The spectrum of peripheral neuropathy in disorders of the mitochondrial trifunctional protein
| Autor: | Sarah C. Grünert, Ute Spiekerkoetter, Martin Lindner, Matthias Eckenweiler, Dorothea Haas, René Santer, Sara Tucci, Konstantinos Tsiakas |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male medicine.medical_specialty Adolescent Fulminant Mitochondrial trifunctional protein deficiency Mitochondrial trifunctional protein Early initiation Gastroenterology Lipid Metabolism Inborn Errors Rhabdomyolysis Young Adult 03 medical and health sciences Internal medicine Genetics medicine Humans Child Genetics (clinical) 030304 developmental biology 0303 health sciences Newborn screening biology Mitochondrial Trifunctional Protein business.industry 030305 genetics & heredity Age Factors Infant Newborn Infant Mitochondrial Myopathies Peripheral Nervous System Diseases medicine.disease Pathophysiology Phenotype Peripheral neuropathy Child Preschool biology.protein Female Nervous System Diseases Cardiomyopathies Complication business |
| Zdroj: | Journal of Inherited Metabolic Disease. 44:893-902 |
| ISSN: | 1573-2665 0141-8955 |
| DOI: | 10.1002/jimd.12372 |
| Popis: | Peripheral neuropathy is a known irreversible long-term complication of long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHADD) and mitochondrial trifunctional protein deficiency (MTPD), two inherited disorders of mitochondrial long-chain fatty acid oxidation. The underlying pathophysiology of neuropathy is still not fully understood. We report electrophysiological studies and neurological findings in a series of 8 LCHAD-deficient and 11 MTP-deficient patients. The median age at time of the study was 8.0 years (0.5-25 years). The overall prevalence of neuropathy was 58% with neuropathic symptoms being slightly more common in MTPD compared to LCHADD (70% vs 50%, respectively). Onset of neuropathy was significantly earlier in MTPD patients compared to LCHADD patients (median age at onset 4.7 vs 15.3 years, respectively, P = .047). In four patients, isolated peripheral neuropathy was the first and only presenting symptom, and in all four the diagnosis was missed by newborn screening. About half of the patients (45.5%) had a sensorimotor neuropathy, while 27.3% showed a pure motor form and another 27.3% an isolated sensory form. Despite early diagnosis by newborn screening and early initiation of therapy, peripheral neuropathy cannot be prevented in all patients with LCHADD/MTPD and has severe impact on the life of affected patients. Electrophysiology classifies LCHADD/MTPD neuropathy as axonal with secondary demyelination. A novel observation is that in patients with acute, fulminant onset of neuropathy, symptoms can be partly reversible. Further studies are needed to elucidate the underlying pathophysiology of axonal damage and possible therapeutic targets. |
| Databáze: | OpenAIRE |
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