A mutation in canine PPT1 causes early onset neuronal ceroid lipofuscinosis in a Dachshund.

The neuronal ceroid lipofuscinoses (NCLs) are lysosomal storage diseases characterized by progressive neurodegeneration and accumulation of autofluorescent storage granules. A 9-month-old Miniature Dachshund presented with NCL-like signs that included disorientation, ataxia, weakness, visual impairment, and behavioral changes. Neurons throughout the CNS contained autofluorescent lysosomal inclusions with granular osmiophilic deposit (GROD) ultrastructure characteristic of classical infantile NCL (INCL). Human INCL is an autosomal recessive disorder that results from mutations in PPT1, a gene that encodes the enzyme palmitoyl protein thioesterase 1 (PPT1; EC 3.1.22). Resequencing of PPT1 from the affected dog revealed that the dog was homozygous for a single nucleotide insertion in exon 8 (PPT1 c.736_737insC), upstream from the His289 active site. Brain tissue from this dog lacked PPT1 activity. The sire and dam of the propositus were heterozygous for the c.736_737insC mutation; whereas, 127 unrelated Dachshunds were homozygous for the wild-type allele. This is the first reported instance of canine NCL caused by a mutation in PPT1.

In vitro evaluation of the efficacy of a veterinary dry heat fluid warmer.

OBJECTIVES: To evaluate the efficacy of a veterinary dry heat fluid warmer on ambient and prewarmed crystalloid fluids and refrigerated packed red blood cells (pRBC). DESIGN: Prospective in vitro study. SETTING: University teaching hospital. ANIMALS: None. INTERVENTIONS: Ambient and prewarmed crystalloid fluids and refrigerated pRBC were delivered via a standard fluid administration set at various rates. A thermistor continuously monitored fluid outflow temperature with and without a dry heat veterinary fluid warmer (study device). RESULTS: The outflow temperature was significantly higher with the study device as compared to control conditions for all fluids and rates tested. The maximum outflow temperature of approximately 35°C (95°F) occurred when the study device was applied to either ambient or prewarmed crystalloid fluids at 50 mL/h. In the study device trials, the outflow temperature of ambient crystalloid fluids ranged from 35.1° to 27.3°C (95.2° to 81.1°F) as the fluid rate increased from 50 to 999 mL/h. Control trials of prewarmed crystalloids produced outflow temperatures that rapidly approached ambient temperature. Addition of the study device to prewarmed crystalloids resulted in outflow temperatures that were similar to that of the corresponding ambient crystalloid trials. Control trials of refrigerated pRBC achieved ambient temperature at rates from 10 to 500 mL/h. With the study device, pRBC were maximally warmed to an outflow temperature of 35.8°C (96.4°F) at 100 mL/h. CONCLUSION: Although the study device generated statistically significant increases in outflow temperature of crystalloid fluids and pRBC, the ability of the device to decrease the metabolic cost of fluid administration is limited to specific clinical scenarios. The use of prewarmed crystalloid fluids with or without the study device offers minimal benefit over ambient temperature crystalloids. Substantial warming of pRBC occurs during administration, even without use of the study device.