Summary
Background: Glutaric aciduria type I (GA I) is an autosomal recessive disorder of lysine and tryptophan metabolism due to a deficiency in glutaryl-CoA dehydrogenase activity. Recent reports suggest that early diagnosis through newborn screening and initiation of preventive therapy result in improved functional outcome; however, detailed neuropsychological profiles of children with GA I are seldom reported and thus the impact of the disease on cognition, motor abilities and behaviour remains uncertain. Method: We present detailed neuropsychological profiles of three children who were diagnosed with GA I through newborn screening and treated from early age, and one asymptomatic patient diagnosed through cascade screening. A comprehensive battery of standardized tests was administered including measures of intellectual function, attention/memory, executive function, motor skills, speech/language, as well as behavioural and adaptive skills. Results: The results reveal overall average cognitive outcomes; however, subtle, but significant, fine motor and articulation deficits were observed. The results are discussed with regard to potential links between fine motor deficits and speech impairments in children with GA I. Such difficulties can impact on the child’s ability to engage in academic, leisure and daily activities. Conclusions: These findings highlight the importance of in-depth assessments of all aspects of neuropsychological function in patients with GA I and provide a basis for future neuropsychological assessment in similar groups of children. In spite of relatively preserved overall functioning, using a broad range of sensitive cognitive and motor measures facilitates the detection of subtle deficits, and allows for planning of early and adequate therapeutic interventions.
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Abbreviations
- ABAS-II:
-
Adaptive Behaviour Assessment System
- BRIEF-P/BRIEF:
-
Behavior Rating Inventory of Executive Function
- CBCL:
-
Child Behaviour Checklist
- GA I:
-
glutaric aciduria type I
- MABC-2:
-
Movement Assessment Battery for Children
- WPSSI-III:
-
Wechsler Preschool and Primary Intelligence Scale
References
Achenbach TM, Thomas M, Rescorla LA (2001) Manual for the ASEBA School-Age Forms and Profiles. Burlington, VT: University of Vermont, Research Center for Children, Youth, and Families.
Anderson P (2002) Assessment and development of executive function (EF) during childhood. Child Neuropsychol 8(2):71-82. doi:10.1076/chin.8.2.71.8724
Anderson V (2001) Assessing executive functions in children: biological, psychological, and developmental considerations. Pediatr Rehabil 4(3):119-136. doi:10.1080/13638490110091347
Anderson VA, Anderson P, Northam E, et al (2001) Development of executive functions through late childhood and adolescence in an Australian sample. Dev Neuropsychol 20(1):385-406. doi:10.1207/S15326942DN2001_5
Atkin N, Fisher J (1996) Articulation Survey. Melbourne: Royal Children’s Hospital.
Bishop DV (2002) Motor immaturity and specific speech and language impairment: evidence for a common genetic basis. Am J Med Genet 114(1):56-63. doi:10.1002/ajmg.1630
Boneh A, Beauchamp M, Humphrey M, et al (2008) Newborn screening for glutaric aciduria type I in Victoria: treatment and outcome. Mol Genet Metab 94(3):287-291. doi:10.1016/j.ymgme.2008.03.005
Breslau N (1990) Does brain dysfunction increased children’s vulnerability to environmental stress? Arch Gen Psychiatry 47(1):15-20.
Burlina AP, Zara G, Hoffmann GF, et al (2004) Management of movement disorders in glutaryl-CoA dehydrogenase deficiency: anticholinergic drugs and botulinum toxin as additional therapeutic options. J Inherit Metab Dis 27(6):911-915. doi:10.1023/B:BOLI.0000045776.50573.52
Dennis M (2000) Childhood medical disorders and cognitive impairment: biological risk, time, development, and reserve. In KO Yeates; MD Ris; HG Taylor; eds. Pediatric Neuropsychology: Research, Theory, and Practice. New York: Guilford Press, 3-22.
Dewey D (1993) Error analysis of limb and orofacial praxis in children with developmental motor deficits. Brain Cogn 23(2):203-221. doi:10.1006/brcg.1993.1055
Gioia GA, Isquith PK, Guy SC, et al (2000) Behavior Rating Inventory of Executive Function Professional Manual. Odessa, FL: Psychological Assessment Ressources.
Gioia GA, Espy KA, Isquith PK (2004) Behavior Rating Inventory of Executive Function Preschool Version Professional Manual. Lutz, FL: Psychological Assessment Ressources.
Groenewegen HJ (2003) The basal ganglia and motor control. Neural Plast 10(1-2):107-120. doi:10.1155/NP.2003.107
Harrison PL, Oakland T (2003) Adaptive Behavior Assessment System – Second Edition. San Antonio, TX: The Psychological Corporation.
Henderson SE, Sugden DA, Barnett AL (2007) Movement Assessment Battery for Children – Second Edition. London: Harcourt Assessment.
Hill EL (2001) Non-specific nature of specific language impairment: a review of the literature with regard to concomitant motor impairments. Int J Lang Commun Disord 36(2):149-171. doi:10.1080/13682820010019874
Hoffmann GF, Athanassopoulos S, Burlina AB, et al (1996) Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics 27(3):115-123. doi:10.1055/s-2007-973761
Kölker S, Greenberg CR, Lindner M, et al (2004) Emergency treatment in glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis 27(6):893-902. doi:10.1023/B:BOLI.0000045774.51260.ea
Kölker S, Garbade SF, Greenberg CR, et al (2006a) Natural history, outcome, and treatment efficacy in children and adults with glutaryl-CoA dehydrogenase deficiency. Pediatr Res 59(6):840-847. doi:10.1203/01.pdr.0000219387.79887.86
Kölker S, Sauer SW, Surtees RA, et al (2006b) The aetiology of neurological complications of organic acidaemias—a role for the blood–brain barrier. J Inherit Metab Dis 29(6):701-704; discussion 705-706. doi:10.1007/s10545-006-0415-8
Kölker S, Christensen E, Leonard JV, et al (2007) Guideline for the diagnosis and management of glutaryl-CoA dehydrogenase deficiency (glutaric aciduria type I). J Inherit Metab Dis 30(1):5-22. doi:10.1007/s10545-006-0451-4
Korkman M, Kirk U, Kemp S (2007) NEPSY-II: A Developmental Neuropsychological Assessment. San Antonio, TX: The Psychological Corporation.
Kyllerman M, Skjeldal O, Christensen E, et al (2004) Long-term follow-up, neurological outcome and survival rate in 28 Nordic patients with glutaric aciduria type 1. Eur J Paediatr Neurol 8(3):121-129. doi:10.1016/j.ejpn.2003.12.007
Kyllerman M, Skjeldal OH, Lundberg M, et al (1994) Dystonia and dyskinesia in glutaric aciduria type I: clinical heterogeneity and therapeutic considerations. Mov Disord 9(1):22-30. doi:10.1002/mds.870090105
Lindner M, Kölker S, Schulze A, et al (2004) Neonatal screening for glutaryl-CoA dehydrogenase deficiency. J Inherit Metab Dis 27(6):851-859. doi:10.1023/B:BOLI.0000045769.96657.af
Naughten ER, Mayne PD, Monavari AA, et al (2004) Glutaric aciduria type I: outcome in the Republic of Ireland. J Inherit Metab Dis 27(6):917-920. doi:10.1023/B:BOLI.0000045777.82784.74
Newmeyer AJ, Grether S, Grasha C, et al (2007) Fine motor function and oral-motor imitation skills in preschool-age children with speech-sound disorders. Clin Pediatr (Phila) 46(7):604-611. doi:10.1177/0009922807299545
Patil N, Shinde S, Karande S, et al (2004) Glutaric aciduria type I associated with learning disability. Indian J Pediatr 71(10):948.
Sauer SW, Okun JG, Fricker G, et al (2006) Intracerebral accumulation of glutaric and 3-hydroxyglutaric acids secondary to limited flux across the blood–brain barrier constitute a biochemical risk factor for neurodegeneration in glutaryl-CoA dehydrogenase deficiency. J Neurochem 97(3):899-910. doi:10.1111/j.1471-4159.2006.03813.x
Simons A, Eyskens F, De Groof A, et al (2006) Cognitive functioning and psychiatric disorders in children with a metabolic disease. Eur Child Adolesc Psychiatry 15(4):207-213. doi:10.1007/s00787-006-0524-9
Strauss KA, Morton DH (2003) Type I glutaric aciduria, part 2: a model of acute striatal necrosis. Am J Med Genet C Semin Med Genet 121C(1):53-70. doi:10.1002/ajmg.c.20008
Strauss KA, Puffenberger EG, Robinson DL, et al (2003) Type I glutaric aciduria, part 1: natural history of 77 patients. Am J Med Genet C Semin Med Genet 121C(1):38-52. doi:10.1002/ajmg.c.20007
Strauss KA, Lazovic J, Wintermark M, et al (2007) Multimodal imaging of striatal degeneration in Amish patients with glutaryl-CoA dehydrogenase deficiency. Brain 130(Pt 7):1905-1920. doi:10.1093/brain/awm058
Superti-Furga A, Hoffmann GF (1997) Glutaric aciduria type 1 (glutaryl-CoA-dehydrogenase deficiency): advances and unanswered questions. Report from an international meeting. Eur J Pediatr 156(11):821-828. doi:10.1007/s004310050721
Wechsler D (2002) The Wechsler Preschool and Primary Scale of Intelligence – Third Edition (WPSSI-III). London: The Psychological Corporation.
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We thank Ms Louise Crossley for her help in conducting the assessments.
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Communicating editor: Georg Hoffmann
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Beauchamp, M.H., Boneh, A. & Anderson, V. Cognitive, behavioural and adaptive profiles of children with glutaric aciduria type I detected through newborn screening. J Inherit Metab Dis 32 (Suppl 1), 207–213 (2009). https://doi.org/10.1007/s10545-009-1167-z
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DOI: https://doi.org/10.1007/s10545-009-1167-z