Approach to neurometabolic diseases from a pediatric neurological point of view

Abstract

Objective Neurometabolic disorders are an important group of diseases that mostly are presented in newborns and infants. Neurological manifestations are the prominent signs and symptoms in this group of diseases. Seizures are a common sign and are often refractory to antiepileptic drugs in untreated neurometabolic patients. The onset of symptoms for neurometabolic disorders appears after an interval of normal or near normal growth and development.Additionally, affected children may fare well until a catabolic crisis occurs. Patients with neurometabolic disorders during metabolic decompensation have severe clinical presentation, which include poor feeding, vomiting, lethargy, seizures, and loss of consciousness. This symptom is often fatal but severe neurological insult and regression in neurodevelopmental milestones can result as a prominent sign in patients who survived. Acute symptoms should be immediately treated regardless of the cause. A number of patients with neurometabolic disorders respond favorably and, in some instances, dramatically respond to treatment. Early detection and early intervention is invaluable in some patients to prevent catabolism and normal or near normal neurodevelopmental milestones. This paper discusses neurometabolic disorders, approaches to this group of diseases (from the view of a pediatric neurologist), clinical and neurological manifestations, neuroimaging and electroencephalography findings, early detection, and early treatment.

Keywords: Early detection; Early treatment; Electroencephalography; Neurological manifestation; Neurometabolic disorders.

Fig 1

Abnormally high signal intensity in white matter regions around the anterior and posterior horns of both lateral ventricles and brain atrophy in phenylketonuria

Fig 2

Single proton MR spectroscopy shows the presence of branched-chain amino acids resonating at 0.9–1.0 ppm

Fig 3

Abnormal Signal in Bilateral Basal Ganglia and Brain Atrophy in an MRI from a 4-year-old boy with propionic-acidemia

Fig 4

Severe brain atrophy in a patient with biotinidase deficiency

Fig 5

MRS in a patient with Canavan disease shows a markedly increased level of N-acetylaspartic acid (NAA)

Fig 6

Cranial MRI and MRS in a patient with glutaric aciduria type I and Axial MRI shows an abnormal signal in bilateral basal ganglia with bilateral prominent sylvian fissures

Fig 7

Burst suppression patterns in a 4.5-month-old infant with early myoclonic encephalopathy

Fig 8

Hypsarrhythmia patterns with mixed asynchronous slow waves and spike waves in an 8.5-month-old infant with West syndrome

Fig 9

Slow spike waves with fast spike components in a 13-year-old boy with Unverricht-Lundborg Syndrome