Cerebral Lipid Accumulation Detected by MRS in a Child with Carnitine Palmitoyltransferase 2 Deficiency: A Case Report and Review of the Literature on Genetic Etiologies of Lipid Peaks on MRS

Abstract

The majority of lipids in the brain are located in the bilayer membranes. These lipids are not visible by magnetic resonance spectroscopy since they have restricted mobility. Only mobile lipids, such as cholesterol esters or triglycerides in neutral lipid droplets, have enough rotational freedom to generate a signal on spectroscopy. These signals are detected as peaks at 1.3 ppm, originating from the methylene groups in the fatty acid chain, and 0.9 ppm, originating from the distal methyl group. We review the literature on the different genetic conditions that have been found to show lipid peaks on brain spectroscopy and report the first patient with carnitine palmitoyltransferase 2 deficiency shown to have such lipid peaks, thus indicating brain fat accumulation.

Metabolic Evaluation of Epilepsy: A Diagnostic Algorithm With Focus on Treatable Conditions

“…Certain IEMs can be accompanied by structural brain anomalies identifiable by brain MRI, such as a dysgenetic corpus callosum seen commonly in patients with pyruvate dehydrogenase complex deficiency or glycine encephalopathy (23). Brain magnetic resonance spectroscopy can sometimes point toward the right diagnosis, as has been reported in patients with GABA transaminase deficiency (24), fatty acid oxidation disorders (25), mitochondrial disease or glycine encephalopathy (26). Table 2 provides a summary of the salient clinical, laboratory, electrographic, and neuroimaging finding of the most common metabolic epilepsies.…”

Aberrant interactions of peripheral measures and neurometabolites with lipids in complex regional pain syndrome using magnetic resonance spectroscopy: A pilot study

“…The main spectroscopy peaks at 1.3 ppm originate from the methylene groups in the fatty acid chain, while those at 0.9 ppm originate from distal methyl groups. 10 We reported elevated neuroinflammation throughout the basal ganglia and some cortical regions in CRPS patients in a previous study 3 and found an association between lipids in brains and neuroinflammation. Mobile lipids visible on MRS can be seen in various acquired disorders, such as areas of necrosis within brain tumors, 12 and demyelinating diseases, such as multiple sclerosis.…”

“…Only mobile lipids in neutral lipid droplets have sufficient rotational freedom to generate a signal on spectroscopy; these signals are detected as peaks at 1.3 ppm, originating from the methylene groups in the fatty acid chain, and at 0.9 ppm, originating from distal methyl groups. 10 We reported increased neuroinflammation throughout the basal ganglia and some cortical regions in CRPS patients in a previous study 3 and found an association between lipids in the brain and neuroinflammation. Considering that the somatosensory system involved in pain perception includes the thalamus, the primary somatosensory cortex, and the insula 11 and that the thalamus is the region that connects peripheral regions directly, we focused on the right and left thalamic regions.…”

“…Furthermore, Lip13a and Lip09 levels in the thalamus may be differently associated with peripheral measures, depending on the side of the thalamus involved (right or left), in healthy controls, and CRPS patients. Although Lip13a and Lip09 are identical lipids and the increase in necrosis-dependent lipid signals 4 may be associated with CRPS, the differences between Lip13a and Lip09 in terms of the methylene and methyl groups 10 may differently be associated with neuroinflammation in the right and left thalamus in CRPS patients. Thus, the different associations between Lip13a and Lip09 with complex pathological mechanisms in CRPS need to be confirmed according to their activities in the right and left thalamus and their interactions with peripheral measures.…”

Weak neuronal glycolysis sustains cognition and organismal fitness

“…2e), and in vivo 1 H-MRS brain analysis of CamkIIα-Pfkfb3 mice showed increased lipid 13a and lipid 13b signals (Extended Data Fig. 3b), which denotes enhanced abundance of lipid droplets 29,30 . To confirm this, we assessed by western blotting the levels of perilipin 2 (PLIN2), a lipid droplet-coating protein that limits the access of lipases, favouring the accumulation of lipids 31 .…”