Niacin supplementation in a child with novel MTTN variant m.5670A>G causing early onset mitochondrial myopathy and NAD+ deficiency.
Neuromuscul Disord
; 43: 14-19, 2024 Aug 02.
Article
in En
| MEDLINE
| ID: mdl-39173541
ABSTRACT
Myopathy is a common manifestation in mitochondrial disorders, but the pathomechanisms are still insufficiently studied in children. Here, we report a severe, progressive mitochondrial myopathy in a four-year-old child, who died at eight years. He developed progressive loss of muscle strength with nocturnal hypoventilation and dilated cardiomyopathy. Skeletal muscle showed ragged red fibers and severe combined respiratory chain deficiency. Mitochondrial DNA sequencing revealed a novel m.5670A>G mutation in mitochondrial tRNAAsn (MTTN) with 88 % heteroplasmy in muscle. The proband also had systemic NAD+ deficiency but rescuing this with the NAD+ precursor niacin did not stop disease progression. Targeted metabolomics revealed an overall shift of metabolism towards controls after niacin supplementation, with normalized tryptophan metabolites and lipid-metabolic markers, but most amino acids did not respond to niacin therapy. To conclude, we report a new MTTN mutation, secondary NAD+ deficiency in childhood-onset mitochondrial myopathy with metabolic but meager clinical response to niacin supplementation.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Language:
En
Journal:
Neuromuscul Disord
Journal subject:
NEUROLOGIA
Year:
2024
Document type:
Article
Publication country:
ENGLAND
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ESCOCIA
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GB
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GREAT BRITAIN
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INGLATERRA
/
REINO UNIDO
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SCOTLAND
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UK
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UNITED KINGDOM