A Novel PUS1 Mutation in 2 Siblings with MLASA Syndrome: A Review of the Literature.

ABSTRACT: Myopathy, lactic acidosis, and sideroblastic anemia (MLASA) is a rare mitochondrial disorder characterized by MLASA. Variable features of this condition include failure to thrive, and developmental delay or intellectual disability. Additional symptoms consist of cognitive impairment, skeletal and dental abnormalities, delayed motor milestones, cardiomyopathy, dysphagia, and respiratory insufficiency. MLASA has previously been associated with mutations in pseudouridylate synthase 1 (PUS1) and YARS2. PUS1 encodes the nuclear PUS1 enzyme, which is located in both the nucleus and the mitochondria. PUS1 converts uridine into pseudouridine in several cytosolic and mitochondrial transfer RNA positions and increases the efficiency of protein synthesis in both compartments.In the present report, we report on 2 Turkish sisters 4 and 11 of years with an MLASA plus phenotype. Both patients have sideroblastic anemia, lactic acidosis, failure to thrive, developmental delay, and chronic diarrhea; in addition, the older sister has strabismus and skeletal anomalies. The sequencing of the PUS1 gene revealed a novel homozygous p.Glu311* mutation. The phenotype of the older sibling is also unique because of the strabismus and skeletal anomalies, when compared with her sister and other previously reported patients with MLASA. The structural differences in the nuclear versus mitochondrial isoforms of PUS1 and modifier genes may be implicated in the variability of the clinical presentations in MLASA. CONCLUSION: This report adds to the growing number of mutations causing complex clinical manifestations of MLASA including lactic acidosis, sideroblastic anemia, chronic diarrhea, and myopathy.

Severe theophylline poisoning treated with continuous venovenous hemodialysis in a child.

Theophylline poisoning generally occurs due to acute high dose intake as well as chronic intake of the medication. Toxicity symptoms can be seen with a plasma concentration of theophylline over 20 µg/ml. The consequences of theophylline toxicity include metabolic disturbances (hypokalemia, hyperglycemia, and metabolic acidosis), nausea, vomiting, and in severe cases seizures, cardiac arrhythmias, and death. Theophylline poisoning in children is rarely described in the literature. A 3-year-old girl was referred from another hospital to our pediatric intensive care unit (PICU) due to prolonged refractory status epilepticus and respiratory failure linked with severe theophylline poisoning. The patient was admitted to our PICU 24 hours after the patient took theophylline. The referring center could not measure the serum theophylline level. The patient's first serum theophylline level that was checked at admission was 54 µg/ml. We started continuous venovenous hemodialysis (CVVHD) 3 hours after PICU admission and the patient's theophylline level successfully decreased within 9 hours. The patient was discharged at the 40th day of admission from our hospital with severe neurological disability. In conclusion, severe theophylline poisoning may be seen in children. We must consider CVVHD in critically ill children with severe theophylline poisoning.