MTP deficiency caused by HADHB mutations: Pathophysiology and clinical manifestations
| Autor: | Benoit J. Gentil, Rami Massie, Robin Dagher |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Endocrinology Diabetes and Metabolism Cardiomyopathy Schwann cell Mitochondrial trifunctional protein 030105 genetics & heredity Biochemistry Lipid Metabolism Inborn Errors Rhabdomyolysis 03 medical and health sciences 0302 clinical medicine Endocrinology Internal medicine Genetics medicine Humans Myopathy Molecular Biology biology business.industry Mitochondrial Trifunctional Protein Hypoketotic hypoglycemia Mitochondrial Myopathies medicine.disease medicine.anatomical_structure Peripheral neuropathy Phenotype Mitochondrial Trifunctional Protein beta Subunit Mutation biology.protein medicine.symptom Nervous System Diseases business Cardiomyopathies 030217 neurology & neurosurgery HADHB |
| Zdroj: | Molecular genetics and metabolism. 133(1) |
| ISSN: | 1096-7206 |
| Popis: | Mutations in the HADHB gene lead to Mitochondrial Trifunctional Protein (MTP) deficiency. MTP deficiency is a rare autosomal recessive disorder affecting long-chain fatty acid oxidation. Patients affected by MTP deficiency are unable to metabolize long-chain fatty-acids and suffer a variety of symptoms exacerbated during fasting. The three phenotypes associated with complete MTP deficiency are an early-onset cardiomyopathy and early death, an intermediate form with recurrent hypoketotic hypoglycemia and a sensorimotor neuropathy with episodic rhabdomyolysis with small amount of residual enzyme activities. This review aims to discuss the pathophysiological mechanisms and clinical manifestations of each phenotype, which appears different and linked to HADHB expression levels. Notably, the pathophysiology of the sensorimotor neuropathy is relatively unknown and we provide a hypothesis on the qualitative aspect of the role of acylcarnitine buildup in Schwann cells in MTP deficiency patients. We propose that acylcarnitine may exit the Schwann cell and alter membrane properties of nearby axons leading to axonal degeneration based on recent findings in different metabolic disorders. |
| Databáze: | OpenAIRE |
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