisory committee recommendation. Genet Med. 2016;9:12.
80.
Grosse SD, Rogowski WH, Ross LF, Cornel MC, Dondorp WJ, Khoury MJ. Population screening for genetic disorders in the 21st century: evidence, economics, and ethics. Public Health Genomics. 2010;13:106–15.CrossRef
81.
Langer A, Holle R, John J. Specific guidelines for assessing and improving the methodological quality of economic evaluations of newborn screening. BMC Health Serv Res. 2012;12:300.CrossRef
Metadata
Title
Economic impact of screening for X-linked Adrenoleukodystrophy within a newborn blood spot screening programme
Authors
Alice Bessey
James B Chilcott
Joanna Leaviss
Anthea Sutton
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Orphanet Journal of Rare Diseases / Issue 1/2018
Electronic ISSN: 1750-1172
DOI
https://doi.org/10.1186/s13023-018-0921-4

Other articles of this Issue 1/2018

Orphanet Journal of Rare Diseases 1/2018 Go to the issue

Research

Pathophysiology of carotid-cavernous fistulas in vascular Ehlers-Danlos syndrome: a retrospective cohort and comprehensive review

Research

Impact of biobanks on research outcomes in rare diseases: a systematic review

Position statement

A perspective on “cure” for Rett syndrome

Review

Hearing impairment in MELAS: new prospective in clinical use of microRNA, a systematic review

Research

A nomenclature and classification for the congenital myasthenic syndromes: preparing for FAIR data in the genomic era

Review

Clinical and genetic characteristics of cystic fibrosis in CHINESE patients: a systemic review of reported cases