Abstract
Defects in the human gene encoding methylmalonyl-CoA mutase enzyme (MCM) give rise to a rare autosomal recessive inherited disorder of propionate metabolism termed mut methylmalonic acidemia (MMA). Patients with mut MMA have been divided into two subgroups: mut(0) with complete loss of MCM activity and mut-with residual activity in the presence of adenosylcobalamin (AdoCbl). The disease typically presents in the first weeks or months of life and is clinically characterized by recurrent vomiting, metabolic acidosis, hyperammonemia, lethargy, poor feeding, failure to thrive and neurological deficit. To better elucidate the spectrum of mutations causing mut MMA in Saudi patients, we screened a cohort of 60 Saudi patients affected by either forms of the disease for mutations in the MUT gene. A total of 13 different mutations, including seven previously reported missense changes and six novel mutations, were detected in a homozygous state except for two compound heterozygous cases. The six novel mutations identified herein consist of three nonsense, two missense and one frameshift, distributed throughout the whole protein. This study describes for the first time the clinical and mutational spectrum of mut MMA in Saudi Arabian patients.