title: Fetal left ventricular noncompaction cardiomyopathy and fatal outcome due to complete deficiency of mitochondrial trifunctional protein.
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 Intensive care was withdrawn due to failure to thrive and suspicion of a severe mitochondrial disorder.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.
  
  
  CONCLUSIONS
  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.
  
  
  BACKGROUND
  • Mitochondrial disorders as a group are an important etiology for fetal cardiomyopathies including human trifunctional protein (TFP) disorders and several other mitochondrial diseases.
  
  
  BACKGROUND
  • We report a fetal case with fatal outcome having a novel mitochondrial trifunctional protein mutation (c.1109+243_1438-703del in the HADHB gene).
authors.affiliation: Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. tiina.h.ojala@hus.fi.
authors.forename: Tiina
authors.initials: T
authors.lastname: Ojala
authors.affiliation: Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. irmeli.nupponen@hus.fi.
authors.forename: Irmeli
authors.initials: I
authors.lastname: Nupponen
authors.affiliation: Department of Clinical Genetics, Finland and Fetomaternal Center, Helsinki University Hospital, Helsinki, Finland. carola.saloranta@hus.fi.
authors.forename: Carola
authors.initials: C
authors.lastname: Saloranta
authors.affiliation: Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. taisto.sarkola@hus.fi.
authors.forename: Taisto
authors.initials: T
authors.lastname: Sarkola
authors.affiliation: Department of Pediatric Cardiology, The John Hopkins Hospital, Baltimore, MD, USA. psekar1@jhmi.edu.
authors.forename: Priya
authors.initials: P
authors.lastname: Sekar
authors.affiliation: Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. anniina.breilin@fimnet.fi.
authors.forename: Anniina
authors.initials: A
authors.lastname: Breilin
authors.affiliation: Department on Pediatrics, Children's Hospital, University Hospital of Helsinki, Stenbackinkatu 11, PL 281, 00029 HUS, Helsinki, Finland. tiina.tyni@helsinki.fi.
authors.forename: Tiina
authors.initials: T
authors.lastname: Tyni
mesh_terms: D000328:Adult; D009202:Cardiomyopathies / Q000175:diagnosis / Q000235:genetics*; D004452:Echocardiography; D017809:Fatal Outcome; D005260:Female; D005315:Fetal Diseases; D005333:Fetus; D006352:Heart Ventricles / Q000002:abnormalities*; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors / Q000175:diagnosis / Q000235:genetics*; D017240:Mitochondrial Myopathies / Q000175:diagnosis / Q000235:genetics*; D063991:Mitochondrial Trifunctional Protein / Q000172:deficiency* / Q000235:genetics; D063993:Mitochondrial Trifunctional Protein, beta Subunit / Q000235:genetics*; D009154:Mutation; D009422:Nervous System Diseases / Q000175:diagnosis / Q000235:genetics*; D011247:Pregnancy; D012206:Rhabdomyolysis / Q000175:diagnosis / Q000235:genetics*
chemical_list: C576206:HADHB protein, human; D063991:Mitochondrial Trifunctional Protein; D063993:Mitochondrial Trifunctional Protein, beta Subunit
keywords: Echocardiography; Fetal cardiomyopathy; Noncompaction cardiomyopathy; Trifunctional protein