[source]
pmid = PMID:19208399
title = A novel mutation in the VCP gene (G157R) in a German family with inclusion-body myopathy with Paget disease of bone and frontotemporal dementia
[diagnosis]
disease_id = OMIM:167320
disease_label = Inclusion body myopathy with early-onset Paget disease and frontotemporal dementia 1
[text]
Patient II-3. At the age of 41 years, the
male index patient developed slowly progressive symmetric muscle weakness, which started in the proximal upper limb muscles
but is now most pronounced in the proximal leg muscles. Three years
after onset he noticed increasing hearing impairment and bone pain. Elevated plasma levels of the
bone-specific alkaline phosphatase isoenzyme (168 g/L, normal 8 –17) in combination with typical
changes on a 99mTc total body bone scan suggested
a diagnosis of PDB. Biphosphonate treatment was
initiated and led to improvement of bone pain and a
marked reduction of alkaline phosphatase.
The muscle weakness, however, continued to increase, and
eventually the patient became unable to walk more
than 30 meters unaided. On examination, there was
proximal weakness and atrophy of the limb muscles
with bilateral scapular winging and a positive Trendelenburg sign. He had a waddling gait and required
the support of two crutches. The patient’s wife had
recently noticed an impaired capability of her husband to recognize faces of persons known to him. In
addition, he had become apathetic and had lost
interest in previous hobbies. Plasma creatine kinase
(CK) levels were mildly elevated. Nerve conduction
studies were normal, but electromyographic studies
showed moderate myopathic changes with fibrillation potentials and polyphasic small-amplitude,
short-duration motor unit potentials. Neuropsychological evaluation (DemTect, frontal assessment battery)
 did not show significant cognitive impairment. Audiometry revealed moderate left-sided
perceptive deafness of 50 dB HL. Cranial magnetic
resonance imaging (MRI) showed bony changes typical of Paget disease, but no evidence of auditory
nerve compression due to Paget disease. Intracranial
findings were normal without signs of frontal lobe
atrophy. A muscle biopsy from the quadriceps muscle revealed moderate histopathological changes
consisting of angulated and atrophic fibers with a
few inclusion bodies, but no rimmed vacuoles. The
inclusions were ubiquitin-positive, but they were negative for beta-amyloid. Ubiquitin-positive inclusions
could also be demonstrated in the nucleus of myocytes, endothelial cells, and fibroblasts.