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Methylmalonic acidemia: brain lesions in a case of vitamin B12 non-responsive (mut0) type
K Yamaguchi1, K Hirabayashi, K Honma
1Department of Pediatrics, Higashi-Saitama National Hospital, Japan.
Abstract:
Neuropathological findings were described in a 9-day-old female infant who died of the vitamin B12 non-responsive (mut0) type of methylmalonic acidemia (MMA). Widespread karyorhectic fragments of varying size and shape were noted throughout the brain, in particular densely accumulated in the cerebellar granular layers and the layer IV of the striate cortex. Bilateral or symmetrical necrotic foci were observed in various regions of the grey matter: Sommer's sector of the hippocampus, basal ganglia, thalamus, hypothalamus and brainstem. In the cerebral cortex small spongy necrotic foci were scattered mainly in the depths of gyri. Alzheimer type II astrocytes appeared in the preserved zone of the caudate nucleus. Myelinated nerve fibers in the brainstem were spongy or vacuolated, whereas peripheral myelin sheaths of cranial nerves were intact. Multiple hemorrhagic foci were noted in the cerebellum, predominantly the granular layers. The lymphoid tissue in the spleen and the thymus was hypoplastic. It may be difficult to explain exactly the mechanisms of the pathological changes observed here on routine light microscopy; the outcome of systemic ischemia/hypoxia before death cannot be completely ignored. But, it is suggested that widespread karyorhexis may occur selectively in specific cells (or cell groups), including immature neurons and other cellular components (glial and/or mesenchymal cells) among the patients with the mut0 type of MMA.
Insights
Neuropathological examination of an infant with vitamin B12 non-responsive methylmalonic acidemia (MMA) revealed widespread cell death and brain lesions. These findings highlight the severe neurological impact of this metabolic disorder.
Area of Science:
- Neuropathology
- Metabolic Disorders
- Neuroscience
Background:
- Methylmalonic acidemia (MMA) is a group of inherited metabolic disorders.
- The vitamin B12 non-responsive (mut0) type of MMA presents unique challenges in understanding its pathogenesis.
- Infants with mut0 MMA often exhibit severe neurological complications.
Observation:
- A 9-day-old female infant with mut0 MMA exhibited widespread neuropathological changes.
- Key findings included karyorrhexis (cell fragmentation) in the cerebellum and striate cortex.
- Necrotic foci were observed in the hippocampus, basal ganglia, thalamus, hypothalamus, brainstem, and cerebral cortex.
Findings:
- Spongy degeneration of myelinated nerve fibers in the brainstem was noted.
- Alzheimer type II astrocytes were present in the caudate nucleus.
- Hemorrhagic foci were predominantly in the cerebellar granular layers, and lymphoid tissues were hypoplastic.
Implications:
- The study suggests selective karyorrhexis in specific cell types, including immature neurons, in mut0 MMA.
- While systemic ischemia/hypoxia cannot be ruled out, the findings point to intrinsic cellular mechanisms.
- Understanding these neuropathological mechanisms is crucial for potential therapeutic strategies in MMA.