Verlaufsuntersuchungen bei Deutschen Jagdterriern mit belastungsabhängiger metabolischer Myopathie

Zusammenfassung

Gegenstand und Ziel Die belastungsabhängige metabolische Myopathie beim Deutschen Jagdterrier ist eine autosomal-rezessive Erbkrankheit, die aufgrund einer Punktmutation zu einem Enzymdefekt der sehr langkettigen Acyl-CoA-Dehydrogenase führt und klinisch durch belastungsabhängige Schwäche, schwere Myalgien und Myoglobinurie charakterisiert ist. In dieser Studie wurde der klinische Verlauf der Erkrankung bei 9 betroffenen Deutschen Jagdterriern über 1 Jahr untersucht. Die Behandlung der Hunde umfasste die orale Supplementierung von L-Carnitin und Koenzym Q10 sowie eine Diät mit hohem Kohlenhydratgehalt und einem niedrigen Anteil an langkettigen Fettsäuren.

Material und Methode Die 9 Hunde mit nachgewiesenem Gendefekt wurden bei Auftreten der ersten Symptome (Messzeitpunkt 1, MZP1) und 1 Jahr später (Messzeitpunkt 2, MZP2) klinisch-neurologisch untersucht und es erfolgte eine Blutuntersuchung mit Analyse hämatologischer und klinisch-chemischer Parameter sowie der Konzentration des natriuretischen Peptids Typ B (NT-proBNP).

Ergebnisse Zum MZP2 zeigten die Hunde, wie bereits zum MZP1, nach Belastung ein steifes Gangbild, Muskelschwäche und -schmerz und hatten einen dunkelbraun verfärbten Urin. Bei den hämatologischen Parametern und der NT-proBNP-Konzentration ergaben sich, wie zum MZP1, keine Abweichungen vom Referenzbereich. Die Aktivitäten der Kreatinkinase und Alanin-Aminotransferase unterschieden sich statistisch nicht signifikant zwischen beiden MZP (p^CK = 0,31, p^ALT = 0,64). Nach Auswertung einer Besitzerbefragung und der klinisch-neurologischen Untersuchung der Hunde ließ sich im Rahmen der Verlaufsuntersuchung keine Verbesserung der myopathischen Beschwerden feststellen.

Schlussfolgerung und klinische Relevanz Die orale Supplementierung von L-Carnitin und Koenzym Q10 sowie spezielle diätetische Maßnahmen über 1 Jahr führten zu keiner Verbesserung der klinischen Symptomatik oder der untersuchten Laborparameter. Die Tiere zeigten keine progressive Verschlechterung der Symptomatik im Vergleich zur Erstvorstellung. Die Prognose ist jedoch als vorsichtig zu bezeichnen, da Daten zum Langzeitverlauf über einige Jahre fehlen. Unsere Ergebnisse bilden eine Grundlage für weitere Forschungen zu Lipidspeichermyopathien, insbesondere mit Fokus auf die belastungsabhängige metabolische Myopathie des Deutschen Jagdterriers, deren Therapie und eine entsprechende Zuchthygiene.

Abstract

Objective Exercise induced metabolic myopathy in German Hunting Terrier dogs is an autosomal-recessively inherited disorder, caused by a nonsense variant of the gene encoding for the very long-chain acyl-CoA-dehydrogenase (VLCAD) enzyme. Clinical signs include exercise- induced fatigue, muscle pain and weakness. In the present study, the long-term course of this disease was investigated over a period of 1 year in 9 affected German Hunting Terriers. The dogs were treated symptomatically with oral L-carnitine, coenzyme Q10 and a special diet characterized by a low content of long-chain fatty acids and a high proportion of carbohydrates.

Material and methods In 9 affected dogs, the phenotype as well as clinical, laboratory parameters, and histopathological findings are described (time point 1) and compared to follow-up examinations 1 year later (time point 2). At both time points clinical and neurological examinations, complete blood cell count, clinical chemistry profile and the concentration of brain natriuretic peptide (NT-proBNP) were investigated.

Results In the follow-up examinations, the same post-exercise clinical signs were present as in the initial presentation of the homozygous dogs. Dark-brownish discoloration of the urine, weakness, myalgia as well as stiff and tetraparetic gait were apparant. All hematological values and the concentration of NT-proBNP were within the relevant reference ranges. Plasma CK and ALT activities were compared between the first presentation and the follow- up examination and no significant differences were detected (p^CK = 0.31, p^ALT = 0.64). Signs of myopathy remained unchanged throughout the examination period.

Conclusion and clinical relevance Oral supplementation with L-carnitine, coenzyme Q10 and the special dietary management did not result in any improvement of clinical signs or laboratory parameters. No progression of the disease was observed. The prognosis for affected dogs remains cautious as long-term observations of affected dogs over several years are lacking. Our findings provide further important information on inherited disorders of mitochondrial β-oxidation in dogs, especially focused on the exercise induced metabolic myopathy in the German Hunting Terrier. This may provide new insights for novel treatment modalities in conjuntion with the development of improved breeding guidelines.

Schlüsselwörter

Hund - Very-long-Chain-Acyl-CoA-Dehydrogenase-Mangel (VLCAD) - myopathische Krise - β-Oxidation - Therapie

Key words

Dog - very long-chain acyl-CoA dehydrogenase deficiency - myopathic crisis - β-oxidation - therapy

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