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Mitochondrial encephalocardio-myopathy with early neonatal onset due to TMEM70 mutation
Tomáš Honzík, Markéta Tesařová, Johannes A Mayr, Hana Hansíková, Pavel Ješina, Olaf Bodamer, Johannes Koch, Martin Magner, Peter Freisinger, Martina Huemer, Olga Kostková, Rudy van Coster, Stanislav Kmoch, Josef Houštêk, Wolfgang Sperl, Jiří Zeman
Language English Country England, Great Britain
Document type Journal Article, Multicenter Study, Research Support, Non-U.S. Gov't
Grant support
NS9759
MZ0
CEP Register
Digital library NLK
Full text - Article
Source
NLK
ProQuest Central
from 1996-01-01 to 6 months ago
Health & Medicine (ProQuest)
from 1996-01-01 to 6 months ago
Family Health Database (ProQuest)
from 1996-01-01 to 6 months ago
- MeSH
- Phenotype MeSH
- Hyperammonemia enzymology genetics MeSH
- Hypospadias enzymology genetics MeSH
- Infant MeSH
- Cryptorchidism enzymology genetics MeSH
- Humans MeSH
- Membrane Proteins genetics MeSH
- Mitochondrial Encephalomyopathies enzymology genetics MeSH
- Mitochondrial Proteins genetics MeSH
- Mitochondrial Proton-Translocating ATPases deficiency MeSH
- Mutation MeSH
- Infant, Newborn MeSH
- Retrospective Studies MeSH
- Age of Onset MeSH
- Check Tag
- Infant MeSH
- Humans MeSH
- Male MeSH
- Infant, Newborn MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Multicenter Study MeSH
- Research Support, Non-U.S. Gov't MeSH
OBJECTIVE: Mitochondrial disturbances of energygenerating systems in childhood are a heterogeneous group of disorders. The aim of this multi-site survey was to characterise the natural course of a novel mitochondrial disease with ATP synthase deficiency and mutation in the TMEM70 gene. METHODS: Retrospective clinical data and metabolic profiles were collected and evaluated in 25 patients (14 boys, 11 girls) from seven European countries with a c.317-2A-->G mutation in the TMEM70 gene. RESULTS: Severe muscular hypotonia (in 92% of newborns), apnoic spells (92%), hypertrophic cardiomyopathy (HCMP; 76%) and profound lactic acidosis (lactate 5-36 mmol/l; 92%) with hyperammonaemia (100-520 micromol/l; 86%) were present from birth. Ten patients died within the first 6 weeks of life. Most patients surviving the neonatal period had persisting muscular hypotonia and developed psychomotor delay. HCMP was non-progressive and even disappeared in some children. Hypospadia was present in 54% of the boys and cryptorchidism in 67%. Increased excretion of lactate and 3-methylglutaconic acid (3-MGC) was observed in all patients. In four surviving patients, life-threatening hyperammonaemia occurred during childhood, triggered by acute gastroenteritis and prolonged fasting. CONCLUSIONS: ATP synthase deficiency with mutation in TMEM70 should be considered in the diagnosis and management of critically ill neonates with early neonatal onset of muscular hypotonia, HCMP and hypospadias in boys accompanied by lactic acidosis, hyperammonaemia and 3-MGC-uria. However, phenotype severity may vary significantly. The disease occurs frequently in the Roma population and molecular-genetic analysis of the TMEM70 gene is sufficient for diagnosis without need of muscle biopsy in affected children.
Children's Hospital Schwabing Technical University Munich Munich Germany
Department of Pediatrics Landeskrankenhaus Bregenz Bregenz Austria
Department of Pediatrics Paracelsus Medical University Salzburg Austria
Department of Pediatrics University Hospital Ghent Ghent Belgium
References provided by Crossref.org
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