Tiina Ojala1, Irmeli Nupponen2, Carola Saloranta3, Taisto Sarkola4, Priya Sekar5, Anniina Breilin6, Tiina Tyni7. 1. Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. tiina.h.ojala@hus.fi. 2. Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. irmeli.nupponen@hus.fi. 3. Department of Clinical Genetics, Finland and Fetomaternal Center, Helsinki University Hospital, Helsinki, Finland. carola.saloranta@hus.fi. 4. Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. taisto.sarkola@hus.fi. 5. Department of Pediatric Cardiology, The John Hopkins Hospital, Baltimore, MD, USA. psekar1@jhmi.edu. 6. Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. anniina.breilin@fimnet.fi. 7. Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. tiina.tyni@helsinki.fi.
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 Intensive care was withdrawn due to failure to thrive and suspicion of a severe mitochondrial disorder.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).
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).
Entities:
Keywords:
Echocardiography; Fetal cardiomyopathy; Noncompaction cardiomyopathy; Trifunctional protein
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