Expanded inherited metabolic diseases screening by tandem mass spectrophotometry: The first report from Iran.

Inherited metabolic diseases (IMD) are a group of rare genetic disorders that can present with a variety of symptoms. Since these disorders are hard to treat once the symptoms occur, neonatal screening may be a logical strategy. Here we evaluate the first results of national expanded IMD screening in Iran. A total of 46 IMDs were screened in this national program. Between April 2018 and March 2022, all infants who underwent national IMD screening at Shahid Beheshti University of Medical Sciences were included in this study. History and Physical examinations of infants, screening results, recall rate, response rate, and prevalence of IMDs were evaluated. A total of 125,819 infants were screened during this period. The recall rate of the test was 0.81%. 124 cases were diagnosed with a definite IMD and the raw overall prevalence of IMDs was estimated to be 1:1015. Aminoacidopathies were the most commonly detected disorders and Hyperphenylalaninemia/PKU was the most prevalent disorder among all groups. Since IMDs vary from region even in a single country, screening for IMDs is crucial in societies with a high rate of consanguineous marriages. More studies are essential for figuring out the most efficient combination of diseases to be screened based on countries' facilities.

Identification of Novel Mutations in the MMAA and MUT Genes among Methylmalonic Aciduria Families.

Background: Methylmalonic aciduria is a rare inherited metabolic disorder with autosomal recessive inheritance pattern. There are still MMA patients without known mutations in the responsible genes. This study aimed to identify mutations in Iranian MMA families using autozygosity mapping and NGS. Methods: Multiplex PCR was performed on DNAs isolated from 12 unrelated MMA patients and their family members using 19 STR markers flanking MUT, MMAA, and MMAB genes, followed by Sanger sequencing. WES was carried out in the patients with no mutation. Results: Haplotype analysis and Sanger sequencing revealed two novel, mutations, A252Vf*5 and G87R, within the MMAA and MUT genes, respectively. Three patients showed no mutations in either autozygosity mapping or NGS analysis. Conclusion: High-frequency mutations within exons 2 and 3 of MUT gene and exon 7 of MMAB gene are consistent with the global expected frequency of genetic variations among MMA patients.