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Neurometabolic Disorders

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Clinical Child Neurology

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Abstract

Inborn errors of metabolism (IEM) are inherited diseases that result mainly from single gene defects leading to deficiency of a protein in the form of an enzyme or a cofactor. Neurometabolic disorders constitute a group of IEM that present with predominant neurological manifestations if untreated. Broadly, neurometabolic disorders can be classified into three major groups: disorders of intermediary metabolism, disorders of complex molecules, and neurotransmitter disorders. Neurometabolic disorders may affect a specific part of the central or peripheral nervous system such as extrapyramidal tracts, basal ganglia, spinal cord, or lower motor unit. They present with a variety of neurological symptoms and signs. These range from isolated epilepsy to constellation of features suggestive of acute encephalopathy, chronic encephalopathy, and/or movement disorder. When a neurometabolic disease is suspected, baseline investigations such as blood gas, glucose, lactate, and ammonia may direct the physician toward the possible etiology of the disease. Further investigations like serum amino acids, acylcarnitine profile, and urine organic acids may pinpoint the diagnosis, which may ultimately be confirmed by an enzyme assay or a molecular study. Early diagnosis and appropriate management of neurometabolic disorders are often associated with a favorable outcome, especially in the neonatal period. Effective management strategies may include supportive care, removal of toxic metabolites, and provision of adequate calories and dietary intervention, together with introduction of specific drugs, chaperones, enzyme replacement therapy, and stem cell and liver transplant when indicated.

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Change history

  • 11 October 2020

    The original version of this chapter was revised and erratum as followed by

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Authors and Affiliations

  1. Division of Genetics/Metabolic, Department of Pediatrics, Prince Sultan Military Medical City, Riyadh, Saudi Arabia

    Sarar Mohamed

  2. Prince Abdullah bin Khalid Celiac Disease Research Chair, Vice Deanship of Scientific Research chairs, King Saud University, Riyadh, Saudi Arabia

    Sarar Mohamed

  3. Department of Pediatrics, College of Medicine, AlFaisal University, Riyadh, Saudi Arabia

    Sarar Mohamed

  4. Division of Pediatric Neurology, Department of Pediatrics, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia

    Mustafa A. M. Salih

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  1. Sarar Mohamed
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Correspondence to Sarar Mohamed .

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  1. College of Medicine Division of Pediatric Neurology, King Saud University, Riyadh, Saudi Arabia

    Mustafa A.M. Salih

14.1 Electronic Supplementary Material

Video EEG of a baby with nonketotic hyperglycinemia manifesting infantile epileptic encephalopathy and hiccups. The baby was unconscious and the record showed prolonged suppression followed by a short period of bursts of generalized discharges of spikes/polyspikes and sharp waves and slow waves (burst-suppression pattern) associated with violent flexor spasms. Inter-burst-interval (suppression period) was much longer and the baby was motionless. In one occasion, the baby developed tonic posturing of the right hand with continuous ictal discharges on the left hemisphere followed by complete inactivation in the right upper limb (MPG 12818 kb)

A baby with GM2 Gangliosidosis (Sandhoff disease) showing ankle clonus as a feature of hyperreflexia (AVI 12060 kb)

A child with GM2 Gangliosidosis (Tay-Sachs disease) showing startle reactions to loud sound (AVI 9475 kb)

Choreic movements in a child with neuronal ceroid lipofuscinosis (CLN) type 7 (CLN7) (AVI 3008 kb)

Myoclonic jerks in a child with neuronal ceroid lipofuscinosis (CLN) type 14 (CLN14) (AVI 14605 kb)

Hyperekplexia in a neonate with neuronal ceroid lipofuscinosis (CLN) type 10 (CLN10). There is remarkable exaggerated startle to tactile and acoustic stimuli (tapping the nose, touch, and sound) (MPG 49012 kb)

A child with Lesch-Nyhan syndrome showing extrapyramidal signs in the form of very large amplitude, jerky gross motor movements (ballism). The left upper limb was stranded to prevent self-injury (AVI 3327 kb)

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Mohamed, S., Salih, M.A.M. (2020). Neurometabolic Disorders. In: Salih, M.A. (eds) Clinical Child Neurology. Springer, Cham. https://doi.org/10.1007/978-3-319-43153-6_14

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