Mitochondrial myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare autosomal recessive disorder of oxidative phosphorylation that was initially described in 1974. MLASA has been associated with mutations in the pseudouridylate synthase 1 (PUS1), YARS2, and MTATP6 genes. Here we present the case of a 39 year old man with MLASA due to a homozygous Persian founder mutation at mRNA position 656 in exon 3 of the PUS1 gene, which resulted in the substitution of tryptophan for arginine at position 116 of the protein.
The patient first manifested symptoms with difficulty ambulating long distances during childhood followed by progressive weakness and falls. After receiving a Moderna COVID vaccine booster, he developed progressive weakness in the right upper and lower extremities. His brother shared his diagnosis and had been receiving blood transfusions for 15 years, and their parents are both carriers. The patient has three daughters, two of whom are symptomatic. This case lends further support to the pathogenic role of missense mutations of PUS1 in producing the MLASA phenotype.