Review Propionic acidemia in the Arab World Hatem Zayed Department of Health Sciences, Biomedical Program, Qatar University, Doha, Qatar abstract article info Article history: Received 18 December 2014 Received in revised form 29 March 2015 Accepted 7 April 2015 Available online 9 April 2015 Keywords: Propionic acidemia PCCA PCCB Arabs Genotype–phenotype correlation Mutations The autosomal recessive disease propionic acidemia (PA) is an inborn error of metabolism with highly variable clinical manifestations, caused by a deficiency of propionyl-CoA carboxylase (PCC) enzyme, due to mutations in either PCCA or PCCB genes, which encode the alpha and beta subunits of the PCC enzyme, respectively. The clas- sical clinical presentation consists of poor feeding, vomiting, metabolic acidosis, hyperammonemia, lethargy, neurological problems, and developmental delay. PA seems to be a prevalent disease in the Arab World. Arab pa- tients with PA seem to have the same classical clinical picture for PA with distinctive associated complications and other diseases. Most of the mutations found in Arab patients seem to be specific to the Arab population, and not observed in other ethnic groups. In this review, I will discuss in details the clinical and molecular profile of Arab patients with PA. © 2015 Elsevier B.V. All rights reserved. Contents 1. Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 2. Genotype–phenotype correlation in non-Arab PA patients belong to diverse ethnic groups . . . . . . . . . . . . . . . . . . . . . . . . . . 120 2.1. Strong genotype–phenotype correlation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 2.2. Inconclusive genotype–phenotype correlation . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 120 3. PA in Arabia . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 4. Clinical profile of Arab patients with PA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 121 5. Molecular studies in Arab patients with PA . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 122 6. Future directions and conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 123 1. Introduction Propionic acidemia (PA; MIM# 232000 and 232050) is an autosomal recessive inherited inborn error of metabolism. It is caused by a defi- ciency of the mitochondrial enzyme propionyl-CoA carboxylase (PCC) enzyme (Hsia et al., 1971), which converts propionyl coenzyme A (pro- pionyl-CoA) to methylmalonyl-coenzyme A (methylmalonyl-CoA), leading to impaired metabolism of branched-chain amino acids, such as isoleucine and valine, methionine, threonine, cholesterol side chains, odd numbered fatty acids, thymine and uracil. PCC enzyme is a dodecamer comprised of alpha and beta subunits; the alpha subunit is encoded by the PCCA gene (chromosome 13q32, MIM#232000; NCBI Reference Sequence: NG_008768.1). The beta subunit is encoded by the PCCB gene (chromosome 3q13.3–q22, MIM#232050; NCBI Refer- ence Sequence: NG_008939.1) (Lamhonwah et al., 1986). Mutations in either the PCCA or PCCB gene cause PCC enzyme deficiency. To date, the Human Gene Mutation Database (http://www.hgmd. org) has reported 98 mutations in PCCA gene and 98 mutations in PCCB gene. According to the Exome variant service (EVS), 183 variants have been reported for the PCCA gene and 133 in the PCCB gene. The ma- jority of these mutations were missense mutation (40%) (http://cbs.lf1. Gene 564 (2015) 119–124 Abbreviations: PA, propionic acidemia; IEMs, inborn errors of metabolism; PCC, propionyl-CoA carboxylase; PCCA, propionyl-CoA carboxylase, alpha subunit; PCCB, propionyl-CoA carboxylase, beta subunit. E-mail address: hatem.zayed@qu.edu.qa. http://dx.doi.org/10.1016/j.gene.2015.04.019 0378-1119/© 2015 Elsevier B.V. All rights reserved. Contents lists available at ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene