About fukuhara syndrome

What is fukuhara syndrome?

MERRF (Myoclonus Epilepsy with Ragged-Red Fibers) syndrome is an extremely rare disorder that begins in childhood and affects the nervous system and skeletal muscle as well as other body systems. The distinguishing feature in MERRF is myoclonus, consisting of sudden, brief, jerking spasms that can affect the arms and legs or the entire body. In addition, individuals with MERRF syndrome may have muscle weakness (myopathy), an impaired ability to coordinate movements (ataxia), seizures, and a slow deterioration of intellectual function (dementia). Short stature, degeneration of the optic nerve (optic atrophy), hearing loss, cardiomyopathy and abnormal sensation from nerve damage (peripheral neuropathy) are also common symptoms. Abnormal muscle cells are present and appear as ragged red fibers (RRF) when stained with the modified Gomori trichrome and viewed microscopically. MERRF is caused by mutations in mitochondrial DNA (mtDNA).

What are the symptoms for fukuhara syndrome?

Cardiomyopathy symptom was found in the fukuhara syndrome condition

Symptoms of MERRF syndrome can begin in childhood, adolescence or early adulthood after a period of normal early development. Signs, symptoms and physical findings associated with MERRF syndrome may vary greatly between affected individuals in the same family and between different families. The age of onset and how quickly the condition progresses can differ between individuals.

Brief, sudden, jerking Muscle Spasms (myoclonus) is usually the first symptom of MERRF syndrome followed by Seizures (generalized epilepsy), impaired ability to coordinate movements (ataxia), Muscle Weakness (myopathy) and exercise intolerance. Decreased body height (short stature), hearing loss, decline of intellectual function (dementia) and altered sensation (pins-and-needles or pain) from nerve damage (peripheral neuropathy) are also common symptoms. Some individuals may have vision problems or vision loss, most commonly caused by Degeneration of the optic nerve (optic atrophy). Vision impairment may also result from drooping upper eyelids (ptosis), progressive damage to the receptors that respond to light in the retina of the eye (pigmentary retinopathy) or Weakness of the eye muscles (ophthalmoplegia). Heart problems may also arise, including Heart disease of the heart muscle (cardiomyopathy) and problems of the heart rhythm (arrhythmia) such as Wolff-Parkinson-White syndrome. Occasionally, people with MERRF syndrome have benign fat cell tumors (lipomas) especially around the neck, too much sugar in the blood (diabetes mellitus) and involuntary Muscle Stiffness (spasticity) along with other differences in reflexes and movement (pyramidal signs). People with MERRF syndrome frequently have an accumulation of lactic acid in the blood (lactic acidosis) which can cause vomiting, abdominal pain, decreased appetite, unusual sleepiness or fatigue, muscle Pain or Weakness and difficulty breathing.

What are the causes for fukuhara syndrome?

MERRF syndrome is caused by genetic changes (mutations) in mitochondrial DNA (mtDNA). Mitochondria, which are found by the hundreds or thousands in the cells of the body, particularly in muscle and nerve tissue, carry the blueprints for regulating energy production. MtDNA encodes specific genes that are the instructions for making some of the essential parts of the mitochondria.

MERRF syndrome is caused by mutations in the mtDNA. The genes associated with MERRF syndrome are the instructions for specific molecules called transfer RNAs. Transfer RNAs (tRNAs) help assemble proteins, which then carry out the mitochondrial function of producing energy. Mutations in the mtDNA genes associated with MERRF lead to abnormal tRNAs, and consequently reduce the ability of the mitochondria to build proteins and produce energy for the body. Parts of the body that require a lot of energy, like the muscles and brain, will be the most affected by these mutations.

More than 90% of cases of MERRF syndrome are caused by mutations in one mtDNA gene, MT-TK. One specific MT-TK mutation, called m.8344A>G, accounts for 80% of cases. Mutations in MT-TF, MT-TH, MT-TI, MT-TL1, MT-TP, MT-TS1, and MT-TS2 have also been associated with MERRF syndrome.

Genes for mitochondria (mtDNA) are inherited from the mother. MtDNA that is found in sperm cells is typically lost during fertilization. As a result, all human mtDNA comes from the mother. A mother with a non-working gene in mtDNA will pass on the non-working gene to all her children, but only her daughters will pass on the non-working gene to their children.

As cells divide, the number of normal mtDNA and non-working (mutated) mtDNA are distributed in an unpredictable fashion among different tissues. Consequently, mutated mtDNA accumulates at different rates among different tissues in the same individual. Thus, family members who have the identical non-working gene in mtDNA may exhibit a variety of different symptoms at different times and with varying degrees of severity.

Both normal and mutated mtDNA can exist in the same cell, a situation known as heteroplasmy. The number of mitochondria with the non-working gene may be out-numbered by the number of mitochondria without the non-working gene. Symptoms may not appear in any given generation until a significant proportion of mitochondria have mutated mtDNA. The uneven distribution of normal and mutated mtDNA in different tissues can affect different organs in members of the same family. This can result in a variety of symptoms in affected family members.

It is generally thought that a higher number of mutated mtDNA relative to normal mtDNA corresponds with more severe symptoms. However, the number of mutated mtDNA relative to the normal mtDNAs cannot be used to accurately predict if symptoms will present, which symptoms may present or symptom severity.

A few rare cases of MERRF syndrome have occurred as the result of a new spontaneous mutation in a mitochondrial gene in the affected individual. These mutations are not inherited, but may be passed down to future generations if the affected individual is female.

What are the treatments for fukuhara syndrome?

No specific treatment is available for MERRF syndrome. Some medications and therapies may be helpful in managing symptoms.

Therapies are sometimes used to increase energy production by the mitochondria and slow the effects of the condition. Coenzyme Q10 (CoQ10) and L-carnitine have been beneficial in some patients with different mitochondrial diseases. Additionally, supplements such as ubiquinol, carnitine, alpha lipoic acid, vitamin E, vitamin B complex and creatine may be of benefit to some individuals with mitochondrial disease with muscle involvement. Efficacy of these supplements is being studied in clinical trials. Individuals with MERRF should avoid mitochondrial toxins such as aminoglycoside antibiotics, linezolid, cigarettes and alcohol.

What are the risk factors for fukuhara syndrome?

MERRF syndrome is a rare disorder that affects males and females in equal numbers. Onset of symptoms of MERRF syndrome can occur in childhood, adolescence or early adulthood. It typically presents after a period of normal early development.

The prevalence of MERRF syndrome is unknown. However, several studies of mitochondrial disorders in European populations found that the common MT-TK mutation, m.8344A>G, has a prevalence between 0 and 1.5 per 100,000 adults in northern Finland, 0.39 per 100,000 adults in northern England, between 0 and 0.25 per 100,000 children in western Sweden and 0.7 per 100,000 individuals in northeast England. Consistent with these findings, it is widely considered that the prevalence of MERRF is likely less than 1 per 100,000 individuals.

Some researchers believe that mitochondrial myopathies may go unrecognized and underdiagnosed in the general population, making it difficult to determine the true frequency of disorders like MERRF syndrome.

Is there a cure/medications for fukuhara syndrome?

Traditional anticonvulsant drugs are used to help prevent and control seizures associated with MERRF syndrome. Valproic acid should be avoided in the treatment of seizures. Levetiracetam and clonazepam have been effective in controlling myoclonus in a small number of patients. Standard treatment for heart problems (cardiomyopathies and arrhythmias) can be used per cardiologist recommendation. Hearing aids and cochlear implants can improve hearing impairments. Physical therapy, occupational therapy and aerobic exercise may help to improve muscle weakness, stiffness, and motor function.

Video related to fukuhara syndrome