Neurological Involvement in Inherited Metabolic Diseases: An Overview

Abstract

Neurological involvement is a typical feature of several inherited metabolic diseases. The onset of signs and/or symptoms may appear as early as the first days of life or after an interval of normal or near-normal growth and development. Metabolic decomposition usually presents with a severe clinical phenotype, which include poor feeding, vomiting, lethargy, seizures, and loss of consciousness. This spectrum of manifestations is often fatal; however, severe neurological sequelae and/or regression of neurodevelopmental milestones can be the prominent signs in those who survive. Overall, treatable inborn errors of metabolism can be divided in three groups, namely: (Group 1) inborn errors of intermediary metabolism giving rise to acute or chronic intoxication; (Group 2) inborn errors of intermediary metabolism affect in genergetic processes; and (Group 3) inborn errors involving cellular organelles, including lysosomal, peroxisomal, glycosylation, and cholesterol synthesis defects. The spectrum of neurological manifestations includes developmental delay, seizures and epilepsy, pyramidal and extrapyramidal signs, movement disorders, vision and hearing impairment, peripheral neuropathy, and psychiatric abnormalities. The main anatomical/imaging patterns reflects selective vulnerability of nervous system substance and include atrophy, (predominantly) symmetrical abnormalities, and dysmyelination, As several patients with neurometabolic diseases responds favorably to therapeutic trials, early detection and early intervention is of utmost importance to prevent catabolic-related damage and to revert to normal or near-normal parameters neurodevelopmental milestones.

Keywords

inherited metabolic diseases - neurometabolic disorders - classification - neurological - imaging - therapy

• References

• 1 Saudubray JM, Sedel F, Walter JH. Clinical approach to treatable inborn metabolic diseases: an introduction. J Inherit Metab Dis 2006; 29 (2–3) 261-274
• 2 Saudubray JM, Nassogne MC, de Lonlay P, Touati G. Clinical approach to inherited metabolic disorders in neonates: an overview. Semin Neonatol 2002; 7 (1) 3-15
• 3 Lyon G, Adams RD, Kolodny EH. Neurology of Hereditary Metabolic Diseases of Children. 2nd ed. New York, NY: McGraw-Hill; 2001
• 4 Brusilow SW. Urea cycle enzymes. In: Scriver CR, Beaudet AL, Sly WS, Valle D, eds. The Metabolic and Molecular Bases of Inherited Disease. 8th ed. New York, NY: McGraw-Hill; 2001: 1909-1963
• 5 Surtees R, Leonard JV. Acute metabolic encephalopathy: a review of causes, mechanisms and treatment. J Inherit Metab Dis 1989; 12 (Suppl. 01) 42-54
• 6 Wallace DC. Animal models for mitochondrial disease. Methods Mol Biol 2002; 197: 3-54
• 7 Tomanin R, Zanetti A, D'Avanzo F , et al. Clinical efficacy of enzyme replacement therapy in paediatric Hunter patients, an independent study of 3.5 years. Orphanet J Rare Dis 2014; 9: 129
• 8 Sechi A, Deroma L, Dardis A , et al. Long term effects of enzyme replacement therapy in an Italian cohort of type 3 Gaucher patients. Mol Genet Metab 2014; 113 (3) 213-218
• 9 Concolino D, Degennaro E, Parini R ; Fabry Delphi working group; Fabry Delphi working group. Delphi consensus on the current clinical and therapeutic knowledge on Anderson-Fabry disease. Eur J Intern Med 2014; 25 (8) 751-756
• 10 Spronsen FJ, Smit GPA, Erwich JJHM. Inherited metabolic diseases and pregnancy. BJOG 2005; 112 (1) 2-11
• 11 Saudubray JM. A clinical approach to inherited metabolic diseases. In: Fernandes J, Saudubray JM, van den Berghe G, eds. Inborn Metabolic Diseases: Diagnosis and Treatment. Heidelberg: Springer MedizinVerlag; 2006: 33-47
• 12 García-Cazorla A, Wolf NI, Serrano M , et al. Mental retardation and inborn errors of metabolism. J Inherit Metab Dis 2009; 32 (5) 597-608
• 13 Pavone P, Spalice A, Polizzi A, Parisi P, Ruggieri M. Ohtahara syndrome with emphasis on recent genetic discovery. Brain Dev 2012; 34 (6) 459-468
• 14 Dulac O, Plecko B, Gataullina S, Wolf NI. Occasional seizures, epilepsy, and inborn errors of metabolism. Lancet Neurol 2014; 13 (7) 727-739
• 15 Pavone P, Striano P, Falsaperla R, Pavone L, Ruggieri M. Infantile spasms syndrome, West syndrome and related phenotypes: what we know in 2013. Brain Dev 2014; 36 (9) 739-751
• 16 García-Cazorla A, Wolf NI, Serrano M , et al. Inborn errors of metabolism and motor disturbances in children. J Inherit Metab Dis 2009; 32 (5) 618-629
• 17 Singer HS, Mink JW, Gilbert DL, Jankovic J. Movement Disorders in Childhood. Philadelphia. PA: Saunders/Elsevier; 2010
• 18 Del Balzo F, Spalice A, Ruggieri M, Greco F, Properzi E, Iannetti P. Stroke in children: inherited and acquired factors and age-related variations in the presentation of 48 paediatric patients. Acta Paediatr 2009; 98 (7) 1130-1136
• 19 Pavone P, Incorpora G, Fiumara A, Parano E, Trifiletti RR, Ruggieri M. Epilepsy is not a prominent feature of primary autism. Neuropediatrics 2004; 35 (4) 207-210
• 20 Manzi B, Loizzo AL, Giana G, Curatolo P. Autism and metabolic diseases. J Child Neurol 2008; 23 (3) 307-314
• 21 Zecavati N, Spence SJ. Neurometabolic disorders and dysfunction in autism spectrum disorders. Curr Neurol Neurosci Rep 2009; 9 (2) 129-136
• 22 Arsov T, Mullen SA, Damiano JA , et al. Early onset absence epilepsy: 1 in 10 cases is caused by GLUT1 deficiency. Epilepsia 2012; 53 (12) e204-e207
• 23 Parolin G, Drigo P, Toldo I , et al. Pre- and postprandial electroencephalography in glucose transporter type 1 deficiency syndrome: an illustrative case to discuss the concept of carbohydrate responsiveness. J Child Neurol 2011; 26 (1) 103-108
• 24 Veldman A, Santamaria-Araujo JA, Sollazzo S , et al. Successful treatment of molybdenum cofactor deficiency type A with cPMP. Pediatrics 2010; 125 (5) e1249-e1254
• 25 Van der Knaap M, Valk J. Magnetic Resonance of Myelination and Myelin Disorders. 3rd ed. Berlin: Springer-Verlag; 2005
• 26 Patay Z. Metabolic disorders. In: Tortori-Donati P, Rossi A, eds. Pediatric Neuroradiology. Brain. Berlin: Springer-Verlag; 2005: 543-722
• 27 Barkovich AJ. Pediatric Neuroradiology. 5th ed. Baltimore, MD: Lippincott Williams & Wilkins; 2010
• 28 Pavone P, Pettoello-Mantovano M, Le Pira A , et al. Acute disseminated encephalomyelitis: a long-term prospective study and meta-analysis. Neuropediatrics 2010; 41 (6) 246-255
• 29 Ruggieri M, Polizzi A, Pavone L, Musumeci S. Thalamic syndrome in children with measles infection and selective, reversible thalamic involvement. Pediatrics 1998; 101 (1, Pt 1): 112-119
• 30 Ruggieri M, Tigano G, Mazzone D, Tiné A, Pavone L. Involvement of the white matter in hypomelanosis of Ito (incontinentia pigmenti achromiens). Neurology 1996; 46 (2) 485-492
• 31 Therrell Jr BL, Lloyd-Puryear MA, Camp KM, Mann MY. Inborn errors of metabolism identified via newborn screening: ten-year incidence data and costs of nutritional interventions for research agenda planning. Mol Genet Metab 2014; 113 (1–2) 14-26