MDR1 Mutation

TL;DR. Een veelvoorkomende genmutatie bij herdershonden schakelt een beschermend eiwit uit en maakt alledaagse middelen toxisch of fataal.

Shetland Sheepdogs are among the herding breeds highly predisposed to the MDR1 mutation.

Wat is het?

The MDR1 (ABCB1) mutation is a hereditary defect that impairs P-glycoprotein, an efflux pump concentrated at the blood-brain barrier and in liver, kidney, and gut. Without a working pump, many drugs accumulate in sensitive tissues and cause neurologic or organ toxicity at ordinary doses.

Oorzaken en risicofactoren

Autosomal incomplete dominant inheritance. Homozygous mutants lack functional P-glycoprotein; heterozygous carriers have reduced capacity and can still react at higher doses. Risk is breed-linked: Collie, Shetland Sheepdog, Australian Shepherd, Miniature American Shepherd, German Shepherd, Old English Sheepdog, Border Collie, English Shepherd, Whippet, Longhaired Whippet, Silken Windhound, and mixes with herding ancestry.

Signalen

• Vomiting, ataxia, lethargy, tremors, hypersalivation
• Depression, anorexia, mydriasis, diarrhea
• Bone marrow suppression (chemo substrates)
• Occasional: tachycardia, dehydration, seizures

"Common findings in dogs recorded in decreasing frequency included vomiting, ataxia, lethargy, tachycardia, hypersalivation, mydriasis, and seizures." - Plumb's Veterinary Drug Handbook, p.1982

Dilated pupils and severe lethargy are common clinical signs of drug toxicity in MDR1-affected dogs.

Diagnostiek

One-time MDR1 genetic testing (cheek swab or blood) classifies clear, carrier, or affected. In acute toxicity: history of drug exposure, neurologic exam, CBC/chemistry for organ support and marrow effects.

Intravenous fat emulsion (lipid rescue therapy) is used to reverse severe lipophilic drug toxicities.

Behandeling

No cure for the genotype. Acute exposure: decontamination if recent; Activated Charcoal; Intravenous Fat Emulsion for severe lipophilic toxicity (e.g. ivermectin); IV fluids, seizure control, intensive support. Lifelong: avoid or dose-adjust high-risk drugs (loperamide, high-dose ivermectin, some chemotherapeutics, acepromazine, butorphanol).

Prognose

Excellent if never exposed to problem drugs. Guarded after high-dose toxicity depending on drug, dose, speed of care, and access to lipid rescue.

Preventie

Test at-risk breeds and mixes before routine meds or chemo. Keep a contraindicated-drug list for every caretaker. Prefer MDR1-safe heartworm preventives when indicated.

Wanneer de dierenarts bellen

Emergency now: seizures, severe ataxia or inability to stand, stupor, non-reactive dilated pupils, uncontrolled drooling with vomiting after a suspect drug.

Voor specifieke rassen

Highest prevalence reported in Collies; also common in Shelties, Australian Shepherds, and Miniature American Shepherds. Appearance alone does not predict status; DNA test once.

Bronnen

• Plumb's Veterinary Drug Handbook, pages 1280, 1982, 2140.
• Small Animal Internal Medicine (5th Edition), page 1178.
• Small Animal Critical Care Medicine (2nd Edition), page 993.

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