Erythrocytic pyruvate kinase mutations causing hemolytic anemia, osteosclerosis, and secondary hemochromatosis in dogs.

BACKGROUND: Erythrocytic pyruvate kinase (PK) deficiency, first documented in Basenjis, is the most common inherited erythroenzymopathy in dogs. OBJECTIVES: To report 3 new breed-specific PK-LR gene mutations and a retrospective survey of PK mutations in as mall and selected group of Beagles and West Highland White Terriers (WHWT). ANIMALS: Labrador Retrievers (2 siblings, 5 unrelated), Pugs (2 siblings, 1 unrelated), Beagles (39 anemic, 29 other),WHWTs (22 anemic, 226 nonanemic), Cairn Terrier (n = 1). METHODS: Exons of the PK-LR gene were sequenced from genomic DNA of young dogs (<2 years) with persistent highly regenerative hemolytic anemia. RESULTS: A nonsense mutation (c.799C>T) resulting in a premature stop codon was identified in anemic Labrador Retriever siblings that had osteosclerosis, high serum ferritin concentrations, and severe hepatic secondary hemochromatosis. Anemic Pug and Beagle revealed 2 different missense mutations (c.848T>C, c.994G>A, respectively) resulting in intolerable amino acid changes to protein structure and enzyme function. Breed-specific mutation tests were developed. Among the biased group of 248 WHWTs, 9% and 35% were homozygous (affected) and heterozygous, respectively, for the previously described mutation (mutant allele frequency 0.26). A PK-deficient Cairn Terrier had the same insertion mutation as the affected WHWTs. Of the selected group of 68 Beagles, 35% were PK-deficient and 3% were carriers (0.37). CONCLUSIONS AND CLINICAL IMPORTANCE: Erythrocytic PK deficiency is caused by different mutations in different dog breeds and causes chronic severe hemolytic anemia, hemosiderosis, and secondary hemochromatosis because of chronic hemolysis and, an as yet unexplained osteosclerosis. The newly developed breed-specific mutation assays simplify the diagnosis of PK deficiency.

Somatosensory evoked potential monitoring in anterior thoracic vertebrectomy.

OBJECT: Spine surgeons have used intraoperative cortical and subcortical somatosensory evoked potential (SSEP) monitoring to detect changes in spinal cord function when intraoperative procedures can be performed to prevent neurological deterioration. However, the reliability of SSEP monitoring as applied to anterior thoracic vertebral body resections has not been rigorously assessed. METHODS: The authors retrospectively reviewed hospital charts and operating room records obtained between August 1993 and December 1998 and found that SSEP monitoring was used in 44 surgical procedures involving an anterior approach for thoracic vertebral body resections. There were no patients in whom SSEP changes did not return to baseline during the surgical procedure. Patients in four cases, despite their stable SSEP recordings throughout the procedure, were noted immediately postoperatively to have experienced significant neurological deterioration. The false-negative rate in SSEP monitoring was 9%. Sensitivity was determined to be 0%. CONCLUSIONS: It is important to recognize high false-negative rates and low sensitivity of SSEP monitoring when it is used to record spinal cord function during anterior approaches for thoracic vertebrectomies. The insensitivity of SSEPs for motor deterioration during anterior thoracic vertebrectomies is likely due to the limitation of SSEPs, which monitor only posterior column function whereas motor paths are conveyed in the anterior and anterolateral spinal cord. The authors believe that SSEPs can not be relied on to detect reversible spinal damage during anterior thoracic vertebrectomies.