Leigh Syndrome Summary

Due to the large size of the human nuclear genome, most of the mutations occur in nuclear DNA sequences. In contrast, the mitochondrial genome is small (about 1/200 000 nuclear genome size), so the mutation should occur less frequently. Unlike the nuclear genes, there are thousands of the copies of mitochondrial genes in each human somatic cell. For some cells such as the brain or muscle, very intense oxidative phosphorylation is required, and hence they have larger amounts of mitochondria.

or this units discussion I will be writing about Leigh’s Disease. According to the National Institute of Neurological Disorders and Stroke (December 16, 2011), “Leigh’s disease is a rare inherited neurometabolic disorder that affects the central nervous system. This progressive disorder begins in infants between the ages of three months and two years. Rarely, it occurs in teenagers and adults. Leigh's disease can be caused by mutations in mitochondrial DNA or by deficiencies of an enzyme called pyruvate dehydrogenase. Symptoms of Leigh's disease usually progress rapidly. The earliest signs may be poor sucking ability,and the loss of head control and motor skills.These symptoms may be accompanied by loss of appetite, vomiting, irritability,

The most common cause of MT-DNA Associated Leigh Syndrome is a mutation of the MT-DNA in the patient’s genetics and is most directly related to a maternal genetic mutation, as MT-DNA is passed through egg cells.The mother of a patient diagnosed with this disease most often develop very little to no symptoms. ("Leigh Syndrome", 2016;Thorburn,2014). The likelihood of children having a MT-DNA mutation is 100%, if the mother's MT-DNA has the mutation. This is due to the fact that the genetic code of the mitochondria, as previously stated, is passed through DNA in the egg cell ("About Mitochondrial Disease", n.d.). This form of leigh’s syndrome is most commonly diagnosed within 3 - 12 months into life, and rarely presents in the teenage years into adulthood. According to Mito Action, 1 in 4000 Americans are born with a mitochondrial disease and of this approximately 25% are diagnosed with Mt-DNA Associated Leigh Syndrome ("About Mitochondrial Disease", n.d.).

Mitochondrial dysfunction and oxidative stress have been consistently observed in brains of PD patients. There is increasing pharmacological and genetic evidence sustain a link between PD and mitochondrial respiratory chain dysfunction, particular a deficit in mitochondrial complex I (Franco-Iborra et al., 2015). Accidental exposure to 1-methyl-4-phenyl-1,2,3,4-tetrahydropyridine (MPTP), an mitochondrial complex I inhibitor, has been known to result in acute and irreversible syndrome that was almost indistinguishable from PD (Calne and Langston, 1983; Langston and Ballard, 1983). Later on, mitochondrial complex I inhibition has been identified in the brains of sporadic PD patients (Schapira et al., 1990). In addition, chronic systemic inhibition of mitochondrial complex I by pesticide rotenone has been found to link to sporadic PD (Betarbet et al., 2000). Interestingly, mitochondrial complex I deficiency has been found not only in the postmortem substantia nigra but also in cerebral cortex (Schapira et al., 1990), which is consistent to the cortical glucose hypometabolism observed in PD patients. Indeed, the pathology of PD has been found to involve several brain regions other than the SNc and many neurotransmitters other than dopamine (Lang and Obeso, 2004a, b). PD models using MPTP and rotenone have now been used extensively in PD research (Beal,

Mitochondrial disorders may be caused by mutations which are acquired or inherited in mitochondrial DNA (mtDNA) or in nuclear genes that code for mitochondria. Disorders can also be a result of environmental stress, adverse

The hub of energy metabolism, the mitochondrion, is found in virtually all eukaryotic cells, with the exception being erythrocytes. The mitochondrion generates cellular energy in the form of adenosine triphosphate (ATP), mostly by means of the oxidative phosphorylation (OXPHOS) system that is located in the inner mitochondrial membrane. The respiratory chain (CI-CIV) and ATP synthase (CV) is collectively known as the OXPHOS system, encoded by both nuclear DNA (nDNA) and mitochondrial DNA (mtDNA). The number of mitochondria per cell, ranging from hundreds to thousands, is controlled by the energy requirements of specific tissues with the greatest abundance of mitochondria found in metabolic active tissue (Pieczenik and Neustadt, 2007). Mitochondrial disease is caused when there is a defect in any of the numerous mitochondrial pathways, due to spontaneous or inherited mutations. Respiratory chain deficiencies (RCDs) are the largest subgroup of mitochondrial disease and occur when one of the four respiratory chain complexes become impaired. RCDs are considered to be one of the most common

This is a progressive neurometabolic disorder which can be detected through an MRI when dead or dying tissue is visibly found on the brain. This disorder typically arises in infants during their first years of life, and unfortunately, usually results in the patient’s death within a few years, normally because of respiratory failure. Sometimes, however, symptoms arise during adulthood or worsen slowly over time. The first symptoms of Leigh syndrome are usually seen in infancy and they include diarrhea, vomiting, and trouble swallowing, which leads to eating problems as well as the inability to grow and gain weight at the expected

Mitochondria, dubbed the ‘powerhouse of the cell’, are a type of organelle present in most human cells. Their primary function is to generate Adenosine Triphosphate (ATP), the cell’s principal source of chemical energy. Unlike most other organelles, mitochondria store their own set of genetic material, distinct from the DNA situated in a cell’s nucleus. Although this ‘mitochondrial genome’ represents only 0.1% of a cell’s genetic information, it often plays a significant role in development.

Not only do clinicians need to work with other professionals, but they also need to be aware of the other comorbidities that may be present in Noonan Syndrome. Many studies listed other cognitive functions that may be impacted by NS, and depending on the nature of the function, it could have a negative impact on language and speech. “Identification of attention problems and other psychiatric comorbidities will be an important element in developing appropriate educational and treatment goals to benefit individuals with Noonan syndrome” (Pierpont et al., 2014, p.391). Since some links have been made between Noonan Syndrome and delays in attention skills, it is important to keep in mind these associated risks and their implication on language

Schizophrenia, a chronic severe disabling disorder of the brain affects 1% of the Americans. It stays among the top 10 incapacitating conditions worldwide for adults. In US the expense of treatment and loss of productivity are estimated to be above $60 billion annually. Symptoms are characterized by positive symptoms including delusions, hallucinations and disorganized thinking; negative symptoms including flat affect, asociality, avolition, anergia and anhedonia; cognitive symptoms including poor executive function, poor attention and poor working memory. The typical stages of schizophrenia include a prodromal, active and residual phase.

Circumstance: Liam will be healthy and free from severe impairments from diagnosed DisGeorge Syndrome. Ms. Smalls (MHP) and Mrs. Wigfall (MHS) discuss Liam’s progress in the home.

Besides the appearance of episodic focal inflammatory lesions, there is a more generalized and progressive disease process that results in slow axonal , neuronal degeneration and subsequent accumulation of neurologic disabilities. The pathogenesis of this neurodegenerative process is aurged to the mitochondrial dysfunction which could be a key contributing mechanism ( Su et al., 2013)

Tetra-Amelia syndrome is a very rare disorder characterized by the absence of all four limbs. (“Tetra” is the Greek word for “four”, and “Amelia” refers to the failure of an arm or leg to develop before birth.) This syndrome can also cause severe malformations of other parts of the body, including the face and head, heart, nervous system, and skeleton. The lungs are underdeveloped in many cases, which makes breathing difficult or impossible. Because children with tetra-amelia syndrome have such serious medical problems, most are stillborn or die shortly after birth. Tetra-Amelia syndrome has been reported in only a few families worldwide. Management of persons who survive will depend on the presence and severity of associated malformations

Fig. 5 A. Mean number of mitochondria/µm2 ± SEM within 80 µm of the soma for wildtype mitochondria (WT - red) and Rett syndrome mitochondria (RTT – blue), both after 10 days in vitro. B. Mean number of mitochondria/µm2 ± SEM within 16-32, 32-48, 48-64 and 64-80 µm of the soma for wildtype

A delusion where the person is alive but is firmly convinced they are dead. This is called Cotard delusion or walking corpse syndrome.