Inclusion Body Myositis mit Morbus Paget und frontotemporaler Demenz: frühe Beteiligung des Herzens und der Atemmuskulatur

Zusammenfassung

Seitdem Mutationen im Valosin-containing Protein als einer der Auslöser einer Inclusion Body Myositis mit Morbus Paget des Knochens und frontotemporaler Demenz identifiziert wurden, wurden im letzten Jahrzehnt stets weitere Mutationen entdeckt. Wir berichten über einen 46-jährigen Patienten mit einer progressiven Tetraparese und autosomal-dominantem Vererbungsschema. Die Echokardiografie zeigte eine beginnende dilatative Kardiomyopathie. Laboranalysen demonstrierten eine erhöhte alkalische Phosphatase. In der neuropsychologischen Untersuchung ließen sich ein vermindertes verbales Gedächtnis und eine Einschränkung der Konzeptbildung zeigen. Die Muskelbiopsie zeigte ein myopathisches Bild, rimmed vacuoles, CD8 + T-Zellinfiltrate und MHC-1 positive Muskelfasern. Wir fanden eine heterozygote Mutation im Exon 5 des VCP-Gens (c.464G > T p.Arg155Leu), welche bislang nur in einer australischen Familie beschrieben wurde. Wir berichten hier den ersten deutschen Fall mit oben genannter Mutation, die mit einer Inclusion Body Myositis mit Morbus Paget des Knochens und frontotemporaler Demenz assoziiert ist. Ebenfalls zeigen wir die Notwendigkeit regelmäßiger kardiologischer und respiratorischer Kontrollen.

Abstract

Since valosin-containing protein mutations were reported as a cause of hereditary inclusion body myositis associated with Paget's disease of the bone and frontotemporal dementia, many new mutations have been described in the last decade. We report on a 46-year-old German male with a progressive tetraparesis and autosomal dominant inheritance pattern. Echocardiography revealed a beginning dilated cardiomyopathy and laboratory analyses showed increased alkaline phosphatase. Decreased verbal memory and an impairment of concept building were observed on neuropsychological examination. Muscle biopsy demonstrated a myopathic pattern, rimmed vacuoles, CD8 + T-cell infiltrates and positive MHC1-muscle fibres. We found a heterozygote mutation in exon 5 of the valosin-containing protein gene (c.464G > T p.Arg155Leu), which until now has been described only in an Australian family. We describe here the first German case with the above-mentioned mutation causing inclusion-body myositis associated with Paget's disease of the bone and fronto-temporal dementia. Here, we recommend regular controls of cardiac and respiratory functions.

Schlüsselwörter

Valosin-containing Protein - Inclusion body Myositis - frontotemporale Demenz - Morbus Paget des Knochens - Myopathie

Key words

valosin-containing protein - inclusion body myositis - fronto-temporal dementia - Paget’s disease of the bone - myopathy

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