Neuropsychological Development in Patients with Long-Chain 3-Hydroxyacyl-CoA Dehydrogenase (LCHAD) Deficiency
Background: Reports on cognitive outcomes in long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) are scarce. We present results from neuropsychological assessments of eight patients diagnosed with LCHADD prior to newborn screening with regard to clinical disease severity.
Methods: Intellectual ability and adaptive and executive functions were assessed using age-appropriate Wechsler Scales, Adaptive Behavior Assessment Scales (ABAS), and Behavior Rating Inventory of Executive Function (BRIEF).
Results: Five patients performed in the normal range on IQ tests but with lower scores on verbal working memory. In addition, they had lower parent-rated adaptive and executive functions.
Three patients had intellectual disabilities with IQs below normal and/or autism spectrum disorders. In addition, they had low results on parent-rated adaptive functions. (Two of these patients had epilepsy.)
Conclusions: Patients with LCHADD seem to have a specific cognitive pattern, with presentation as intellectual disability and specific autistic deficiencies or a normal IQ with weaknesses in auditive verbal memory and adaptive and executive functions. Future studies are warranted to investigate whether newborn screening programs and early treatment may promote improved neuropsychological development and outcomes.
KeywordsBeta-oxidation disorder Children Cognitive outcome Cognitive profile Fatty acid oxidation disorder Inborn error of metabolism LCHAD Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency Neuropsychological development
Adaptive Behavior Assessment System®
Autism spectrum disorder
Behavior Rating Inventory of Executive Function®
Fatty acid oxidation defect
General Adaptive Composite
Global executive function
Long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency
Mitochondrial trifunctional protein
We are greatly indebted to all the families who participated in the study and to all our collaborators at the Center for Inherited Metabolic Diseases for skillful laboratory knowledge. The study was supported by grants from the regional agreement on medical training and clinical research (ALF) between Stockholm County Council and the Karolinska Institute and Uppsala County and Uppsala University, the Swedish Order of Freemasons (Frimurare Barnhuset), HRH Crown Princess Lovisa’s Association for Child Medical Care (HKH Kronprinsessan Lovisas förening för barnasjukvård), and the Swedish Neuropsychological Society.
- APA DSM IV (2000) Diagnostic and statistical manual of mental disorders, 4th edn. American Psychiatric Association, Washington, DCGoogle Scholar
- Carver JD, Benford VJ, Han B, Cantor AB (2001) The relationship between age and the fatty acid composition of cerebral cortex and erythrocytes in human subjects. Brain Res Bull 56:79–85Google Scholar
- Gioia GA, Isquith PK, Guy SC, Kenworthy L (2000) Behavior rating inventory of executive function. Psychological Assessment Resources, OdessaGoogle Scholar
- Harrison PL, Oakland T (2003) Swedish version (2008) Adaptive behavior assessment system – ABAS-II. Harcourt Assessment, Stockholm Pearson Assessment, San AntonioGoogle Scholar
- Wechsler D (1997) Swedish version (2003) WAIS-III: Wechsler adult intelligence scale, 3rd edn. The Psychological Corporation, San AntonioGoogle Scholar
- Wechsler D (2002) Swedish version (2005) WPPSI-III: Wechsler preschool and primary scale of intelligence, 3rd edn. Psychological Corporation, San AntonioGoogle Scholar
- Wechsler D (2004) Swedish version (2007) WISC-IV: the Wechsler intelligence scale for children, 4th edn. Pearson Assessment, LondonGoogle Scholar
- Wechsler D (2008) Swedish version (2010) WAIS-IV: Wechsler adult intelligence scale, 4th edn. Pearson Assessment, LondonGoogle Scholar
- Wechsler D, Naglieri JA (2006) Swedish version (2007). WNV: Wechsler nonverbal scale of ability. Harcourt Assessment, StockholmGoogle Scholar