Abstract
We report a fetal case with fatal outcome having a novel mutation in the HADHB gene, coding the beta-subunit of the mitochondrial trifunctional protein. Parents had a previous pregnancy loss due to fetal heart failure and hydrops. The next pregnancy led to left ventricular noncompaction and increasing pleural effusions after 29 gestational weeks. The fetus was small for gestational age, and long bones were abnormally short. The baby was born severely asphyxiated at 32 gestational weeks by cesarean section. Intensive care was withdrawn due to failure to thrive and suspicion of a severe mitochondrial disorder. Postmortem brain MRI suggested microcephaly with a simplified gyral pattern. The lateral cerebral ventricles were normal. Chromosome analysis was normal (46, XX). Fibroblasts cultured from a skin biopsy of the baby revealed the large homozygous deletion c.1109+243_1438-703del in the HADHB gene, and heterozygous mutations were detected in both parents. The deletion has not been reported earlier.
Conclusion: It is important to differentiate systemic metabolic diseases from disorders that affect only the cardiac muscle. Trifunctional protein deficiency is a relatively rare disorder of the fatty acid β-oxidation cycle. The mutation in the HADHB gene causes a systemic disease with early-onset cardiomyopathy. Understanding the molecular genetic defect of the patient allows appropriate genetic counseling of the family.
What is Known: • Mitochondrial disorders as a group are an important etiology for fetal cardiomyopathies including human trifunctional protein (TFP) disorders and several other mitochondrial diseases. |
What is New: • We report a fetal case with fatal outcome having a novel mitochondrial trifunctional protein mutation (c.1109+243_1438-703del in the HADHB gene). |
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Abbreviations
- AFLP syndrome:
-
Acute fatty liver pregnancy syndrome
- HADHA gene:
-
Gene encoding the α-subunit of long-chain hydroxyacyl-CoA dehydrogenase
- HADHB gene:
-
Gene encoding the β-subunit of long-chain hydroxyacyl-CoA dehydrogenase
- HELLP syndrome:
-
Hemolysis, elevated liver enzyme, low platelet syndrome
- TFP:
-
Trifunctional protein
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Acknowledgments
The manuscript was supported by grants from the Finnish Pediatric Research Foundation.
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The authors declare that they have no competing interests.
Compliance with ethical standards
All procedures performed in study involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. Written informed consent was obtained from the parents.
Authors Contributions
Dr Tiina Ojala and Tiina Tyni are primary responsibility for data collection and data analysis and writing the manuscript.
Dr Tiina Ojala, Tiina Tyni, Taisto Sarkola, Irmeli Nupponen and Carola Saloranta contributed to the clinical treatment of the patients and the writing of the manuscript.
Dr Priya Sekar and Dr Anniina Breilin contributed to the interpretation of the analysis and writing of the manuscript.
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Communicated by Mario Bianchetti
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Ojala, T., Nupponen, I., Saloranta, C. et al. Fetal left ventricular noncompaction cardiomyopathy and fatal outcome due to complete deficiency of mitochondrial trifunctional protein. Eur J Pediatr 174, 1689–1692 (2015). https://doi.org/10.1007/s00431-015-2574-9
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DOI: https://doi.org/10.1007/s00431-015-2574-9