Clinical Symptoms and Laboratory Data in 75 Children with Neonatal Manifestation of Mitochondrial Disease: Proposed Diagnostic Algorithms
Authors:
T. Honzík; M. Tesařová; H. Hansíková; L. Wenchich; K. Veselá; P. Ješina; M. Magner; J. Zeman
Authors‘ workplace:
Klinika dětského a dorostového lékařství UK 1. LF a VFN, Praha
přednosta prof. MUDr. J. Zeman, DrSc.
Published in:
Čes-slov Pediat 2010; 65 (7-8): 422-431.
Category:
Original Papers
Overview
Mitochondrial disorders may manifest at any age. High energetic demands associated with postnatal adaptation to extrauterinne life result in frequent onset of mitochondrial disorders in nenates. The aim of this study is to analyse clinical and laboratory characteristics of mitochondrial disorders with neonatal onset. Further, we would like to propose algorithms for diagnostics of neonatal mitochondrial disorders.
Study group:
Mitochondrial disorder manifested in 75 neonates, who comprise 21% of mitochondrial desease patients diagnosed on biochemical and/or molecular genetic level at our department.
Results:
Within our study group, 36% of children were delivered prematurely, intrauterinal growth retardation was present in 40% of them and early postnatal hypotonia was observed in 95% of patients. Ventilation support was necessary in 66% of the newborns, feeding refusal and lethargy predominated in the rest of them. Hypertrophic cardiomyopathy was observed in 50% and neonatal seizures in 24% of newborns. Leigh syndrome was diagnosed in 11% of neonates. The prognosis was not favourable, one third of children died in the first three months of life. Biochemical analyses revealed lactic acidosis (93%), elevated excretion of the Krebs cycle intermediates (75%), and increased creatine kinase activity (28%). Hyperammonemia was present in 22% of the children. All newborns with Tmem70 protein deficiency exhibited higher excretion of 3-methylglutaconic acid in urine.
Conclusion:
Neonatal manifestation of mitochondrial disorders is not rare. Only the precise description of clinical signs and laboratory markers of the disease and knowledge of the most common mitochondrial defects with neonatal onset enables to diagnose the specific syndrome in the case of the child death. The diagnostic algorithm for a critically ill newborn with suspicion of mitochondrial energetic metabolism defect was prepared. This algorithm also enables to indicate direct enzymatic or mutation analysis, either with no need of muscle biopsy in some cases.
Key words:
mitochondrial disorders, neonatal onset, lactic acidosis, hypertrophic cardiomyopathy, diagnosis algorithm
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Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2010 Issue 7-8
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