Research Publications
Kotes E, Gavazzi F, Woidill S, Sevagamoorthy A, Yang E, Smith V, Dubbs H, Pierce SR, Pucci K, Vithayathil J, Thakur N, Adang LA. Determination of Health Concepts in β-Propeller Protein-Associated Neurodegeneration. J Child Neurol. 2024 Oct 8:8830738241283932. doi: 10.1177/08830738241283932. Epub ahead of print. PMID: 39376195.
β-propeller protein–associated neurodegeneration (BPAN) is a progressive, neurodegenerative disease characterized by buildup of iron in the brain, leading to severe neurologic impairments. Future clinical trials are anticipated to identify new therapies for BPAN.
In this natural history study, researchers characterized family perspectives to define health concepts in BPAN. Among 42 caregivers of children diagnosed with BPAN, the team administered the Vineland Adaptive Behavior Scales, Third Edition—a tool which supports diagnosis of intellectual and developmental disabilities—along with health-related quality of life questionnaires.
Results highlight the effects of BPAN on both patient and caregiver quality of life. Key health concepts identified by families included overall health, comfort, and communication. Authors note that these health concepts will help inform future clinical outcome assessments.
Chen Y, Dawes R, Kim HC, Ljungdahl A, Stenton SL, Walker S, Lord J, Lemire G, Martin-Geary AC, Ganesh VS, Ma J, Ellingford JM, Delage E, D'Souza EN, Dong S, Adams DR, Allan K, Bakshi M, Baldwin EE, Berger SI, Bernstein JA, Bhatnagar I, Blair E, Brown NJ, Burrage LC, Chapman K, Coman DJ, Compton AG, Cunningham CA, D'Souza P, Danecek P, Délot EC, Dias KR, Elias ER, Elmslie F, Evans CA, Ewans L, Ezell K, Fraser JL, Gallacher L, Genetti CA, Goriely A, Grant CL, Haack T, Higgs JE, Hinch AG, Hurles ME, Kuechler A, Lachlan KL, Lalani SR, Lecoquierre F, Leitão E, Fevre AL, Leventer RJ, Liebelt JE, Lindsay S, Lockhart PJ, Ma AS, Macnamara EF, Mansour S, Maurer TM, Mendez HR, Metcalfe K, Montgomery SB, Moosajee M, Nassogne MC, Neumann S, O'Donoghue M, O'Leary M, Palmer EE, Pattani N, Phillips J, Pitsava G, Pysar R, Rehm HL, Reuter CM, Revencu N, Riess A, Rius R, Rodan L, Roscioli T, Rosenfeld JA, Sachdev R, Shaw-Smith CJ, Simons C, Sisodiya SM, Snell P, St Clair L, Stark Z, Stewart HS, Tan TY, Tan NB, Temple SEL, Thorburn DR, Tifft CJ, Uebergang E, VanNoy GE, Vasudevan P, Vilain E, Viskochil DH, et al. De novo variants in the RNU4-2 snRNA cause a frequent neurodevelopmental syndrome. Nature. 2024 Aug;632(8026):832-840. doi: 10.1038/s41586-024-07773-7. Epub 2024 Jul 11.
Ferreira da Silva J, Tou CJ, King EM, Eller ML, Rufino-Ramos D, Ma L, Cromwell CR, Metovic J, Benning FMC, Chao LH, Eichler FS, Kleinstiver BP. Click editing enables programmable genome writing using DNA polymerases and HUH endonucleases. Nat Biotechnol. 2024 Jul 22. doi: 10.1038/s41587-024-02324-x. Online ahead of print.
Nomakuchi TT, Teferedegn EY, Li D, Muirhead KJ, Dubbs H, Leonard J, Muraresku C, Sergio E, Arnold K, Pizzino A, Skraban CM, Zackai EH, Wang K, Ganetzky RD, Vanderver AL, Ahrens-Nicklas RC, Bhoj EJK. Utility of genome sequencing in exome-negative pediatric patients with neurodevelopmental phenotypes. Am J Med Genet A. 2024 Jul 19:e63817. doi: 10.1002/ajmg.a.63817. Epub ahead of print. PMID: 39031459.
Neurodevelopmental disorders have a wide range of causes, which can lead to diagnostic challenges. Patients are often subjected to a long course of tests with frequently inconclusive results. Exome sequencing is a comprehensive genetic test that can help evaluate undiagnosed neurodevelopmental disorders. However, these tests may miss rare diagnoses due to technical limitations. While genome sequencing addresses many of these limitations, it is less commonly used due to higher cost and more intense analysis.
In this study, researchers illustrate the diagnostic utility of genome sequencing in pediatric cases of neurodevelopmental disorders following non-diagnostic exome sequencing. The team describes nine cases of individuals presenting with global developmental delay or regression who were diagnosed with genome sequencing after inconclusive exome sequencing tests.
Results show that in these cases, exome sequencing was limited by poor sensitivity for structural variants and non-coding variants, as well as biased coverage of coding regions. Authors note that these findings suggest that individuals presenting with neurodevelopmental disability could benefit from genome sequencing, either as a follow-up or in place of non-diagnostic exome sequencing.
Thorpe E, Williams T, Shaw C, Chekalin E, Ortega J, Robinson K, Button J, Jones MC, Campo MD, Basel D, McCarrier J, Keppen LD, Royer E, Foster-Bonds R, Duenas-Roque MM, Urraca N, Bosfield K, Brown CW, Lydigsen H, Mroczkowski HJ, Ward J, Sirchia F, Giorgio E, Vaux K, Salguero HP, Lumaka A, Mubungu G, Makay P, Ngole M, Lukusa PT, Vanderver A, Muirhead K, Sherbini O, Lah MD, Anderson K, Bazalar-Montoya J, Rodriguez RS, Cornejo-Olivas M, Milla-Neyra K, Shinawi M, Magoulas P, Henry D, Gibson K, Wiafe S, Jayakar P, Salyakina D, Masser-Frye D, Serize A, Perez JE, Taylor A, Shenbagam S, Abou Tayoun A, Malhotra A, Bennett M, Rajan V, Avecilla J, Warren A, Arseneault M, Kalista T, Crawford A, Ajay SS, Perry DL, Belmont J, Taft RJ. The impact of clinical genome sequencing in a global population with suspected rare genetic disease. Am J Hum Genet. 2024 Jul 11;111(7):1271-1281. doi: 10.1016/j.ajhg.2024.05.006. Epub 2024 Jun 5.
Gavazzi F, Vaia Y, Woidill S, Formanowski B, Peixoto de Barcelos I, Sevagamoorthy A, Modesti NB, Charlton L, Cusack SV, Vincent A, D'Aiello R, Jawad A, Galli J, Varesio C, Fazzi E, Orcesi S, Glanzman AM, Lorch S, DeMauro SB, Guez-Barber D, Waldman AT, Vanderver A, Adang LA. Nonverbal Cognitive Skills in Children With Aicardi Goutières Syndrome. Neurology. 2024 Jul 9;103(1):e209541. doi: 10.1212/WNL.0000000000209541. Epub 2024 Jun 10.
Kissell J, Rochmann C, Minini P, Eichler F, Stephen CD, Lau H, Toro C, Johnston JM, Krupnick R, Hamed A, Cox GF. Clinical outcome assessments of disease burden and progression in late-onset GM2 gangliosidoses. Mol Genet Metab. 2024 Jul;142(3):108512. doi: 10.1016/j.ymgme.2024.108512. Epub 2024 Jun 6.
Adang LA, Bonkowsky JL, Boelens JJ, Mallack E, Ahrens-Nicklas R, Bernat JA, Bley A, Burton B, Darling A, Eichler F, Eklund E, Emrick L, Escolar M, Fatemi A, Fraser JL, Gaviglio A, Keller S, Patterson MC, Orchard P, Orthmann-Murphy J, Santoro JD, Schöls L, Sevin C, Srivastava IN, Rajan D, Rubin JP, Van Haren K, Wasserstein M, Zerem A, Fumagalli F, Laugwitz L, Vanderver A. Consensus guidelines for the monitoring and management of metachromatic leukodystrophy in the United States. Cytotherapy. 2024 Jul;26(7):739-748. doi: 10.1016/j.jcyt.2024.03.487. Epub 2024 Apr 1.
Adang LA, Groeschel S, Grzyb C, D'Aiello R, Gavazzi F, Sherbini O, Bronner N, Patel A, Vincent A, Sevagamoorthy A, Mutua S, Muirhead K, Schmidt J, Pizzino A, Yu E, Jin D, Eichler F, Fraser JL, Emrick L, Van Haren K, Boulanger JM, Ruzhnikov M, Sylvain M, Nguyen CÉ, Potic A, Keller S, Fatemi A, Uebergang E, Poe M, Yazdani PA, Bernat J, Lindstrom K, Bonkowsky JL, Bernard G, Stutterd CA, Orchard P, Gupta AO, Ljungberg M, Groenborg S, Zambon A, Locatelli S, Fumagalli F, Elguen S, Kehrer C, Krägeloh-Mann I, Shults J, Vanderver A, Escolar ML. Developmental delay can precede neurologic regression in early onset metachromatic leukodystrophy. Mol Genet Metab. 2024 Aug;142(4):108521. doi: 10.1016/j.ymgme.2024.108521. Epub 2024 Jun 29. PMID: 38964050; PMCID: PMC11348664.
Metachromatic leukodystrophy (MLD) is an inherited lysosomal disorder caused by a missing or abnormal enzyme that cannot break down sulfatides (complex, fat-sugar molecules containing a sulfate group). Since therapies are most effective before patients begin experiencing symptoms, there is a critical need to define this window early in the disease course.
In this study, researchers explored the relationship between early development delay and neurologic regression in late-infantile MLD. The team studied medical records of 351 patients, including the specific ages of gain and loss of developmental milestones.
Results show that early developmental delay precedes regression in a subset of children affected by late-infantile MLD, defining an earlier onset of neurologic dysfunction than previously understood. As real-world data prior to diagnosis revealed early differences from typical development, authors note that close monitoring for early development delay in presymptomatic individuals may help with earlier diagnosis, leading to improved treatment decisions.
Adang LA, D'Aiello R, Takanohashi A, Woidill S, Gavazzi F, Behrens EM, Sullivan KE, Goldbach-Mansky R, de Jesus AA; AGS Clinical Trial Readiness Workgroup; Vanderver A, Shults J. IFN-signaling gene expression as a diagnostic biomarker for monogenic interferonopathies. JCI Insight. 2024 Jun 17;9(14):e178456. doi: 10.1172/jci.insight.178456.
Armangue T, Whitehead MT, Tonduti D, Farina L, Tavasoli AR, Vossough A, Bennett ML, Vaia Y, Bernard G, Salsano E, Mercimek-Andrews S, Waldman A, Vanderver A. Brainstem Chipmunk Sign: A Diagnostic Imaging Clue across All Subtypes of Alexander Disease. AJNR Am J Neuroradiol. 2024 Jun 7;45(6):769-772. doi: 10.3174/ajnr.A8220.
Posern C, Dreyer B, Maier SL, Eichler F, Gelb MH, Santer R, Bley A, Murko S. Quantification of N-acetyl-l-aspartate in dried blood spots: A simple and fast LC-MS/MS neonatal screening method for the diagnosis of Canavan disease. Mol Genet Metab. 2024 Jun;142(2):108489. doi: 10.1016/j.ymgme.2024.108489. Epub 2024 May 3.
Berger JA, Simpao AF, Dubow SR, McClung HA, Liu GW, Waldman AT, Drum ET. A retrospective observational cohort study of the anesthetic management and outcomes of pediatric patients with Alexander disease undergoing lumbar puncture or magnetic resonance imaging. Paediatr Anaesth. 2024 Aug;34(8):810-817. doi: 10.1111/pan.14937. Epub 2024 May 31. PMID: 38818870; PMCID: PMC11223980.
Alexander disease is a rare disorder of the nervous system characterized by leukodystrophy, or the destruction of myelin (the fatty coating surrounding nerve fibers). Patients with Alexander disease can experience developmental delay, seizures, difficulty swallowing, vomiting, and sleep apnea. These symptoms can also lead to complications under general anesthesia. However, not much is known about outcomes related to anesthesia for patients with Alexander disease.
In this study, researchers describe anesthetic outcomes of pediatric patients with Alexander disease undergoing magnetic resonance imaging or lumbar puncture. Among 40 patients undergoing 64 procedures, the team reviewed data on patient characteristics, anesthetic techniques, medications, and complications under anesthesia as well as in the following 24 hours.
Results show that participants did not experience significant complications while undergoing general anesthesia or monitored anesthesia care, demonstrating that patients with Alexander disease can safely be anesthetized for low-risk procedures. Authors note that further study is needed to understand the long-term safety outcomes of repeat anesthetic exposures in patients with Alexander disease.
Yska HAF, Turk BR, Fatemi A, Goodman J, Voermans M, Amos D, Amanat M, van de Stadt S, Engelen M, Smith-Fine A, Keller J. International validation of meaningfulness of postural sway and gait to assess myeloneuropathy in adults with adrenoleukodystrophy. J Inherit Metab Dis. 2024 May 25. doi: 10.1002/jimd.12753. Epub ahead of print. PMID: 38795020.
Adrenoleukodystrophy (ALD) is an X-linked disorder (on the X chromosome) characterized by the disruption in fat metabolism (break down) which leads to the accumulation of long-chain fatty acids throughout the nervous system, adrenal glands, and testes. Individuals with ALD experience a slowly progressive myeloneuropathy, which causes problems with balance and gait. Evaluating this progression can often be complicated due to the inconsistency of symptom patterns. However, wearable sensors could make it easier to collect more frequent information about balance and gait.
_x000D_ _x000D_In this study, researchers assessed balance and gait in adults with ALD using wearable sensors. The team measured postural body sway and gait in 120 participants using a type of wearable device called an accelerometer. Researchers also measured disease severity, as well as falling frequency and quality of life in men.
_x000D_ _x000D_Results show clinically meaningful relationships for sway and gait with use of an assistive device, falling frequency, and quality of life. Authors note that wearable accelerometers are a valid means to measure sway and gait in ALD, which could help improve clinical trial designs to assess myeloneuropathy and monitor disease progression.
Adang LA, Sevagamoorthy A, Sherbini O, Fraser JL, Bonkowsky JL, Gavazzi F, D'Aiello R, Modesti NB, Yu E, Mutua S, Kotes E, Shults J, Vincent A, Emrick LT, Keller S, Van Haren KP, Woidill S, Barcelos I, Pizzino A, Schmidt JL, Eichler F, Fatemi A, Vanderver A. Longitudinal natural history studies based on real-world data in rare diseases: Opportunity and a novel approach. Mol Genet Metab. 2024 May;142(1):108453. doi: 10.1016/j.ymgme.2024.108453. Epub 2024 Mar 18. PMID: 38522179.
In rare diseases, natural history studies are essential to understanding disease progression over time. Prospective studies are limited by fewer available patients at a given time, impacting the timely collection of natural history data. These studies are also unlikely to capture pre-diagnostic clinical trajectories in conditions where diagnostic delays are common.
_x000D_ _x000D_In this study, researchers shared a new approach to creating real-world data-based longitudinal natural history studies for rare diseases. The team outlined various strategies developed by the Global Leukodystrophy Initiative Clinical Trials Network. Strategies include use of standard operating procedures and rigorous processes for staff training, data extraction, source documentation, and data management.
_x000D_ _x000D_Authors note that these strategies will complement prospective studies by enabling the use of existing medical records to collect natural history data on large numbers of patients in a short time and map complete disease trajectory, including the time period before diagnosis.
de Barcelos IP, Woidill S, Gavazzi F, Modesti NB, Sevagamoorthy A, Vanderver A, Adang L. Systematic analysis of genotype-phenotype variability in siblings with Aicardi Goutières Syndrome (AGS). Mol Genet Metab. 2024 May;142(1):108346. doi: 10.1016/j.ymgme.2024.108346. Epub 2024 Feb 13.
Kiefer M, Simione M, Eichler FS, Townsend EL4. Development of an Infantile GM2 Clinical Rating Scale: Remote Assessment of Clinically Meaningful Health-Related Function. J Child Neurol. 2024 May;39(5-6):161-170. doi: 10.1177/08830738241246703. Epub 2024 Apr 25.
Fortin O, Christoffel K, Shoaib A, Venkatesan C, Cilli K, Schroeder JW, Alves C, Ganetzky RD, Fraser JL. Characteristic Fetal Brain MRI Abnormalities in Pyruvate Dehydrogenase Complex Deficiency. medRxiv. 2024 Apr 10:2024.04.08.24303574. doi: 10.1101/2024.04.08.24303574.
Chen Y, Dawes R, Kim HC, Stenton SL, Walker S, Ljungdahl A, Lord J, Ganesh VS, Ma J, Martin-Geary AC, Lemire G, D'Souza EN, Dong S, Ellingford JM, Adams DR, Allan K, Bakshi M, Baldwin EE, Berger SI, Bernstein JA, Brown NJ, Burrage LC, Chapman K, Compton AG, Cunningham CA, D'Souza P, Délot EC, Dias KR, Elias ER, Evans CA, Ewans L, Ezell K, Fraser JL, Gallacher L, Genetti CA, Grant CL, Haack T, Kuechler A, Lalani SR, Leitão E, Fevre AL, Leventer RJ, Liebelt JE, Lockhart PJ, Ma AS, Macnamara EF, Maurer TM, Mendez HR, Montgomery SB, Nassogne MC, Neumann S, O'Leary M, Palmer EE, Phillips J, Pitsava G, Pysar R, Rehm HL, Reuter CM, Revencu N, Riess A, Rius R, Rodan L, Roscioli T, Rosenfeld JA, Sachdev R, Simons C, Sisodiya SM, Snell P, Clair L, Stark Z, Tan TY, Tan NB, Temple SE, Thorburn DR, Tifft CJ, Uebergang E, VanNoy GE, Vilain E, Viskochil DH, Wedd L, Wheeler MT, White SM, Wojcik M, Wolfe LA, Wolfenson Z, Xiao C, Zocche D, Rubenstein JL, Markenscoff-Papadimitriou E, Fica SM, Baralle D, Depienne C, MacArthur DG, Howson JM, Sanders SJ, O'Donnell-Luria A, Whiffin N. De novo variants in the non-coding spliceosomal snRNA gene RNU4-2 are a frequent cause of syndromic neurodevelopmental disorders. medRxiv. 2024 Apr 9:2024.04.07.24305438. doi: 10.1101/2024.04.07.24305438.
Gold JI, Stefanatos AK, Fraser JL, Vanderver A, Cuddapah S. Enasidenib-induced hepatitis in an individual with Type II D2-hydroxyglutaric aciduria. JIMD Rep. 2024 Apr 16;65(3):156-162. doi: 10.1002/jmd2.12421. eCollection 2024 May.
Ashton NJ, Di Molfetta G, Tan K, Blennow K, Zetterberg H, Messing A. Plasma concentrations of glial fibrillary acidic protein, neurofilament light, and tau in Alexander disease. Neurol Sci. 2024 Apr 1. doi: 10.1007/s10072-024-07495-8. Epub ahead of print. PMID: 38558318.
Alexander disease is a rare disorder of the nervous system characterized by leukodystrophy, or the destruction of myelin (the fatty coating surrounding nerve fibers). Biomarkers are needed to help researchers monitor the progression of the disease and response to treatments. Elevated levels of the GFAP protein in the blood of patients with Alexander disease could serve as a possible biomarker. However, therapies currently in development involve targeting GFAP for treatment, highlighting a critical need for additional biomarkers.
_x000D_ _x000D_In this study, researchers explored the potential of biomarkers used in other neurodegenerative diseases for Alexander disease. The team measured concentrations of GFAP, neurofilament light, and tau in blood samples from individuals with Alexander disease and healthy controls.
_x000D_ _x000D_Results show significant changes in these levels in individuals with Alexander disease, especially those with infantile onset.
Cusack SV, Gavazzi F, de Barcelos IP, Modesti NB, Woidill S, Formanowski B, DeMauro SB, Lorch S, Vincent A, Jawad AF, Estilow T, Glanzman AM, Vanderver A, Adang LA. Characterization of Fine Motor and Visual Motor Skills in Aicardi-Goutières Syndrome. J Child Neurol. 2024 Mar;39(3-4):147-154. doi: 10.1177/08830738241241786. Epub 2024 Mar 27.
Gavazzi F, Gonzalez CD, Arnold K, Swantkowski M, Charlton L, Modesti N, Dar AA, Vanderver A, Bennett M, Adang LA. Nucleotide metabolism, leukodystrophies, and CNS pathology. J Inherit Metab Dis. 2024 Feb 29:10.1002/jimd.12721. doi: 10.1002/jimd.12721. Online ahead of print.
Nagy A, Molay F, Hargadon S, Brito Pires C, Grant N, De La Rosa Abreu L, Chen JY, D'Souza P, Macnamara E, Tifft C, Becker C, Melo De Gusmao C, Khurana V, Neumeyer AM, Eichler FS. The spectrum of neurological presentation in individuals affected by TBL1XR1 gene defects. Orphanet J Rare Dis. 2024 Feb 20;19(1):79. doi: 10.1186/s13023-024-03083-3. PMID: 38378692; PMCID: PMC10880200.
TBL1XR1-related disorder is a group of neurodevelopmental disorders caused by variants in the TBL1XR1 gene. As these disorders are rare with a wide range of characteristics, not much is known about the developmental trajectory and progression of neurological symptoms over time.
_x000D_ _x000D_In this study, researchers describe the largest group of patients to date with TBL1XR1-related disorder. The team surveyed caregivers of 41 patients with TBL1XR1-related disorder, focusing on the pregnancy and perinatal course, caregiver-reported developmental trajectory, associated symptoms and diagnoses, neurological progression over time, and genetic information.
_x000D_ _x000D_Results reflect the spectrum of diverse traits in TBL1XR1-related disorder, including developmental delay and regression ranging in severity. Seizures were common, which could be related to language regression. Authors note that further study is needed to determine whether functional differences caused by different variants in the TBL1XR1 gene explain the range of characteristics in this disorder.
Ahmed F, Do N, Vanderver AL, Treat JR. Dyschromatosis symmetrica hereditaria: A clue to early diagnosis of Aicardi-Goutières syndrome. Pediatr Dermatol. 2024 Jan-Feb;41(1):156-157. doi: 10.1111/pde.15437. Epub 2023 Sep 28.
Goldberg G, Coelho L, Mo G, Adang LA, Patne M, Chen Z, Garcia-Bassets I, Mesci P, Muotri AR. TREX1 is required for microglial cholesterol homeostasis and oligodendrocyte terminal differentiation in human neural assembloids. Mol Psychiatry. 2023 Dec 21. doi: 10.1038/s41380-023-02348-w. Online ahead of print.
Gong Y, Laheji F, Berenson A, Li Y, Moser A, Qian A, Frosch M, Sadjadi R, Hahn R, Maguire CA, Eichler F. Role of Basal Forebrain Neurons in Adrenomyeloneuropathy in Mice and Humans. Ann Neurol. 2023 Dec 7. doi: 10.1002/ana.26849. Online ahead of print.
Joung J, Gallison K, Sollee JJ, Vigilante N, Cooper H, Liu GW, Ballester L, Faig W, Waldman AT. Acquisition and Loss of Developmental Milestones and Time to Disease-Related Outcomes in Cerebral Alexander Disease. J Child Neurol. 2023 Dec;38(13-14):672-678. doi: 10.1177/08830738231210040. Epub 2023 Nov 3.
Adang LA, Mowafy S, Herbst ZM, Zhou Z, Schlotawa L, Radhakrishnan K, Bentley B, Pham V, Yu E, Pillai NR, Orchard PJ, De Castro M, Vanderver A, Pasquali M, Gelb MH, Ahrens-Nicklas RC. Biochemical signatures of disease severity in multiple sulfatase deficiency. J Inherit Metab Dis. 2023 Oct 23. doi: 10.1002/jimd.12688. Online ahead of print.
Ramirez Alcantara J, Grant NR, Sethuram S, Nagy A, Becker C, Sahai I, Stanley T, Halper A, Eichler FS. Early Detection of Adrenal Insufficiency: The Impact of Newborn Screening for Adrenoleukodystrophy. J Clin Endocrinol Metab. 2023 Oct 18;108(11):e1306-e1315.
Adrenoleukodystrophy (ALD) is an X-linked disorder (on the X chromosome) characterized by accumulation of very long-chain fatty acids throughout the nervous system, adrenal glands, and testes. Males with ALD have a high risk of developing adrenal insufficiency, which can be life-threatening when undetected. Although newborn screening for ALD is becoming more common, its impact on clinical management has not yet been reported.
In this study, researchers investigated the impact of newborn screening on time to diagnosis of adrenal insufficiency in children with ALD. The team conducted a medical chart review of 116 patients with ALD, extracting information about diagnosis in all patients and adrenal insufficiency surveillance, diagnosis, and treatment in boys with ALD.
Results suggest that implementing newborn screening for ALD leads to significantly earlier detection of adrenal insufficiency, as well as earlier initiation of glucocorticoid supplementation in boys affected by ALD.
Weinhofer I, Rommer P, Gleiss A, Ponleitner M, Zierfuss B, Waidhofer-Söllner P, Fourcade S, Grabmeier-Pfistershammer K, Reinert MC, Göpfert J, Heine A, Yska HAF, Casasnovas C, Cantarín V, Bergner CG, Mallack E, Forss-Petter S, Aubourg P, Bley A, Engelen M, Eichler F, Lund TC, Pujol A, Köhler W, Kühl JS, Berger J. Biomarker-based risk prediction for the onset of neuroinflammation in X-linked adrenoleukodystrophy. EBioMedicine. 2023 Oct;96:104781. doi: 10.1016/j.ebiom.2023.104781. Epub 2023 Sep 7.
Mirchi A, Guay SP, Tran LT, Wolf NI, Vanderver A, Brais B, Sylvain M, Pohl D, Rossignol E, Saito M, Moutton S, González-Gutiérrez-Solana L, Thiffault I, Kruer MC, Moron DG, Kauffman M, Goizet C, Sztriha L, Glamuzina E, Melançon SB, Naidu S, Retrouvey JM, Lacombe S, Bernardino-Cuesta B, De Bie I, Bernard G. Craniofacial features of POLR3-related leukodystrophy caused by biallelic variants in POLR3A, POLR3B and POLR1C. J Med Genet. 2023 Oct;60(10):1026-1034. doi: 10.1136/jmg-2023-109223. Epub 2023 May 16. PMID: 37197783
RNA polymerase III-related or 4H leukodystrophy (POLR3-HLD) is a rare genetic disorder characterized by hypomyelination (inability to produce sufficient myelin, the fatty coating surrounding nerve fibers, at normal levels during development), neurological dysfunction, hypodontia (missing teeth), and hypogonadotropic hypogonadism (delayed puberty). Description of craniofacial features in individuals with POLR3-HLD is currently very limited.
In this study, researchers assessed the craniofacial features of 31 patients with POLR3-HLD. The team also proposed genotype-phenotype correlations based on patients’ facial features.
Results demonstrate that craniofacial abnormalities are common in patients with POLR3-HLD. Authors note that these findings will assist clinicians in diagnosing POLR3-HLD, help to provide care directed to this patient population’s specific needs, and allow future studies characterizing the underlying pathophysiology.
Wong KN, Botto LD, He M, Baker PR 2nd, Vanderver AL, Bonkowsky JL. Novel SLC13A3 Variants and Cases of Acute Reversible Leukoencephalopathy and α-Ketoglutarate Accumulation and Literature Review. Neurol Genet. 2023 Sep 26;9(6):e200101. doi: 10.1212/NXG.0000000000200101. eCollection 2023 Dec.
Schoenmakers DH, Leferink PS, Vanderver A, Bonkowsky JL, Krägeloh-Mann I, Bernard G, Bertini E, Fatemi A, Fogel BL, Wolf NI, Skwirut D, Buck A, Holberg B, Saunier-Vivar EF, Rauner R, Dekker H, van Bokhoven P, Stellingwerff MD, Berkhof J, van der Knaap MS. Core protocol development for phase 2/3 clinical trials in the leukodystrophy vanishing white matter: a consensus statement by the VWM consortium and patient advocates. BMC Neurol. 2023 Aug 17;23(1):305. doi: 10.1186/s12883-023-03354-9.
Gavazzi F, Patel V, Charsar B, Glanzman A, Erler J, Sevagamoorthy A, McKenzie E, Kornafel T, Ballance E, Pierce SR, Teng M, Formanowski B, Woidill S, Shults J, Wassmer E, Tonduti D, Magrinelli F, Bernard G, Van Der Knaap M, Wolf N, Adang L, Vanderver A. Gross Motor Function in Pediatric Onset TUBB4A-Related Leukodystrophy: GMFM-88 Performance and Validation of GMFC-MLD in TUBB4A. J Child Neurol. 2023 Aug;38(8-9):498-504. doi: 10.1177/08830738231188159. Epub 2023 Jul 17.
Gavazzi F, Glanzman AM, Woidill S, Formanowski B, Dixit A, Isaacs D, Kornafel T, Ballance E, Pierce SR, Modesti N, Barcelos I, Cusack SV, Jan AK, Flores Z, Sherbini O, Vincent A, D'Aiello R, Lorch SA, DeMauro SB, Jawad A, Vanderver A, Adang L. Exploration of Gross Motor Function in Aicardi-Goutières Syndrome. J Child Neurol. 2023 Jul 27:8830738231188753. doi: 10.1177/08830738231188753. Epub ahead of print. PMID: 37499181
Aicardi-Goutières syndrome (AGS) is a rare genetic disorder characterized by a spectrum of motor abilities. The AGS Severity Scale is used to measure outcomes in individuals with AGS. However, because of the relatively limited granularity of this tool, there is a need to define tools that can measure function across the AGS spectrum.
In this study, researchers explored gross motor function as an outcome measure of AGS. The team administered the Gross Motor Function Measure–88 (GMFM-88) and AGS Severity Scale in 71 individuals affected by AGS, characterizing performance variability by genotype.
Results support the GMFM-88 as a potential clinical outcome assessment in subsets of the AGS population. Authors note the need for additional validation of outcome measures that can reflect the diverse gross motor function observed in individuals with AGS, including low motor function.
Al-Saady M, Beerepoot S, Plug BC, Breur M, Galabova H, Pouwels PJW, Boelens JJ, Lindemans C, van Hasselt PM, Matzner U, Vanderver A, Bugiani M, van der Knaap MS, Wolf NI. Neurodegenerative disease after hematopoietic stem cell transplantation in metachromatic leukodystrophy. Ann Clin Transl Neurol. 2023 Jul;10(7):1146-1159. doi: 10.1002/acn3.51796. Epub 2023 May 22.
Köhler W, Engelen M, Eichler F, Lachmann R, Fatemi A, Sampson J, Salsano E, Gamez J, Molnar MJ, Pascual S, Rovira M, Vilà A, Pina G, Martín-Ugarte I, Mantilla A, Pizcueta P, Rodríguez-Pascau L, Traver E, Vilalta A, Pascual M, Martinell M, Meya U, Mochel F; ADVANCE Study Group. Safety and efficacy of leriglitazone for preventing disease progression in men with adrenomyeloneuropathy (ADVANCE): a randomised, double-blind, multi-centre, placebo-controlled phase 2-3 trial. Lancet Neurol. 2023 Feb;22(2):127-136. doi: 10.1016/S1474-4422(22)00495-1.
Srivastava S, Shaked HM, Gable K, Gupta SD, Pan X, Somashekarappa N, Han G, Mohassel P, Gotkine M, Doney E, Goldenberg P, Tan QKG, Gong Y, Kleinstiver B, Wishart B, Cope H, Pires CB, Stutzman H, Spillmann RC; Undiagnosed Disease Network; Sadjadi R, Elpeleg O, Lee CH, Bellen HJ, Edvardson S, Eichler F, Dunn TM. SPTSSA variants alter sphingolipid synthesis and cause a complex hereditary spastic paraplegia. Brain. 2023 Jan 30:awac460. doi: 10.1093/brain/awac460. Epub ahead of print. PMID: 36718090.
Hereditary spastic paraplegia (HSP) is a group of neurodegenerative disorders that primarily affect the upper motor neurons. In the nervous system, a diverse family of lipids called sphingolipids play a critical role in structural and signaling functions. The synthesis of sphingolipids is regulated by the protein SPTSSA.
In this study, researchers identified three children with a complex form of HSP. The team used exome sequencing to discover two different disease-causing variants in the SPTSSA gene. Next, they investigated the effects of these variants on sphingolipid synthesis.
Findings showed that the variants in SPTSSA caused excessive sphingolipid synthesis, leading to HSP. Authors note that these findings provide a better understanding of the elevated sphingolipid synthesis involved in progressive neurodegenerative diseases.
Modesti NB, Evans SH, Jaffe N, Vanderver A, Gavazzi F. Early recognition of patients with leukodystrophies. Curr Probl Pediatr Adolesc Health Care. 2022 Dec;52(12):101311. doi: 10.1016/j.cppeds.2022.101311. Epub 2022 Dec 2.
Perez G, Young L, Kravitz R, Sheehan D, Adang L, Van Haren K, Lin JL, Jaffe NN, Kuo D, Ball L, Keller J, Sank J, DiVito D, Naime S. Pulmonological issues. Curr Probl Pediatr Adolesc Health Care. 2022 Dec;52(12):101313. doi: 10.1016/j.cppeds.2022.101313. Epub 2022 Dec 5.
Engelen M, van Ballegoij WJC, Mallack EJ, Van Haren KP, Köhler W, Salsano E, van Trotsenburg ASP, Mochel F, Sevin C, Regelmann MO, Tritos NA, Halper A, Lachmann RH, Davison J, Raymond GV, Lund TC, Orchard PJ, Kuehl JS, Lindemans CA, Caruso P, Turk BR, Moser AB, Vaz FM, Ferdinandusse S, Kemp S, Fatemi A, Eichler FS, Huffnagel IC. International Recommendations for the Diagnosis and Management of Patients With Adrenoleukodystrophy: A Consensus-Based Approach. Neurology. 2022 Nov 22;99(21):940-951. doi: 10.1212/WNL.0000000000201374. Epub 2022 Sep 29.
Harting I, Garbade SF, Rosendaal SD, Mohr A, Sherbini O, Vanderver A, Wolf NI. Identification of PMD subgroups using a myelination score for PMD. Eur J Paediatr Neurol. 2022 Nov;41:71-79. doi: 10.1016/j.ejpn.2022.10.003. Epub 2022 Nov 4.
Eichler F, Sevin C, Barth M, Pang F, Howie K, Walz M, Wilds A, Calcagni C, Chanson C, Campbell L. Understanding caregiver descriptions of initial signs and symptoms to improve diagnosis of metachromatic leukodystrophy. Orphanet J Rare Dis. 2022 Oct 4;17(1):370. doi: 10.1186/s13023-022-02518-z.
Gavazzi F, Pierce SR, Vithayathil J, Cunningham K, Anderson K, McCann J, Moll A, Muirhead K, Sherbini O, Prange E, Dubbs H, Tochen L, Fraser J, Helbig I, Lewin N, Thakur N, Adang LA. Psychometric outcome measures in beta-propeller protein-associated neurodegeneration (BPAN). Mol Genet Metab. 2022 Sep-Oct;137(1-2):26-32. doi: 10.1016/j.ymgme.2022.07.009. Epub 2022 Jul 20.
Helman G, Takanohashi A, Hagemann TL, Perng MD, Walkiewicz M, Woidill S, Sase S, Cross Z, Du Y, Zhao L, Waldman A, Haake BC, Fatemi A, Brenner M, Sherbini O, Messing A, Vanderver A, Simons C. Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform. Hum Mutat. 2022 Sep;43(9):1344. doi: 10.1002/humu.24400.
Stutterd CA, Vanderver A, Lockhart PJ, Helman G, Pope K, Uebergang E, Love C, Delatycki MB, Thorburn D, Mackay MT, Peters H, Kornberg AJ, Patel C, Rodriguez-Casero V, Waak M, Silberstein J, Sinclair A, Nolan M, Field M, Davis MR, Fahey M, Scheffer IE, Freeman JL, Wolf NI, Taft RJ, van der Knaap MS, Simons C, Leventer RJ. Unclassified white matter disorders: A diagnostic journey requiring close collaboration between clinical and laboratory services. Eur J Med Genet. 2022 Sep;65(9):104551. doi: 10.1016/j.ejmg.2022.104551. Epub 2022 Jul 5.
Adang L. Leukodystrophies. Continuum (Minneap Minn). 2022 Aug 1;28(4):1194-1216. doi: 10.1212/CON.0000000000001130.
Wongkittichote P, Magistrati M, Shimony JS, Smyser CD, Fatemi SA, Fine AS, Bellacchio E, Dallabona C, Shinawi M. Functional analysis of missense DARS2 variants in siblings with leukoencephalopathy with brain stem and spinal cord involvement and lactate elevation. Mol Genet Metab. 2022 Aug;136(4):260-267. doi: 10.1016/j.ymgme.2022.07.002. Epub 2022 Jul 5.
Alves CAPF, Sherbini O, D'Arco F, Steel D, Kurian MA, Radio FC, Ferrero GB, Carli D, Tartaglia M, Balci TB, Powell-Hamilton NN, Schrier Vergano SA, Reutter H, Hoefele J, Günthner R, Roeder ER, Littlejohn RO, Lessel D, Lüttgen S, Kentros C, Anyane-Yeboa K, Catarino CB, Mercimek-Andrews S, Denecke J, Lyons MJ, Klopstock T, Bhoj EJ, Bryant L, Vanderver A. Brain Abnormalities in Patients with Germline Variants in H3F3: Novel Imaging Findings and Neurologic Symptoms Beyond Somatic Variants and Brain Tumors. AJNR Am J Neuroradiol. 2022 Jul;43(7):1048-1053. doi: 10.3174/ajnr.A7555. Epub 2022 Jun 30.
Adang LA, Gavazzi F, D'Aiello R, Isaacs D, Bronner N, Arici ZS, Flores Z, Jan A, Scher C, Sherbini O, Behrens EM, Goldbach-Mansky R, Olson TS, Lambert MP, Sullivan KE, Teachey DT, Witmer C, Vanderver A, Shults J. Hematologic abnormalities in Aicardi Goutières Syndrome. Mol Genet Metab.. 2022 Jun 16:S1096-7192(22)00339-0. doi: 10.1016/j.ymgme.2022.06.003. Epub ahead of print. PMID: 35786528.
Aicardi Goutières syndrome (AGS) is an inherited disease that is associated with early onset neurologic disability and systemic inflammation. Cytopenias—conditions in which there are lower-than-normal numbers of blood cells—are a potentially serious, but poorly understood, complication of AGS. As new treatment options are developed, it is important to understand the roles of the disease versus the treatment in hematologic abnormalities, allowing for better management of cytopenia. In this study, researchers identified novel patterns of hematologic abnormalities in AGS. The team collected laboratory data throughout the lifespan from 142 individuals with AGS. Results showed that AGS results in multilineage cytopenias not limited to the neonatal period. Neutropenia, anemia, and thrombocytopenia were common. For patients on the treatment baricitinib, moderate to severe graded events of neutropenia, anemia, and leukopenia were more common, but rarely of clinical consequence. Based on these results, authors recommend careful monitoring of hematologic parameters in children with AGS throughout the lifespan, especially while on therapy. Authors also note that AGS should be considered in children with neurologic impairment of unclear cause and hematologic abnormalities.
Mallack EJ, Van Haren KP, Torrey A, van de Stadt S, Engelen M, Raymond GV, Fatemi A, Eichler FS. Presymptomatic Lesion in Childhood Cerebral Adrenoleukodystrophy: Timing and Treatment. Neurology. 2022 May 24:10.1212/WNL.0000000000200571. doi: 10.1212/WNL.0000000000200571. Online ahead of print.
Cetin Gedik K, Lamot L, Romano M, Demirkaya E, Piskin D, Torreggiani S, Adang LA, Armangue T, Barchus K, Cordova DR, Crow YJ, Dale RC, Durrant KL, Eleftheriou D, Fazzi EM, Gattorno M, Gavazzi F, Hanson EP, Lee-Kirsch MA, Montealegre Sanchez GA, Neven B, Orcesi S, Ozen S, Poli MC, Schumacher E, Tonduti D, Uss K, Aletaha D, Feldman BM, Vanderver A, Brogan PA, Goldbach-Mansky R. The 2021 European Alliance of Associations for Rheumatology/American College of Rheumatology points to consider for diagnosis and management of autoinflammatory type I interferonopathies: CANDLE/PRAAS, SAVI and AGS. Ann Rheum Dis. 2022 May;81(5):601-613. doi: 10.1136/annrheumdis-2021-221814. Epub 2022 Jan 27.
Casas-Alba D, Darling A, Caballero E, Mensa-Vilaró A, Bartrons J, Antón J, García-Cazorla À, Vanderver A, Armangué T. Efficacy of baricitinib on chronic pericardial effusion in a patient with Aicardi-Goutières syndrome. Rheumatology (Oxford). 2022 Apr 11;61(4):e87-e89. doi: 10.1093/rheumatology/keab860.
Stellingwerff MD, Nulton C, Helman G, Roosendaal SD, Benko WS, Pizzino A, Bugiani M, Vanderver A, Simons C, van der Knaap MS. Early-Onset Vascular Leukoencephalopathy Caused by Bi-Allelic NOTCH3 Variants. Neuropediatrics. 2022 Apr;53(2):115-121. doi: 10.1055/a-1739-2722. Epub 2022 Jan 13. PMID: 35026854.
Macintosh J, Derksen A, Poulin C, Braverman N, Vanderver A, Thiffault I, Albrecht S, Bernard G. Novel biallelic variants in NRROS associated with a lethal microgliopathy, brain calcifications, and neurodegeneration. Neurogenetics. 2022 Apr;23(2):151-156. doi: 10.1007/s10048-022-00683-8. Epub 2022 Jan 31. PMID: 35099671.
Bonkowsky JL, Wilkes J. Time to Transplant in X-Linked Adrenoleukodystrophy. J Child Neurol.. 2022 Apr;37(5):397-400. doi: 10.1177/08830738221081141. Epub 2022 Mar 3.
Smith Fine A, Kaufman M, Goodman J, Turk B, Bastian A, Lin D, Fatemi A, Keller J. Wearable sensors detect impaired gait and coordination in LBSL during remote assessments. Ann Clin Transl Neurol. 2022 Apr;9(4):468-477. doi: 10.1002/acn3.51509. Epub 2022 Mar 8.
Winkelman JW, Grant NR, Molay F, Stephen CD, Sadjadi R, Eichler FS. Restless Legs Syndrome in X-linked adrenoleukodystrophy. Sleep Med. 2022 Mar;91:31-34. doi: 10.1016/j.sleep.2022.02.008. Epub 2022 Feb 16. PMID: 35245789; PMCID: PMC9035065.
Keller JL, Eloyan A, Raymond GV, Fatemi A, Zackowski KM. Sensorimotor outcomes in adrenomyeloneuropathy show significant disease progression. J Inherit Metab Dis. 2022 Mar;45(2):308-317. doi: 10.1002/jimd.12457. Epub 2021 Dec 9. PMID: 34796974; PMCID: PMC8987487.
Papapetropoulos S, Pontius A, Finger E, Karrenbauer V, Lynch DS, Brennan M, Zappia S, Koehler W, Schoels L, Hayer SN, Konno T, Ikeuchi T, Lund T, Orthmann-Murphy J, Eichler F, Wszolek ZK. Adult-Onset Leukoencephalopathy With Axonal Spheroids and Pigmented Glia: Review of Clinical Manifestations as Foundations for Therapeutic Development. Front Neurol. 2022 Feb 3;12:788168. doi: 10.3389/fneur.2021.788168. eCollection 2021.
van der Knaap MS, Bonkowsky JL, Vanderver A, Schiffmann R, Krägeloh-Mann I, Bertini E, Bernard G, Fatemi SA, Wolf NI, Saunier-Vivar E, Rauner R, Dekker H, van Bokhoven P, van de Ven P, Leferink PS. Therapy Trial Design in Vanishing White Matter: An Expert Consortium Opinion. Neurol Genet. 2022 Feb 2;8(2):e657. doi: 10.1212/NXG.0000000000000657. eCollection 2022 Apr.
Gavazzi F, Fraser JL, Bloom M, Tochen L, Rhee J, Kwan M, Victoria T, Teachey DT, Ho CY, Vanderver A, Linn RL. Hodgkin lymphoma in an individual with TREX1-mediated Aicardi Goutières syndrome. Pediatr Blood Cancer. 2022 Jan;69(1):e29322. doi: 10.1002/pbc.29322. Epub 2021 Sep 7.
Ghabash G, Wilkes J, Barney BJ, Bonkowsky JL. Hospitalization Burden and Incidence of Krabbe Disease. J Child Neurol. 2022 Jan;37(1):12-19. doi: 10.1177/08830738211027717. Epub 2021 Oct 20.
Muirhead KJ, Clause AR, Schlachetzki Z, Dubbs H, Perry DL, Hagelstrom RT, Taft RJ, Vanderver A. Genome sequencing identifies three molecular diagnoses including a mosaic variant in the COL2A1 gene in an individual with Pol III-related leukodystrophy and Feingold syndrome. Cold Spring Harb Mol Case Stud. 2021 Dec 9;7(6):a006143. doi: 10.1101/mcs.a006143. Print 2021 Dec.
Waldman AT, Benson L, Sollee JR, Lavery AM, Liu GW, Green AJ, Waubant E, Heidary G, Conger D, Graves J, Greenberg B. Interocular Difference in Retinal Nerve Fiber Layer Thickness Predicts Optic Neuritis in Pediatric-Onset Multiple Sclerosis. J Neuroophthalmol. 2021 Dec 1;41(4):469-475. doi: 10.1097/WNO.0000000000001070.
Gavazzi F, Cross ZM, Woidill S, McMann JM, Rand EB, Takanohashi A, Ulrick N, Shults J, Vanderver AL, Adang L. Hepatic Involvement in Aicardi-Goutières Syndrome. Neuropediatrics. 2021 Dec;52(6):441-447. doi: 10.1055/s-0040-1722673. Epub 2021 Jan 14.
Gavazzi F, Adang L, Waldman A, Jan AK, Liu G, Lorch SA, DeMauro SB, Shults J, Pierce SR, Ballance E, Kornafel T, Harrington A, Glanzman AM, Vanderver A. Reliability of the Telemedicine Application of the Gross Motor Function Measure-88 in Patients With Leukodystrophy. Pediatr Neurol. 2021 Dec;125:34-39. doi: 10.1016/j.pediatrneurol.2021.09.012. Epub 2021 Sep 24. PMID: 34624609; PMCID: PMC8629609.
Ghabash G, Wilkes J, Bonkowsky JL. National U.S. Patient and Transplant Data for Krabbe Disease. Front Pediatr. 2021 Nov 11;9:764626. doi: 10.3389/fped.2021.764626. eCollection 2021.
Mallack EJ, Askin G, van de Stadt S, Caruso PA, Musolino PL, Engelen M, Niogi SN, Eichler FS. A Longitudinal Analysis of Early Lesion Growth in Presymptomatic Patients with Cerebral Adrenoleukodystrophy. AJNR Am J Neuroradiol. 2021 Oct;42(10):1904-1911. doi: 10.3174/ajnr.A7250. Epub 2021 Sep 9.
Malhotra A, Ziegler A, Shu L, Perrier R, Amlie-Wolf L, Wohler E, Lygia de Macena Sobreira N, Colin E, Vanderver A, Sherbini O, Stouffs K, Scalais E, Serretti A, Barth M, Navet B, Rollier P, Xi H, Wang H, Zhang H, Perry DL, Ferrarini A, Colombo R, Pepler A, Schneider A, Tomiwa K, Okamoto N, Matsumoto N, Miyake N, Taft R, Mao X, Bonneau D. De novo missense variants in LMBRD2 are associated with developmental and motor delays, brain structure abnormalities and dysmorphic features. J Med Genet. 2021 Oct;58(10):712-716. doi: 10.1136/jmedgenet-2020-107137. Epub 2020 Aug 20.
Barczykowski AL, Langan TJ, Vanderver A, Jalal K, Carter RL. Death rates in the U.S. due to Leukodystrophies with pediatric forms. Am J Med Genet A. 2021 Aug;185(8):2361-2373. doi: 10.1002/ajmg.a.62248. Epub 2021 May 7.
Helman G, Zerem A, Almad A, Hacker JL, Woidill S, Sase S, LeFevre AN, Ekstein J, Johansson MM, Stutterd CA, Taft RJ, Simons C, Grinspan JB, Pizzino A, Schmidt JL, Harding B, Hirsch Y, Viaene AN, Fattal-Valevski A, Vanderver A. Further Delineation of the Clinical and Pathologic Features of HIKESHI-Related Hypomyelinating Leukodystrophy. Pediatr Neurol. 2021 Aug;121:11-19. doi: 10.1016/j.pediatrneurol.2021.04.014. Epub 2021 May 14.
Roosendaal SD, van de Brug T, Alves CAPF, Blaser S, Vanderver A, Wolf NI, van der Knaap MS. Imaging Patterns Characterizing Mitochondrial Leukodystrophies. AJNR Am J Neuroradiol. 2021 Jul;42(7):1334-1340. doi: 10.3174/ajnr.A7097. Epub 2021 Apr 1.
Bley A, Denecke J, Kohlschütter A, Schön G, Hischke S, Guder P, Bierhals T, Lau H, Hempel M, Eichler FS. The natural history of Canavan disease: 23 new cases and comparison with patients from literature. Orphanet J Rare Dis. 2021 May 19;16(1):227. doi: 10.1186/s13023-020-01659-3.
Mallack EJ, Turk BR, Yan H, Price C, Demetres M, Moser AB, Becker C, Hollandsworth K, Adang L, Vanderver A, Van Haren K, Ruzhnikov M, Kurtzberg J, Maegawa G, Orchard PJ, Lund TC, Raymond GV, Regelmann M, Orsini JJ, Seeger E, Kemp S, Eichler F, Fatemi A. MRI surveillance of boys with X-linked adrenoleukodystrophy identified by newborn screening: Meta-analysis and consensus guidelines. J Inherit Metab Dis. 2021 May;44(3):728-739. doi: 10.1002/jimd.12356. Epub 2021 Jan 9.
Gavazzi F, Charsar BA, Williams C, Shults J, Alves CA, Adang L, Vanderver A. Acquisition of Developmental Milestones in Hypomyelination With Atrophy of the Basal Ganglia and Cerebellum and Other TUBB4A-Related Leukoencephalopathy. J Child Neurol. 2021 Apr 12:883073821000977. doi: 10.1177/0883073821000977. Online ahead of print.
Weinhofer I, Rommer P, Zierfuss B, Altmann P, Foiani M, Heslegrave A, Zetterberg H, Gleiss A, Musolino PL, Gong Y, Forss-Petter S, Berger T, Eichler F, Aubourg P, Köhler W, Berger J. Neurofilament light chain as a potential biomarker for monitoring neurodegeneration in X-linked adrenoleukodystrophy. Nat Commun. 2021 Mar 22;12(1):1816. doi: 10.1038/s41467-021-22114-2.
Ramirez Alcantara J, Halper A. Adrenal insufficiency updates in children. Curr Opin Endocrinol Diabetes Obes. 2021 Feb 1;28(1):75-81. doi: 10.1097/MED.0000000000000591.
Piccoli C, Bronner N, Gavazzi F, Dubbs H, De Simone M, De Giorgis V, Orcesi S, Fazzi E, Galli J, Masnada S, Tonduti D, Varesio C, Vanderver A, Vossough A, Adang L. Late-Onset Aicardi-Goutières Syndrome: A Characterization of Presenting Clinical Features. Pediatr Neurol. 2021 Feb;115:1-6. doi: 10.1016/j.pediatrneurol.2020.10.012. Epub 2020 Nov 2.
Pelletier F, Perrier S, Cayami FK, Mirchi A, Saikali S, Tran LT, Ulrick N, Guerrero K, Rampakakis E, van Spaendonk RML, Naidu S, Pohl D, Gibson WT, Demos M, Goizet C, Tejera-Martin I, Potic A, Fogel BL, Brais B, Sylvain M, Sébire G, Lourenço CM, Bonkowsky JL, Catsman-Berrevoets C, Pinto PS, Tirupathi S, Strømme P, de Grauw T, Gieruszczak-Bialek D, Krägeloh-Mann I, Mierzewska H, Philippi H, Rankin J, Atik T, Banwell B, Benko WS, Blaschek A, Bley A, Boltshauser E, Bratkovic D, Brozova K, Cimas I, Clough C, Corenblum B, Dinopoulos A, Dolan G, Faletra F, Fernandez R, Fletcher J, Garcia Garcia ME, Gasparini P, Gburek-Augustat J, Gonzalez Moron D, Hamati A, Harting I, Hertzberg C, Hill A, Hobson GM, Innes AM, Kauffman M, Kirwin SM, Kluger G, Kolditz P, Kotzaeridou U, La Piana R, Liston E, McClintock W, McEntagart M, McKenzie F, Melançon S, Misbahuddin A, Suri M, Monton FI, Moutton S, Murphy RPJ, Nickel M, Onay H, Orcesi S, Özkınay F, Patzer S, Pedro H, Pekic S, Pineda Marfa M, Pizzino A, Plecko B, Poll-The BT, Popovic V, Rating D, Rioux MF, Rodriguez Espinosa N, Ronan A, Ostergaard JR, Rossignol E, Sanchez-Carpintero R, Schossig A, Senbil N, Sønderberg Roos LK, Stevens CA, Synofzik M, Sztriha L, et al. Endocrine and Growth Abnormalities in 4H Leukodystrophy Caused by Variants in POLR3A, POLR3B, and POLR1C. J Clin Endocrinol Metab. 2021 Jan 23;106(2):e660-e674. doi: 10.1210/clinem/dgaa700.
Engelen M, Kemp S, Eichler F. Endocrine dysfunction in adrenoleukodystrophy. Handb Clin Neurol. 2021;182:257-267. doi: 10.1016/B978-0-12-819973-2.00018-6.
Adang L, Goldbach-Mansky R, Vanderver A. JAK Inhibition in the Aicardi-Goutières Syndrome. Reply. N Engl J Med. 2020 Nov 26;383(22):2191-2193. doi: 10.1056/NEJMc2031081.
Lewis H, Samanta D, Örsell JL, Bosanko KA, Rowell A, Jones M, Dale RC, Taravath S, Hahn CD, Krishnakumar D, Chagnon S, Keller S, Hagebeuk E, Pathak S, Bebin EM, Arndt DH, Alexander JJ, Mainali G, Coppola G, Maclean J, Sparagana S, McNamara N, Smith DM, Raggio V, Cruz M, Fernández-Jaén A, Kava MP, Emrick L, Fish JL, Vanderver A, Helman G, Pierson TM, Zarate YA. Epilepsy and Electroencephalographic Abnormalities in SATB2-Associated Syndrome. Pediatr Neurol. 2020 Nov;112:94-100. doi: 10.1016/j.pediatrneurol.2020.04.006. Epub 2020 Apr 13.
Grineski SE, Morales DX, Collins T, Wilkes J, Bonkowsky JL. Racial/Ethnic and Insurance Status Disparities in Distance Traveled to Access Children's Hospital Care for Severe Illness: the Case of Children with Leukodystrophies. J Racial Ethn Health Disparities. 2020 Oct;7(5):975-986. doi: 10.1007/s40615-020-00722-w. Epub 2020 Feb 24.
Vanderver A, Adang L, Gavazzi F, McDonald K, Helman G, Frank DB, Jaffe N, Yum SW, Collins A, Keller SR, Lebon P, Meritet JF, Rhee J, Takanohashi A, Armangue T, Ulrick N, Sherbini O, Koh J, Peer K, Besnier C, Scher C, Boyle K, Dubbs H, Kramer-Golinkoff J, Pizzino A, Woidill S, Shults J. Janus Kinase Inhibition in the Aicardi-Goutières Syndrome. N Engl J Med. 2020 Sep 3;383(10):986-989. doi: 10.1056/NEJMc2001362.
Schmidt JL, Pizzino A, Nicholl J, Foley A, Wang Y, Rosenfeld JA, Mighion L, Bean L, da Silva C, Cho MT, Truty R, Garcia J, Speare V, Blanco K, Powis Z, Hobson GM, Kirwin S, Krock B, Lee H, Deignan JL, Westemeyer MA, Subaran RL, Thiffault I, Tsai EA, Fang T, Helman G, Vanderver A. Estimating the relative frequency of leukodystrophies and recommendations for carrier screening in the era of next-generation sequencing. Am J Med Genet A. 2020 Aug;182(8):1906-1912. doi: 10.1002/ajmg.a.61641. Epub 2020 Jun 23.
Vanderver A, Bernard G, Helman G, Sherbini O, Boeck R, Cohn J, Collins A, Demarest S, Dobbins K, Emrick L, Fraser JL, Masser-Frye D, Hayward J, Karmarkar S, Keller S, Mirrop S, Mitchell W, Pathak S, Sherr E, van Haren K, Waters E, Wilson JL, Zhorne L, Schiffmann R, van der Knaap MS, Pizzino A, Dubbs H, Shults J, Simons C, Taft RJ; LeukoSEQ Workgroup. Randomized Clinical Trial of First-Line Genome Sequencing in Pediatric White Matter Disorders. Ann Neurol. 2020 Aug;88(2):264-273. doi: 10.1002/ana.25757. Epub 2020 Jun 9.
Adang LA, Gavazzi F, Jawad AF, Cusack SV, Kopin K, Peer K, Besnier C, De Simone M, De Giorgis V, Orcesi S, Fazzi E, Galli J, Shults J, Vanderver A. Development of a neurologic severity scale for Aicardi Goutières Syndrome. Mol Genet Metab. 2020 Jun;130(2):153-160. doi: 10.1016/j.ymgme.2020.03.008. Epub 2020 Apr 2.
Helman G, Takanohashi A, Hagemann TL, Perng MD, Walkiewicz M, Woidill S, Sase S, Cross Z, Du Y, Zhao L, Waldman A, Haake BC, Fatemi A, Brenner M, Sherbini O, Messing A, Vanderver A, Simons C. Type II Alexander disease caused by splicing errors and aberrant overexpression of an uncharacterized GFAP isoform. Hum Mutat. 2020 Jun;41(6):1131-1137. doi: 10.1002/humu.24008. Epub 2020 Mar 11.
Wolf NI, Breur M, Plug B, Beerepoot S, Westerveld ASR, van Rappard DF, de Vries SI, Kole MHP, Vanderver A, van der Knaap MS, Lindemans CA, van Hasselt PM, Boelens JJ, Matzner U, Gieselmann V, Bugiani M. Metachromatic leukodystrophy and transplantation: remyelination, no cross-correction. Ann Clin Transl Neurol. 2020 Feb;7(2):169-180. doi: 10.1002/acn3.50975. Epub 2020 Jan 22.
Helman G, Lajoie BR, Crawford J, Takanohashi A, Walkiewicz M, Dolzhenko E, Gross AM, Gainullin VG, Bent SJ, Jenkinson EM, Ferdinandusse S, Waterham HR, Dorboz I, Bertini E, Miyake N, Wolf NI, Abbink TEM, Kirwin SM, Tan CM, Hobson GM, Guo L, Ikegawa S, Pizzino A, Schmidt JL, Bernard G, Schiffmann R, van der Knaap MS, Simons C, Taft RJ, Vanderver A. Genome sequencing in persistently unsolved white matter disorders. Ann Clin Transl Neurol. 2020 Jan;7(1):144-152. doi: 10.1002/acn3.50957. Epub 2020 Jan 7.
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