Felipedia

Hereditary Granulation Anomaly in Birman cats

The Birman is an exotic, longhaired breed of cat that has Siamese-type colouring but with four white paws (Fig. 1). Hirsch and Cunningham initially discovered that the neutrophils of some Birman cats contained fine, reddish-purple, cytoplasmic granules. The appearance of the granules was similar to the primary or azurophilic granules of promyelocytes. A large survey of Birman cats in Canada found that 36 of 78 Birman cats (46%) examined had the neutrophil granulation anomaly. The condition was inherited in an autosomal recessive manner, indicating that both parents must provide a gene to produce the anomaly and that this condition equally affects both males and females.

Figure 1. Birman cat with longhaired, Siamese-type colouring and four white paws.

Clinical Presentation

There are no specific clinical signs in affected cats. This hereditary anomaly of neutrophil granulation usually is a serendipitous finding during a routine complete blood cell count.

Overview of the Hereditary Neutrophil Granulation Anomaly

This inherited neutrophil granulation anomaly is an autosomal recessive condition that is observed in Birman cats without evidence of illness. On a Romanowsky (Wright, Giemsa, Leishmann, or Diff-Quik) stained peripheral blood smear, neutrophils contain small, cytoplasmic, reddish-purple granules (Fig. 2). Ultrastructural studies have indicated that these granules are of normal size. Furthermore, the granules fail to stain with Alcian blue or toluidine blue dyes, indicating that the granules do not contain mucopolysaccharide that is typical of certain hereditary storage diseases (mucopolysaccharidosis types VI and VII).

Figure 2. A pair of neutrophils in the blood of a Birman cat with the hereditary granulation anomaly. Notice the fine, reddish-purple, cytoplasmic granules (Wright's stain).

In all healthy cats, primary or azurophilic granules are observed microscopically in Romanowsky-stained promyelocytes (progranulocytes, Fig 3). However, these primary granules are diluted with subsequent mitosis and are indistinct at the myelocyte stage of development. Segmented neutrophils in Romanowsky-stained blood smears from healthy cats usually have colourless cytoplasm; stained granules cannot be discerned by light microscopy. In Birman cats with the granulation anomaly, azurophilic granules appear to persist in all neutrophils, including mature segmented neutrophils.

Figure 3. Promyelocyte in a bone marrow smear from a cat. Notice the prominent primary or azurophilic cytoplasmic granules that stain reddish-purple (Wright's stain). Figure 4. Pair of segmented neutrophils in the blood smear of a healthy cat. Notice the lobated nucleus, coarse chromatin pattern, and colorless cytoplasm (Wright's stain).

The presence of the hereditary neutrophil granulation anomaly of Birman cats is of no clinical consequence. Although the anomaly is interesting from a hematologic standpoint, an increased incidence of infection has not been observed. Furthermore, in vitro studies have demonstrated that neutrophils from affected Birman cats exhibit bactericidal activity against Escherichia coli that is comparable to that of neutrophils from healthy control cats.

Differential Diagnosis

Neutrophils from healthy cats usually have a segmented or lobated nucleus with a coarse chromatin pattern and colorless cytoplasm (Fig. 4). Conditions in cats associated with the presence of fine, eosinophilic to metachromatic, cytoplasmic inclusions within the neutrophils of cats include the following:

Toxic granulation in response to infection or severe inflammation
Hereditary neutrophil granulation anomaly of Birman cats
Persistent reddish granulation of neutrophils in non-Birman cats
Mucopolysaccharidosis (types VI and VII) and GM2-gangliosidosis
Chediak-Higashi syndrome

Each of these conditions is discussed briefly below except for the hereditary neutrophil granulation anomaly (Fig. 2) that has been reviewed above.

Toxic granulation is observed infrequently in Romanowsky-stained blood smears of cats (Fig. 5). Affected cytoplasmic granules stain reddish-purple. This condition is associated with severe infection or inflammation, but disappears when the underlying condition resolves. Toxic granules are primary granules that have retained their staining affinity due to inflammation of any cause that is severe enough to accelerate neutrophil production intensely. With an increased tissue demand for neutrophils, there is enhanced neutrophil turnover and toxic granulation may be observed. Other toxic changes such as cytoplasmic basophilia, cytoplasmic vacuolation, and Döhle bodies are observed more commonly.

Figure 5. A neutrophil with toxic granulation secondary to severe infection. Notice the fine reddish purple cytoplasmic granulation (Wright's stain).

Persistent reddish granulation of neutrophils (Fig. 6) that has been reported in four cats including a 10-year-old male Siamese, a 6-year-old male Siamese, a 13-year-old female Siamese, and a 2-year-old male Himalayan. All of these cats were healthy when neutrophil granulation was observed in stained blood films. The cytoplasmic granules were not metachromatic (purple) when stained with toluidine blue.3 Similar morphologic changes also have been observed in blood smears of some Abyssinian cats (Latimer, unpublished observations).

Figure 6. Persistent reddish granulation of neutrophils in an Abyssinian cat (Wright's stain).

Lysosomal storage diseases are characterized by the accumulation of mucopolysaccharides or lipid components within cellular lysosomes. In some of these diseases such as mucopolysaccharidosis (MPS) type VI, MPS type VII, and GM2-gangliosidosis, reddish-purple granules may be present within the cytoplasm of neutrophils that stain purple with toluidine blue dye (Fig. 7).4,5 The lysosomal system is the principal site of intracellular degradation of complex molecules. Any inherited enzymatic deficiency in the metabolic pathway inhibits the degradation of these large molecules. As intermediate products of catabolism are produced, they accumulate within lysosomes but cannot be further degraded because of the missing enzyme.3 MPS also is characterized by skeletal and corneal changes.2,3 These diseases are inherited in an autosomal recessive pattern.

Figure 7. Pair of neutrophils from a cat with mucopolysaccharidosis type VI. Notice the reddish cytoplasmic inclusions (Wright's stain).

Chediak-Higashi syndrome (Fig. 8) is another lysosomal disorder in cats. In this syndrome, the neutrophils as well as eosinophils and occasional lymphocytes contain large lysosomal granules that are visible on Romanowsky-stained blood smears. If all of the granules appear normal in size, Chediak-Higashi syndrome can excluded.

Figure 8. A pair of neutrophils in the blood of a cat with Chediak-Higashi syndrome. These granules are actually enlarged lysosomes (Wright's stain).

Summary

If distinct, reddish-purple, cytoplasmic granulation is observed in Romanowsky-stained neutrophils of a Birman cat, the hereditary neutrophil granulation anomaly of Birman cats should be considered in the differential diagnosis. This anomaly is transmitted as an autosomal recessive trait and is of no clinical consequence.

1. Latimer KS, Prasse KW: Leukocytes. In: Latimer KS, Mahaffey EA, Prasse KW: Duncan and Prasse's Veterinary Laboratory Medicine: Clinical Pathology, 4th ed. Iowa State Press, Ames, 2003, pp.46-79.
2. Hirsch VM, Cunningham TA: Hereditary anomaly of neutrophil granulation in Birman cats. Am J Vet Res 45:2170-2174; 1984.
3. Harvey JW: Atlas of Veterinary Hematology: Blood and Bone Marrow of Domestic Animals. W.B Saunders Co., Philadelphia, 2001, p. 54.
4. Ettinger SJ, Feldman EC (eds): Textbook of Veterinary Internal Medicine. Diseases of the Dog and Cat, 5th ed. W.B Saunders Co., Philadelphia, 2000, pp. 1842-1848.
5. Alroy J, Freden GO, Goyal V, Raghavan SS, Schunk KL: Morphology of leukocytes from cats affected with alpha-mannosidosis and mucopolysaccharidosis VI (MPS VI). Vet Pathol 26:294-302, 1989.
6. Tilley LP, Smith FWK: The 5-Minute Veterinary Consult: Canine and Feline, 2nd ed. Lippincott Williams and Wilkins, Philadelphia, 2000. pp. 172-173.