The spectrum of peripheral neuropathy in disorders of the mitochondrial trifunctional protein.
Adolescent
Adult
Age Factors
Cardiomyopathies
/ complications
Child
Child, Preschool
Female
Humans
Infant
Infant, Newborn
Lipid Metabolism, Inborn Errors
/ complications
Male
Mitochondrial Myopathies
/ complications
Mitochondrial Trifunctional Protein
/ deficiency
Nervous System Diseases
/ complications
Peripheral Nervous System Diseases
/ diagnosis
Phenotype
Rhabdomyolysis
/ complications
Young Adult
LCHAD
MTP
complication
fatty acid oxidation
long chain 3-hydroxyacyl-CoA dehydrogenase deficiency
mTFP
mitochondrial trifunctional protein deficiency
neuropathy
Journal
Journal of inherited metabolic disease
ISSN: 1573-2665
Titre abrégé: J Inherit Metab Dis
Pays: United States
ID NLM: 7910918
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
25
02
2021
received:
15
12
2020
accepted:
25
02
2021
pubmed:
28
2
2021
medline:
18
1
2022
entrez:
27
2
2021
Statut:
ppublish
Résumé
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.
Substances chimiques
Mitochondrial Trifunctional Protein
EC 2.3.1.16
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
893-902Informations de copyright
© 2021 The Authors. Journal of Inherited Metabolic Disease published by John Wiley & Sons Ltd on behalf of SSIEM.
Références
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