Severe linezolid-induced lactic acidosis in a child with acute lymphoblastic leukemia: A case report.

Linezolid is an antibiotic increasingly used for treatment of resistant Gram-positive infections, which blocks bacterial proteosythesis through direct inhibition of mitochondrial ribosomes. The most common adverse effects of linezolid include gastrointestinal symtoms, peripheral neuropathy, bone marrow depression and lactic acidosis. Here we present a rare case of a 9-year-old female, a survivor of acute lymphoblastic leukemia (ALL) and a hematopoietic stem cell transplant (HSCT), who developed life-threatening lactic acidosis with vomiting, impaired consciousness and Kussmaul breathing after 51 days of intravenous linezolid administration due to mycobacterial infection. She fully recovered after drug discontinuation and normalization of the plasma levels. We conclude that plasma lactate concentrations should be monitored closely during any linezolid treatment, particularly in patients with hepatic or renal dysfunction.

The Czech National Diamond-Blackfan Anemia Registry: clinical data and ribosomal protein mutations update.

Diamond-Blackfan anemia is a rare inherited bone marrow failure syndrome diagnosed in early infancy that is characterized by a (a) macrocytic anemia with no other significant cytopenia, (b) reticulocytopenia, and (c) normal bone marrow cellularity with a paucity of erythroid precursors. Physical anomalies are often present. Mutations in several ribosomal proteins have been associated with the disease. Here we present a detailed description of 39 patients from 34 families enrolled in the Czech National Diamond-Blackfan Anemia Registry. Erythrocyte adenosine deaminase activity and serum erythropoietin levels were measured and bone marrow analysis and clonogenic assays were carried out. Twenty-two different ribosomal proteins were sequenced. We identified mutations in five different ribosomal proteins in 28/39 patients (71.8%) from 23/34 families (67.6%). Several new mutations are described. The most interesting data relate to genotype-phenotype correlations. All patients with ribosomal protein L5 or ribosomal protein L11 mutations have a thumb defect usually with one or more other anomalies. Most of these patients were born small for gestational age and currently have short stature. We also described five patients with a ribosomal protein S26 mutation. All of the latter are transfusion-dependent and they exhibit skeletal abnormalities rather than thumb or craniofacial deformities. Patients with ribosomal protein S19 seem to bear mildest associated anomalies, usually in a craniofacial region.