ABSTRACT
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.
ABSTRACT
Children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. Knowledge on substrate metabolism in children with LCHAD deficiency during fasting is limited. Treatment guidelines differ between centers, both as far as length of fasting periods and need for night feeds are concerned. To increase the understanding of fasting intolerance and improve treatment recommendations, children with LCHAD deficiency were investigated with stable isotope technique, microdialysis, and indirect calometry, in order to assess lipolysis and glucose production during 6 h of fasting. We found an early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia. The rate of glycerol production, reflecting lipolysis, averaged 7.7 ± 1.6 µmol/kg/min, which is higher compared to that of peers. The rate of glucose production was normal for age; 19.6 ± 3.4 µmol/kg/min (3.5 ± 0.6 mg/kg/min). Resting energy expenditure was also normal, even though the respiratory quotient was increased indicating mainly glucose oxidation. The results show that lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested.
Subject(s)
3-Hydroxyacyl CoA Dehydrogenases/deficiency , Cardiomyopathies/enzymology , Energy Metabolism , Fasting/blood , Lipid Metabolism, Inborn Errors/enzymology , Lipolysis , Mitochondrial Myopathies/enzymology , Nervous System Diseases/enzymology , Rhabdomyolysis/enzymology , 3-Hydroxyacyl CoA Dehydrogenases/blood , Age Factors , Biomarkers/blood , Blood Glucose/metabolism , Calorimetry, Indirect , Cardiomyopathies/blood , Cardiomyopathies/diagnosis , Cardiomyopathies/diet therapy , Carnitine/analogs & derivatives , Carnitine/blood , Child , Child, Preschool , Female , Glycerol/blood , Humans , Hyperglycemia/blood , Hyperglycemia/diagnosis , Hyperglycemia/enzymology , Isotope Labeling , Lipid Metabolism, Inborn Errors/blood , Lipid Metabolism, Inborn Errors/diagnosis , Lipid Metabolism, Inborn Errors/diet therapy , Male , Microdialysis , Mitochondrial Myopathies/blood , Mitochondrial Myopathies/diagnosis , Mitochondrial Myopathies/diet therapy , Mitochondrial Trifunctional Protein/deficiency , Nervous System Diseases/blood , Nervous System Diseases/diagnosis , Nervous System Diseases/diet therapy , Postprandial Period , Rhabdomyolysis/blood , Rhabdomyolysis/diagnosis , Rhabdomyolysis/diet therapy , Time FactorsABSTRACT
UNLABELLED: Long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency is an inborn error of fatty acid metabolism that affects the degradation of long chain fatty acids and causes insufficient energy production and accumulation of toxic intermediates. The treatment consists of a diet low in fat, with supplementation of medium-chain triglycerides that bypass the metabolic block. In addition, frequent feeds and extra carbohydrates are given during febrile illnesses to reduce lipolysis. Hence, this diet differs from the general dietary recommendations for growing children. Furthermore, the Swedish dietary instructions for fat intake in LCHAD deficiency are given in grams, which differ from most guidelines that recommend fat intake as percentage shares of total caloric intake. AIMS: To assess growth in patients with LCHAD deficiency, in relation to dietary treatment and to evaluate if overweight/obesity is more common than in the normal population. RESULTS: The growth velocity showed acceleration after diagnosis and the start of treatment, followed by a period of stable or decelerated growth. The majority of the patients developed overweight to a greater extent than children without LCHAD deficiency. Several patients also went through a phase of obesity. Data on final height (FH) showed that three out of five patients had grown according to their genetic potential. CONCLUSIONS: Regular and frequent follow-up and careful monitoring of weight are essential to avoid the development of overweight and obesity. The Swedish dietary instructions defining fat intake in total grams per day may be an alternative approach to achieve a moderate total caloric intake.
