MERRF syndrome

Synonyms Fukuhara syndrome

"ragged red fibers" in MERRF syndrome

Specialty Neurology

MERRF syndrome (or myoclonic epilepsy with ragged red fibers) is a mitochondrial disease. It
is extremely rare, and has varying degrees of expressivity owing to heteroplasmy.[1] MERRF
syndrome affects different parts of the body, particularly the muscles and nervous system.[2]
The signs and symptoms of this disorder appear at an early age, generally childhood or
adolescence. The causes of MERRF syndrome are difficult to determine, but because it is a
mitochondrial disorder, it can be caused by the mutation of nuclear DNA or mitochondrial
DNA.[3] The classification of this disease varies from patient to patient, since many individuals
do not fall into one specific disease category. The primary features displayed on a person with
MERRF include myoclonus, seizures, cerebellar ataxia, myopathy,[3] and ragged red fibers (RRF)
on muscle biopsy, leading to the disease's name. Secondary features include dementia, optic
atrophy, bilateral deafness, peripheral neuropathy, spasticity, or multiple lipomata.
Mitochondrial disorders, including MERRFS, may present at any age.[4

Symptoms[edit]
An individual displaying MERRFs syndrome will manifest not only a single symptom, but patients
regularly display more than one affected body part at a time. It has been observed that patients with
MERRF syndrome will primarily display myoclonus as a first symptom. There may also be seizures,
cerebellar ataxia and myopathy.[3] Secondary features include dementia, optic atrophy, bilateral
deafness, peripheral neuropathy, spasticity, or multiple lipomata. Additional symptoms include
dementia, optic atrophy, bilateral deafness and peripheral neuropathy, spasticity, lipomatosis, and/or
cardiomyopathy with Wolff Parkinson-White syndrome. Most patients will not exhibit all of these
symptoms, but more than one of these symptoms will be present in a patient who has been
diagnosed with MERRF disease. Due to the multiple symptoms presented by the individual, the
severity of the syndrome is very difficult to evaluate.[5] Mitochondrial disorders, including MERRF,
may present at any age. Therefore, if a patient is presenting some of these symptoms, the doctor is
able to narrow it down to MERRF mitochondrial disorder.

Causes[edit]

Mitochondrial inheritance

The cause of MERRF disorder is due to the mitochondrial genomes mutation. This means that it is a
pathogenic variants in mtDNA and is transmitted by maternal inheritance. Four point mutations in the
genome can be identified which are associated with MERRF: m.A8344G, m.T8356C, m.G8361A,
and m.G8363A. The point mutation m.A8344G is mostly associated with MERRF,[6] in a study
published by Paul Jose Lorenzoni from the Department of neurology at University of Panama[7]
stated that 80% of the patients with MERRF disease exhibited this point mutation. This point
mutation disrupts the mitochondrial gene for tRNA-Lys, thus disrupting the synthesis of proteins
essential for oxidative phosphorylation. The remaining mutations only account for 10% of cases, and
the remaining 10% of he patients with MERRF did not have an identifiable mutation in the
mitochondrial DNA.

Treatment and prognosis[edit]

Like many mitochondrial diseases, there is no cure for MERRF, no matter the means for diagnosis of
the disease. The treatment is primarily symptomatic. High doses of Coenzyme Q10, B complex
vitamins, and L-Carnitine are used for the altered metabolic processing that results in the disease.[9]
There is very little success with these treatments as therapies in hopes of improving mitochondrial
function.[15] The treatment only alleviates symptoms, and these do not prevent the disease from
progressing. Patients with concomitant disease, such as diabetes, deafness, or cardiac disease, are
treated in combination to manage symptoms.
Marasmus is a form of severe malnutrition characterized by energy deficiency. It can occur in
anyone with severe malnutrition but usually occurs in children.[1] A child with marasmus looks
emaciated. Body weight is reduced to less than 62% of the normal (expected) body weight for the
age.[2] Marasmus occurrence increases prior to age 1, whereas kwashiorkor occurrence increases
after 18 months. It can be distinguished from kwashiorkor in that kwashiorkor is protein deficiency
with adequate energy intake whereas marasmus is inadequate energy intake in all forms, including
protein. This clear-cut separation of marasmus and kwashiorkor is however not always clinically
evident as kwashiorkor is often seen in a context of insufficient caloric intake, and mixed clinical
pictures, called marasmic kwashiorkor, are possible. Protein wasting in kwashiorkor generally leads
to edema and ascites, while muscular wasting and loss of subcutaneous fat are the main clinical
signs of marasmus.[citation needed]
The prognosis is better than it is for kwashiorkor[3] but half of severely malnourished children die due
to unavailability of adequate treatment.[citation needed]
The word “marasmus” comes from the Greek μαρασμός marasmos ("withering").

Signs and symptoms[edit]

Buchenwald inmates, 16 April 1945 when camp was liberated

Marasmus is commonly represented by a shrunken, wasted appearance, loss of muscle mass and
subcutaneous fat mass.[4] Buttocks and upper limb muscle groups are usually more affected than
others. Edema is not a sign of marasmus and is present in only kwashiorkor and marasmic
kwashiorkor. Other symptoms of marasmus include unusual body temperature (hypothermia,
pyrexia); anemia; dehydration (as characterized with consistent thirst and shrunken eyes);
hypovolemic shock (weak radial pulse; cold extremities; decreased consciousness); tachypnea
(pneumonia, heart failure); abdominal manifestations (distension, decreased or metallic bowel
sounds; large or small liver; blood or mucus in the stools), ocular manifestations (corneal lesions
associated with vitamin A deficiency); dermal manifestations (evidence of infection, purpura, and
ear, nose, and throat symptoms (otitis, rhinitis).[citation needed] Dry skin and brittle hair are also symptoms
of marasmus. Marasmus can also make children short-tempered and irritable.[5]

Causes[edit]
Marasmus is caused by a severe deficiency of nearly all nutrients, especially protein, carbohydrates
and lipids, usually due to poverty and scarcity of food.[6] Viral, bacterial and parasitic infections can
cause children to absorb few nutrients, even when consumption is adequate.[7] Marasmus can
develop in children who have weakening conditions such as chronic diarrhea.[8]

Treatment[edit]
Both the causes and complications of the disorder must be treated, including infections, dehydration,
and circulation disorders, which are frequently lethal and lead to high mortality if ignored.[citation needed]
Initially, the child is given dried skim-milk powder mixed with boiled water, followed by the addition of
vegetable oils and, eventually, sugar. Refeeding must be done slowly to avoid refeeding syndrome.
Once children start to recover, they should have more balanced diets which meet their nutritional
needs. Children with marasmus commonly develop infections, and are consequently treated with
antibiotics.[9] Ultimately, marasmus can progress to the point of no return when the body's ability for
protein synthesis is lost. At this point, attempts to correct the disorder by giving food or protein are
futile.