Maliheh Alimardani - Medical Genetics Research Center, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical- Sciences, Mashhad, Iran۳. Student Resear
Reza Ebrahimzadeh-Vesal - Pardis Pathobiology and Genetics Laboratory, Mashhad, Iran
Mohammad Reza Abbaszadegan - Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran- Pardis Pathobiology and Genetics Laboratory, Mashhad, Iran- Immunology Research Center, Mashhad University of Medical Science

Backgrounds: Mitochondrial trifunctional protein (M-FTP) deficiency, as a rare metabolicdisorder, classified into three phenotypes including lethal phenotype which begins in theneonatal period. The M-FTP protein catalyzes the oxidation of long chain fatty and composed of۸ subunits such long-chain ۲,۳-enoyl-CoA hydratase (LCEH) and long-chain ۳-hydroxyacylCoA dehydrogenase (LCHAD). LCHAD deficiency inherited as an autosomal recessive trait andassociated with HADHA gene mutations (OMIM: ۶۰۰۸۹۰). These cause a clinical spectrum ofsymptoms such as progressive peripheral neuropathy, hypoketotic hypoglycemia, hepatopathy,cardiomyopathy, myopathy and pigmentary retinopathy.Materials and Methods: We report an Iranian girl with an initial diagnosis of LCHADdeficiency using tandem mass spectrometry (MS/MS) who unexpectedly died on the ۷۰th dayafter birth. The parents were first cousins, with one healthy son, and a history of two previousmiscarriages.Results: When an AR disorder occurs in a family without familial history, the whole exomesequencing (WES) is an option to identify the genetic causal mutation in the parents of deceasedchild and then further confirmed by Sanger sequencing. The mother, with sectoralheterochromia, had heterozygous missense mutation “c.۲۰۲۶C>T (p. Arg۶۷۶Cys)” mutations inthe HADHA gene, diagnosed by WES. According to ACMG guideline and several predictiontools, this mutation is known as likely pathogenic mutation. Furthermore, she had ۲ otherheterozygous missense mutations in CFTR and PLEKHG۲ genes. Then, these ۳ mutations wereexamined in her husband by Sanger sequencing and the heterozygosity for “c.۲۰۲۶C>T (p.Arg۶۷۶Cys)” mutations in the HADHA gene was detected.Conclusion: Due to the validation of carrier state for mutant alleles in both parents andpathogenicity of c.۲۰۲۶C>T mutation in HADHA gene, this is the cause of the disease indeceased affected child. Moreover, it is important to perform genetic counseling and prenataldiagnosis (PND) for next pregnancy to prevent the birth of another affected child.

LCHAD deficiency, Metabolic disorder, M-FTP deficiency, Genetics