POLIP is an acronym that stands for:
Polyneuropathy, Ophthalmoplegia, Leukoencephalopathy, and
Chronic Intestinal Pseudoobstruction and consider a mitochondrial myopathy
characterized by a tetrad of progressive sensorimotor peripheral nerve disease. Other clinical
features include myopathy, diffuse leukoencephalopathy, and ptosis.
Myoneuro-Gastrointestinal Encephalopathy Syndrome; MNGIE
Very rare; 33 patients up to 1997.
There were suggestions that this disorder is
an autosomal recessive trait with pathology of the nuclear genome, probably
involving the control of the mitochondrial DNA replication (multiple
deletions of mitochondrial DNA). Sporadic cases were also reported. Recent
report of the MNGIE (mitochondrial neurogastrointestinal encephalomyopathy) locus at 22q13.32qter.
The precise etiology and pathophysiologic
significance of the mitochondrial DNA (mtDNA) deletions and the
heterogeneity of the modifications of the mtDNA remain unknown. A mutation
in the gene encoding thymidine phosphorylase possibly results in a defect of
cytochrome c oxidase in liver and muscle.
MRI and CT scans are consistent with leukodystrophy
involving the cerebral and cerebellar white matter. Histology shows
widespread endoneurial fibrosis and demyelination in the peripheral nervous
system. Muscle biopsy with histologic features of mitochondrial myopathy
(ragged red fibers, muscle fibers with increased succinate dehydrogenase
stain or ultrastructurally abnormal mitochondria). Biochemical examination
of the liver and muscle tissues reveals defect of cytochrome c oxidase
(complex IV of the respiratory chain). Nerve conduction and electromyographic (EMG) studies are
compatible with a sensorimotor neuropathy; quantitative EMG may show a
myogenic process. Southern blot analysis reveals multiple deletions of
Symptoms begin before age of 20 years. The first
signs are gastrointestinal symptoms (recurrent nausea, vomiting, or diarrhea
with intestinal dysmotility) in the majority of cases, or an
ophthalmoparesis in some cases. The neurologic manifestations are
predominantly outside the central nervous system (CNS); gastrointestinal (GI) dysmotility is a result of severe visceral
neuropathy. Gastrostomy or jejunostomy tube feeding may fail because of
dysmotility. Malabsorption with intermittent diarrhea and chronic
malnutrition ensues. Parenteral alimentation is often necessary. Lactic
acidosis after moderate glucose loads may occur. Prokinetic agents,
including erythromycin and cisapride, are unsuccessful in improving
intestinal motility. Visual disturbances may manifest as blepharoptosis and
ophthalmoparesis. Proximal muscle weakness and mild ataxia is common.
Neurosensory hearing loss, proximal myopathy with marked muscle atrophy,
polyneuropathy, and encephalopathy (with hypodense areas in the white matter
on MRI examination) are present. In addition, there also may be an autonomic
neuropathy. Electrocardiography may show cardiac conduction abnormalities.
Respiratory function may be severely affected. The prognosis is poor because
of a severe weight loss bordering on cachexia, with a mean survival age of
28.5 years. The prognosis seems to be worsened by a young age of onset.
The diagnosis of mitochondrial
disease should be considered in any child with a multisystem neurological
disorder or who is being investigated for hypotonia. Anesthesia-related
morbidity and mortality risk is essentially linked to the preoperative
status of the child, that is, the number and extent ...