Background and Aim : Consanguinity is a deeply rooted social trend among one-fifth of the world population mostly residing in the developing countries/ with Asian and African descend. Consanguineous marriages are associated with an increased risk for congenital malformations and autosomal recessive diseases. Promoting advanced molecular biology technologies and the public awareness on prevention of congenital and genetic disorders in offspring promises better management of this condition Whole-exome sequencing (WES) provides the possibility of genome-wide preconception carrier screening. Methods : eripheral blood samples were collected from the patients and their family members after obtaining written informed consent. Next generation Sequencing (NGS), Targeted panel sequencing and Whole Exome Sequencing (WES), was initially performed on the proband. Data were analyzed using specific bioinformatics tools and genomic DNA was analyzed by PCR and Sanger sequencing using specific primers encompassing the exon and intronic boundaries of the identified variants in genes. Results : One Iranian 3 year old boy product of consanguineous marriage, with no previous family history of genetic disorders, diagnosed with metabolic disorder (organic academia) was investigated in this study. Targeted panel sequencing was conducted to identify the causative mutation proband. DNA analysis assessed likely pathogenic mutation in Mut gene, c.1874A> C. This finding was in accordance with patients phenotype. The mutations segregated in the parents as expected. In the next pregnancy of family PND tests performed on CVS sample. Fetus was heterozygous for Mut:c.1874A> C. Unfortunately new born had sever breathing distress. WES test results on new born shows another homozygous pathogenic mutation in NPC2 gene related to Niemann-pick disease. Conclusion : Consanguinity is a deeply rooted social trend with more than 1 billion people of world. This present study reports 2 offspring with two different fetal genetic disorders in consanguine family. Whole exome sequencing provides a useful tool in carrier detection of inherited genetic disorders in consanguine couples. Comprehensive molecular genetic testing such as WES will accelerate and simplify genetic counselling and promote accurate and immediate prognostic information allowing families to benefit from risk assessment schemes for further conception and prevention of affected Childs birth. Consanguinity is a deeply rooted social trend with more than 1 billion people of world. This present study rep