Multi-disease genetic panel for the Cairn Terrier that brings together four molecular tests for classic hereditary diseases of the breed: pyruvate kinase deficiency (PK), globoid cell leukodystrophy (Krabbe disease), macrothrombocytopenia (MTC) and craniomandibular osteopathy (CMO). All four have a characterised molecular basis and their own pattern of inheritance. The panel complements haematological, neurological and orthopaedic monitoring in breeding selection.

Applicable breed: Cairn Terrier. TUBB1-related MTC has been described in the Cairn and Norfolk Terrier (and in the Cavalier KC with another variant); CMO in the Cairn, Scottish and West Highland White Terrier. Carrier frequencies in the breeding population are not published systematically (limited data); MTC is relatively common in Cairn and Norfolk lines.

- Chronic haemolytic anaemia with pale mucous membranes, lethargy and splenomegaly (PK)\n- Progressive neurological deterioration of the puppy: ataxia, tremor, paralysis (Krabbe)\n- Thrombocytopenia with giant platelets on the blood smear (MTC)\n- Possible haemorrhages, although MTC is usually asymptomatic\n- Mandibular pain and inability to open the mouth in the puppy (CMO)\n- Irregular bone thickening of the skull and mandible (CMO)

Canine Krabbe disease was characterised in the West Highland White Terrier and Cairn Terrier as globoid cell leukodystrophy due to galactocerebrosidase (GALC) deficiency, a natural model of the human form. Canine pyruvate kinase deficiency was associated with the PKLR gene in the Basenji and described in other breeds, including the Cairn Terrier. Macrothrombocytopenia of the Cairn and Norfolk Terrier was linked to a TUBB1 variant. Terrier craniomandibular osteopathy has been associated with variants in the SLC37A2 gene region (CFA5 chromosome); the exact pattern of inheritance remains a matter of discussion in the accessible literature.

- Genotype breeding animals before mating; the panel covers four conditions in a single sample\n- PK and Krabbe (recessive): do not cross carrier×carrier (25 % affected homozygotes); carrier×clear does not produce affected animals and offspring intended for breeding must be tested\n- MTC: as it does not cause relevant haemorrhage, it does not require breeding exclusion; inform the veterinarian to avoid erroneous diagnoses of thrombocytopenia\n- CMO (dominant with incomplete penetrance): avoid crossing two carriers; affected animals must not be bred\n- After a confirmed clinical case, do not repeat the parental cross and communicate the status to the buyer

PK is confirmed by erythrocyte enzymology and molecular testing; the condition must be differentiated from other haemolytic anaemias (immune, parasitic). Krabbe is confirmed by enzymology (GALC) in leukocytes and molecular study; the differential diagnosis includes other leukodystrophies and neuroaxonal dystrophies. MTC must be distinguished from pseudothrombocytopenia due to EDTA-dependent aggregates — repeat the smear in citrate. CMO is self-limiting at maturity but may require intense analgesia during the active phase; differentiate from osteomyelitis and mandibular neoplasia.

1. Whitney KM et al. The molecular basis of canine pyruvate kinase deficiency. Exp Hematol. 1994;22(9):866-874. PMID: 7520391.
2. Skelly BJ et al. Identification of a 6 base pair insertion in West Highland White Terriers with erythrocyte pyruvate kinase deficiency. Am J Vet Res. 1999;60(9):1169-1172. PMID: 10490091.
3. Victoria T et al. Cloning of the canine GALC cDNA and identification of the mutation causing globoid cell leukodystrophy in West Highland White and Cairn terriers. Genomics. 1996;33(3):457-462. PMID: 8661004.
4. Wenger DA et al. Globoid cell leukodystrophy in cairn and West Highland white terriers. J Hered. 1999;90(1):138-142. PMID: 9987921.
5. Gelain ME et al. A novel point mutation in the β1-tubulin gene in asymptomatic macrothrombocytopenic Norfolk and Cairn Terriers. Vet Clin Pathol. 2014;43(3):317-321. PMID: 25060661.
6. Hytönen MK et al. Molecular characterization of three canine models of human rare bone diseases: Caffey, van den Ende-Gupta, and Raine syndromes. PLoS Genet. 2016;12(5):e1006037. PMID: 27187611.
7. OMIA:000844-9615 (PK), OMIA:000578-9615 (Krabbe), OMIA:002434-9615 (MTC/TUBB1), OMIA:002244-9615 (CMO/SLC37A2).