Hereditary predisposition to disseminated infections by the Mycobacterium avium complex (MAC) described in the Miniature Schnauzer. Affected animals present a primary immunodeficiency due to CARD9 dysfunction, with progressive systemic mycobacterial infections appearing in adulthood and involvement of reticuloendothelial organs. It is the first spontaneous animal model of human CARD9 deficiency.

Affects the Miniature Schnauzer; the mutant CARD9 allele has been detected in the breed worldwide. The exact frequency of carriers in the population is not established.

- Persistent or recurrent fever
- Generalised lymphadenopathy
- Hepatosplenomegaly
- Weight loss and lethargy
- Disseminated MAC infections, progressive and resistant to conventional treatment
- Associated fungal infections in some cases (via Dectin-1/β-glucan)

Adult Miniature Schnauzers with progressive systemic MAC infections related to a common founder were detected, with a pattern compatible with autosomal recessive inheritance. A GWAS and homozygosity mapping with 8 infected dogs, 9 unaffected relatives and 160 breed controls identified an associated region on chromosome 9; whole-genome sequencing of 2 infected dogs identified a one-codon deletion in CARD9 (c.493_495del; p.Lys165del). The mutant allele was detected in Miniature Schnauzers worldwide and all the infected dogs analysed were homozygous (Mizukami et al., 2024).

- Genotype breeding animals (CARD9 test available in the laboratories of the study)
- Do not mate carrier × carrier (25% homozygotes)
- An affected homozygote must not be bred; carrier × free does not produce affected animals and yields 50% carriers
- Communicate the genetic status to the buyer
- Suspect MAC in the presence of resistant systemic infections in the breed and confirm microbiologically (culture/PCR)

The differential diagnosis includes other congenital immunodeficiencies and causes of disseminated infections (leishmaniosis, ehrlichiosis, environmental mycoses). Microbiological confirmation (MAC culture or PCR) is essential. Affected animals require prolonged antimicrobial treatment (e.g. clarithromycin and fluoroquinolones) and environmental control. CARD9 dysfunction affects immunity against mycobacteria and fungi, so fungal susceptibility should also be monitored.

1. Mizukami K, Dorsey-Oresto A, Raj K, et al. Increased susceptibility to Mycobacterium avium complex infection in miniature Schnauzer dogs caused by a codon deletion in CARD9. Sci Rep. 2024;14(1):10346. PMID: 38710903
2. Borrás P, Marfil MJ, Tellado M, et al. Mycobacterium Avium in Miniature Schnauzer From Argentina: A Series of Cases. Top Companion Anim Med. 2022;51:100698. PMID: 35985408
3. Ghielmetti G, Giger U. Mycobacterium avium: an Emerging Pathogen for Dog Breeds with Hereditary Immunodeficiencies. Curr Clin Microbiol Rep. 2020;7(3):67-80. PMID: 33842195