Charcot-Marie tooth syndrome

Neuropathies can result from mutations that alter the structure or level of expression of PNS myelin proteins (e.g. overexpression of PMP22 in Charcot-Marie-Tooth syndrome (CMT) type 1A), the metabolism of myelin lipids (e.g. metachromatic leukodystrophy), or the capacity of PNS neurons to support their axons in patients with CMT caused by mutations of KIF1B [4] or NF-L [5, 6]. Both acquired and inherited amyloid neuropathies can result from the deposition of poorly soluble proteins, for example cryoglobulins or mutant transthyretins, in and around endoneurial bloodvessels [7-9]. 

The most common cause of primary demyelination is MS, so demyelinating optic neuropathy is often associated with MS. Other conditions have been implicated in demyelinating optic neuropathy, including acute transverse myelitis, acute disseminated encephalomyelitis, herpes zoster, Gnillain-Barre syndrome, Devic s nemomyelitis optica, Epstein-Barr virus, Charcot-Marie-Tooth syndrome, and chronic multifocal demyelinating nemopathy. 

The pathogenesis of vincristine-induced neuropathy has not been fully elucidated, but very probably altered axoplasmic transport processes are of major importance, since neurons treated with vincristine lose portions of their axonal microtubules (35). There is marked interindividual variability in sensitivity to this toxic effect, partially based on different predisposing factors, for example diabetes mellitus, pretreatment with other potentially neurotoxic agents (such as cisplatin and taxanes), or familial disorders (such as Charcot-Marie-Tooth syndrome) (37,51,52). 

Griffiths JD, Stark RJ, Ding JC, Cooper lA. Vincristine neurotoxicity in Charcot-Marie-Tooth syndrome. Med J Aust 1985 143(7) 305-6. 

Certain adverse reactions can also be associated with individuals who are carriers of rare disease genes, patients with compromised immune systems, and patients with certain chronic diseases. Peripheral neuropathy from anticancer drugs such as vincristine can be accelerated in specific patients with Charcot-Marie tooth syndrome [38], Park et al. [39] has discussed potential mechanisms that make HIV-positive patients more susceptible to enhanced drug toxicity, and Graham et al. [40] showed that the risk of developing rhab-domyolysis from statin-fibrin combinations increased significantly in older patients with diabetes mellitus. 

Begley MJ, Taylor GS, Kim SA et al (2003) Crystal structure of a phosphoinositide phosphatase, MTMR2 insights into myotubular myopathy and Charcot-Marie-Tooth syndrome. Mol Cell 12 1391-1402... 

Peripheral neuropathy is degeneration of peripheral nerves. Because motor and sensory axons tun in the same nerves, usually both motor and sensory functions are affected in this disease. Neuropathies may be either acute (e.g., Charcot-Marie-Tooth disease) or chronic (e.g., Guillain-Barre syndrome) and are categorized as demyelinating or axonal. 

Key words Motor neuron diseases, amyotrophic lateral sclerosis (ALS), spinal muscular atrophy (SMA), peripheral neuropathies, Charcot-Marie-Tooth diseases, hereditary motor and/or sensory neuropathies (HSMNs), congenital myasthenic syndromes, neuromuscular junction, muscular dystrophies, Duchenne s disease. 

In part two, we review the role of Pis in human disease. Although Pis are not abundant in biological systems, they have displayed numerous important functions in multiple signal transduction pathways. A number of human diseases are characterized by dysfunctional PI pathways, including cancer, type 2 diabetes, Lowe syndrome, myotubular myopathy, and Charcot-Marie-Tooth disease. 

Charcot-Marie-Tooth disease (GMT) is named after the three doctors who first described it in 1886, Professor Jean-Martin Charcot (pronounced sharko) (1825-1893), his student, Pierre Marie (1853-1940), who both worked in Paris at the Hospital de Salpetriere, and Dr. Howard Tooth (1856-1925) of London. It is also called peroneal muscular atrophy (PMA) because the peroneal muscle down the front of the shin that enables one to pull the foot up is usually the first muscle to be affected. A weakened peroneal muscle can cause sloppy walking or drop foot, which causes tripping. GMT also has a third and more recent name, hereditary motor and sensory neuropathy(HMSN). This name more accurately describes the syndrome because it is hereditary, can affect both or either the ability to move (motor) or the ability to feel (sensory). 

Stimulate appetite in AIDS Lambert-Eaton myasthenic syndrome and Charcot-Marie tooth disease Trypanosoma brucei gambiense (sleeping sickness) Pneumocystis carinii pneumonia in AIDS organ transplant recipients Corneal epithelial regeneration and healing Anemia associated with end-stage renal disease Anemia associated with end-stage renal disease Primary pulmonary hypertension Acute lymphocytic leukemia... 

Sideroblastic anemia j Aarskog-Scott syndrome PGK drficiency hemolytic anemia Charcot-Marie-Tooth disease Choroideremia Cleft palate, X-linked Spastic paraplegia, X-linked, 2 Deafness with stapes fixation 1 PRPS-related gout... 

Other demyelinating diseases also exist, and their cause is much more straightforward. These are relatively rare disorders. In all of these diseases, there is no fully effective treatment for the patient. Inherited mutations in Po (the major PNS myelin protein) leads to a version of Charcot-Marie-Tooth polyneuropathy syndrome. The inheritance pattern for this disease is autosomal dominant, indicating that the expression of one mutated allele will lead to expression of the disease. Mutations in PEP (the major myelin protein in the CNS) lead to Pelizaeus-Merzbacher disease and X-linked spastic paraplegia type 2 disease. These diseases display a wide range of phenotypes, from a lack of motor development and early death (most severe) to mild gait disturbances. The phenotype displayed depends on the precise location of the mutation within the protein. An altered function of either Po or PLP leads to demyelination and its subsequent clinical manifestations. 

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