Glycogen Branching Enzyme Deficiency in a foal

History: A 1 week-old male Quaterhorse was submitted for necropsy. At 12 hours old he nursed 3 times but became progressively recumbent and failed to nurse. Upon arrival to the referral hospital he was laterally recumbent with poor mentation. Initial blood chemistry revealed blood glucose of 93 mg/dL, BUN 27 mg/dL, Creatinine of 4.3 mg/dL, lactate of 2.2 mmol/L, CK > 30,000 u/L, and hypoproteinemia. Muscle biopsies were sent to the University of Minnesota. CBC indicated left shift. Later CBC/Chem indicated leukopenia, anemia, hypoproteinemia, hyperfibrinogenemia, and hyperglycemia. He died acutely.

Gross Findings:

The foal was thin with minimal body fat stores. The cranial lung lobes were bilaterally dark red, and firm. There was mild interlobular edema and collapse of the cranial lung lobes. The trachea, primary bronchi, and itra-lobular bronchi contained serous and fibrinous exudate.

The skeletal muscles were diffusely soft pale and pink.

Histopathology:

Skeletal muscle: There is mild multifocal myocyte degeneration and necrosis. Diffusely large numbers of myocyes contain intracytoplasmic pale basophilic round inclusions which replace the sarcoplasm. Myocytes also have pale vacuoles in the cytoplasm.

Heart: Cardiac myocytes are similar to skeletal muscle. The most striking feature is the large basophilic inclusions in Purkinje fibers.

Heart, Skeletal muscle PAS w/ glycogen digestion: Both the pale basophilic inclusions and the pale vacuolar areas in the cytoplasm are positive with PAS/with glycogen digestion (using diastase or amylase).

Heart, H&E stain: Cardiac myocytes contain pale basophilic inclusions and often have pale vacuolated areas

Heart, PAS/Amylase: PAS positive material (dark purple) is found as clumps of granular subtance in myocytes, and as smooth round inclusions. This is not digested with amylase indicating its not normal glycogen, rather some abnormal polysaccharide

Hear, H&E stain: IN the center the Purkinje fibers contain large pale basophilic inclusions

Heart, PAS/amylase: Amylase resistant polysaccharide bodies coincides with the pale basophilic inclusions, and the pale vacuolar areas

Normal Heart, PAS/amylase: Normal glycogen is digested by amylase and is not present in normal heart from a control animal

Normal Muslce, PAS/amylase: Normal glycogen is digested by amylase leaving no PAS positive material in cells

Morphologic Diagnosis:

Skeletal muscle: Generalized multifocal myocyte necrosis, with diffuse pale basophilic amylase resistant sarcoplasmic inclusions, and amylase resistant polysaccharide.

Heart: Diffuse cardiomyocyte and Purkinje fiber inclusions and amylase resistant polysaccharide.

Comment:

Glycogen Branching Enzyme Deficiency is an inherited defect in an enzyme that creates branches in glycogen for storage in tissues.  This disease is similar to the Type IV glycogenosis in humans (glycogen storage disease caused by a deficiency in alpha-1,4-glucan 6-glycosyl transferase). It is also similar to adult polyglucosan body disease in humans, also caused by a defect in a glycogen branching enzyme.  Organs affected with these disease include liver, CNS, PNS, and muscles.  The defect is an inherited autosomal recessive mutation in the GBE1 gene, causing a premature stop codon. This mutation results in poorly functional enzyme and therefore poorly branched glycogen, which is not capable of being transformed into glucose by debranching enzyme.

The University of California Davis and Vetgen are  licensed  to conduct testing to test a foal, mare or stallion for carrier status.  You can find more information at www.vgl.ucdavis.edu and www.vetgen.com.

References:

Ward, T.L. et al. 2004. Glycogen branching enzyme (GBE1) mutation causing equine glycogen storage disease IV. Mammalian Genome vol 15: 570-577.

Valberg, S.J. et al. 2001. Glycogen Branching Enzyme Deficiency in Quarter Horse Foals. J. Vet. Intern. Med. Vol 15:572-580.

Canine Adenovirus Pneumonia in 2 puppies- CAV-2

History: Two English Bulldog puppies (1, and 3 weeks old) had trouble breathing in the morning and by noon had died.

Gross Necropsy Findings:

Lungs: Diffuse dark red to purple, edematous.

Histologic Findings:

Lung: At low power, centered around bronchioles and extending into the interstitium are cellular infiltrates. Bronchiolar epithelium is sloughing off the basement membranes

Lung: At higher power, centered on a bronchiole there is necrosis and sloughing of respiratory epithelium. Epithelia contain nuclear inclusions which fill the nucleus or marginate the chromatin (arrow)

Lung, bronchiole at high power: Intranuclear inclusions are visible, and the lumen of the bronchiole contains necrotic cell debris and degenerate neutrophils, indicating a bacterial component secondary to loss of epithelial defenses.

Lungs, alveolar spaces: The lung is collapsed, alveolar capillaries are congested, and there is necrosis of type 1 pneumocytes, and intranuclear inclusions. There are a few neutrophils present.

Lungs: Multifocal necrosis of bronchiolar respiratory epithelium and alveolar pneumocytes. Alveolar septa are expanded by moderate numbers of macrophages, lymphocytes, plasma cells, and neutrophils (degenerate and intact). Respiratory epithelia contain large basophilic intra-nucelar viral inclusions that displace the chromatin. There is diffuse vascular congestion.

Liver: There are multifocal areas of hepatocellular necrosis with small numbers of macrophages. There are small numbers of macrophages in the portal areas. There is diffuse vascular congestion.

Morphologic Diagnosis: 

Lungs: Multifocal to coalescing broncho-interstitial pneumonia, necrotizing, lymphoplasmacytic and neutrophilic, severe, with intraepithelial intra-nuclear viral inclusions.

Liver:  Multifocal, random, hepatic necrosis, moderate

Bacterial cultures: Small numbers of  non-hemolytic E coli were cultured from the lungs and liver, and small numbers of Klebsiella spp were cultured from the lungs.

Comment:

The features of the pneumonia are diagnostic for Canine Adenovirus type 2.  This disease affects unvaccinated juvenile dogs and is distinct from disease caused by Canine Adenovirus type 1 (Infectious Canine Hepatitis).  Infections may be mild particularly in vaccinated animals, and limited to the upper respiratory tract, producing a serous or catarrhal rhinitis or tracheitis.  Disease in the lungs is severe when complicated by bacterial pneumonia.  In this case the disease was peracute, the lesions are necrosis with only moderate cellular infiltrates, and no type 2 pneumocyte hyperplasia which takes at least 3-4 days to appear. Bacterial cultures indicate a possible complication with bacterial pneumonia. Common bacterial causes of pneumonia in dogs do include E coli, particularly in newborn pups, as well as Klebsiella pneumoniae, Bordetella bronchiseptica, Pasteurella spp, and Streptococcus spp.  Multifocal hepatic necrosis indicates bacterial sepsis and likely contributed to the acute death in these pups.

Reference:

Lopez, Alfonso. Respiratory System, Chapter 9 in Pathologic Basis of Veterinary Disease 4th edition, McGavin, M.D., and Zachary, J.F. editors. 2004 Mosby Elsevier.

Salmonellosis in a Boa constrictor

History: A 3-year-old female Boa constrictor has no prior clinical signs.

Gross findings: The snake was in good body condition. The ventral scales were multifocally reddened, and the gingiva of the upper jaw was reddened.  The gall bladder was moderately distened with bile, and the bile duct was not patent.

The duodenum distal to the bile duct was dilated, and the serosal surface was dark red to black.  The mucosa was hyperplastic, and necrotic.

The liver contained multifocal tan foci from 1-3 mm throughout the organ.

The pericardium contained 7 ml of clear serous fluid.

Gall Bladder and intestine: The gall bladder is swollen with edema involving the wall and serosal layers

Gall Bladder and Small intesine: The intestinal mucosa is proliferative, appearing as many small fronds (shag carpet)

Small Intestine: When completely opened up the proliferative mucosa extends about 5 cm distally and is circumferential in distribution. The adjacent mucosa to the right is normal.

Histopathology:

Duodenum:  The mucosa was hyperplastic and covered by a thick mat of fibrin, necrotic cellular debris (diphtheritic membrane), mixed with serum and degenerate heterophils. There was bacterial overgrowth (post-mortem).

Small Intestine: The mucosa is hyperplastic, thickened. There is necrosis of the mucosa and submucosa which can be seen in the photo. There was a moderate degree of post-mortem autolysis which made interpretation of inflammatory cells difficult

Small Intestine mucosa: The mucosa is expanded by hemorrhage and fibrin

Liver: The liver was moderately autolyzed, but even so,there are discernable random multifocal areas of hepatocellular lytic necrosis.

Liver: There is a central zone of hepatocellular necrosis with cytoplasmic and nuclear cell debris

Heart: There is multifocal myocardiocyte degeneration and necrosis, and accumulation of large numbers of macrophages and fibroblast proliferation.

Heart: The myocardium is infiltrated by small numbers of heterophils and there is a small amount of karyorrhexis and sarcoplasmic fragmentation indicative of necrosis

Bacterial Culture: Salmonella group D1, and D2 was cultured from all tissues.

Comment:

Salmonellosis is a common cause of fibrino-necrotic enteritis, necrotizing hepatitis and septicemia in lizards and snakes.

Pulmonic Stenosis in a Bulldog

History: The dog was diagnosed with pulmonic stenosis by the cardiologist.

Gross lesions:  The right ventricular myocardium was severely thickened to about 7-10 times the normal width. The pulmonic outflow tract was markedly narrowed, and the pulmonary artery was dilated and had a very thin wall.

Heart: The right side of the heart is thickened to nearly the size of the left ventricular wall. The probe is going through the pulmonic outflow tract

Heart: The right ventricle, a wire is passing through the pulmonic valve into the pulmonary artery. The outflow tract is severely narrowed measuring about 2mm in diameter.

Heart: Viewed looking down onto the base of the heart. The probe is threading through a branch of a coronary artery that is encircling the pulmonic valve.

Comment:

A common cause of pulmonic stenosis in English Bulldogs results from a single right coronary artery which gives off a branch which encircles the pulomary artery causing a constriction.  This is called a “circumpulmonary left coronary artery”.

Other causes of pulmonic stenosis in dogs is valvular stenosis, which is very common, and is caused by malformed pulmonic valves. The valve develops abnormally in utero and becomes dome shaped with a central perforation.  The valve is unable to open properly during systole and causes occlusion of the outflow tract.

Another cause of PS is subvalvular stenosis, which is caused by a ring of fibrous tissue below the pulmonic valve, which constricts the outflow tract.

Gross lesions of pulmonic stenosis include: Right ventricular hypertrophy, post-stenotic dilatation of the pulmonary artery.  Pulmonic stenosis is inherited in Beagles and suspected to be inherited in English Bulldogs, Bull Mastiffs, Chihuahuas, and terriers.

Link Highlights-Path Wonk

Todays highlight is a great blog called Path Wonk:

This blog features cases from human pathology, particularly neuropathology and forensic pathology.  Here are examples of the cases featured on the blog.

• Cases are listed by date, and presented in the format of unknowns.
• Initial information are gross photos or case signalment and history, followed by links to the diagnosis.
• On the diagnosis pages are links to peer-reviewed articles about the subject.

You can find a link to Path Wonk on the right hand column under the histopath or pathology sections.

Enjoy.