Renal involvement in chronic progressive external ophthalmoplegia

Chronic Progressive External Ophthalmoplegia (CPEO) is a rare disease, which is
characterized by a slowly progressive weakness of the extraocular muscles. CPEO
is a mitochondrial disorder, which means that the symptoms result from a defect
in the intracellular energy production.
Mitochondria contain a unique stand of mitochondrial DNA (mtDNA); most cases of
CPEO are caused by a mutation in this mtDNA. In mitochondrial disorders, normal
mtDNA commonly coexists with mutant mtDNA within each cell. This is called
heteroplasmy. A higher percentage of heteroplasmy means relatively more mutant
mtDNA and often more severe symptoms. The percentage of heteroplasmy (and
therefore the chance of finding a mutation) is commonly highest in skeletal
muscle, which is obtain through a muscle biopsy.

All cells contain mitochondria and therefore CPEO commonly causes involvement
of other organs, mainly those with a high energy demand (skeletal muscle,
brain, peripheral nerves and heart). Kidney*s also have a high energy demand
and indeed several case report mention renal involvement in mitochondrial
disorders including CPEO. The exact prevalence of renal failure in CPEO has
never been studied yet.

Polyneuropathy is a common feature of CPEO. Commonly it is attributed to the
direct effect of mitochondrial dysfunction on peripheral nerve function.
However, in the general population, a common cause of polyneuropathy is renal
failure.

The goal of this study is to answer the following questions:


1. Is the chance of detecting mtDNA mutations in blood or urine sediment as
high as in a (much more invasive) skeletal muscle biopsy sample?

2. What is the prevalence of renal failure in CPEO?

3. Is there a correlation between the prevalence of polyneuropathy and renal
failure in CPEO

All 40 patient, who were previously diagnosed in the Radboud University
Nijmegen Medical Centre with CPEO according to the clinical criteria, will be
invited to participate. If the patient is willing to participate, the
investigator mails the patient a container for collecting urine. Furthermore
the investigator will visit the patients at home for:

• taking medical history to evaluate the use of medication, which can influence
renal function as well as a possible family history of renal disease
• venipuncture for collection of blood sample
• measuring blood pressure
• measuring achilles tendon reflex and sense of vibration

The only significant burden associated with this study is the venipuncture;
adverse effect as a result of this are highly unlikely.
Genetical tests are only performed in patients, in whom the muscle biopsy
already revealed a pathogenic mtDNA mutation. This excludes the possibility
that patients will unwittingly receive a new genetical diagnosis.