Neurological dysfunction is an important manifestation of inherited metabolic disorders.

• Abstract
• Introduction
• Chronic Encephalopathy
• Acute Encephalopathy
• Ataxia and Extrapyramidal Movement Disorders
• Myopathy
• Psychiatric problems
• Biochemical investigations
• Glucose
• Blood Gases and Acid-base Profile
• Lactate
• Ketones
• Ammonium
• Amino acids
• Organic acids
• Mucopolysaccharides
• Oligosaccharides
• Acylcarnitine and acylglycines
• Very-long-chain fatty acids (VLCFA)
• Red Cell Plasmalogens
• Pipecolic acid
• Enzyme studies
• Tandem mass spectrometry
• Molecular genetic studies
• Neuroimaging
• Treatment of inherited neurometabolic disorders
• Conclusion
• References
• Figures
• Tables

MR imaging has emerged as a powerful tool in the study of normal and abnormal brain structure, function and biochemistry. Clinicians can derive significant benefits from specific imaging findings in neurometabolic disorders.^[36] Some of the neurometabolic disorders with typical neuroimaging manifestations are phenylketonuria, maple syrup urine disease, glutaric aciduria type I and methylmalonic acidemia. Although urea cycle disorders are not associated with specific imaging findings, hyperammonemia resulting from these disorders can lead to typical findings and facilitate diagnosis.^[37] In classical phenylketonuria, white matter abnormalities are frequently observed. The earliest and most frequent abnormalities are high signal-intensity lesions on T2-weighted images in the parieto-occipital periventricular white matter (periatrial and peritrigonal regions)^[38][Figure 6]. The white matter lesions are symmetrical and either band-like or patchy and partly confluent in an irregular fashion. Frequently, the frontal, and less often, the occipital white matter changes have a peculiar configuration that extends like a small flame from the ventricular border in line with the ventricle.^[39]

In maple syrup urine disease, MRI shows diffuse symmetrical hyperintensities involving the periventricular, deep white matter and subcortical 'U' fibers^[40][Figure 7]. The other areas involved are the globus pallidus, thalami and brainstem. The globus pallidus showed diffuse involvement, but the involvement of the thalami was limited mainly to the anterolateral region, sparing the dorsomedial and dorsolateral regions. In the cerebellum, the deep white matter as well as the dentate nuclei shows T2 hyperintensities. In the intermediate form of MSUD, there may be sparing of posterior limb of the internal capsule.^[41] Proton MRS is particularly helpful in establishing a diagnosis during metabolic decompensation. A peak is observed at 0.9 PPM, which results from the resonance of the branched-chain amino acids and keto acids.

Organic acidemias are another group of disorders with characteristic neuroimaging findings, which aid in diagnosis. Widening of the sylvian fissure, mesencephalic cistern and expansion of CSF spaces anterior to the temporal lobes are cardinal signs of glutaric aciduria Type-1 [Figure 8]. If combined with abnormalities of the basal ganglia and white matter, glutaric aciduria Type-1 should be strongly suspected.^[42] In some patients, delayed myelination or white matter abnormalities are noted.^[43],[44]

The characteristic feature of methylmalonic acidemia is severe involvement of the globus pallidus^[45],[46][Figure 9]. The bilateral pallidal necrosis as revealed by neuroimaging occurs due to acute respiratory acidosis with cell necrosis. Involvement of other ganglionic structures is usually not noted. There is no definite explanation for the selective involvement of globus pallidus in methylmalonic acidemia. This finding is noted both in individuals with acute decompensation and in those without such episodes.