LEIGH'S DISEASE
(Chinese definition below, after the English version)
Definition
Leigh syndrome is an early onset, progressive neurological disease that involves defects in the normal function of the mitochondria. The mitochondrion is a small organelle located in most cells and is responsible for producing energy for cells and tissues throughout the body.
Description
Leigh syndrome is caused by defective cellular respiration that supplies many tissues with energy. The disorder is severe and can be particularly difficult for family members, as infants are among the severely affected. Leigh syndrome is also known as necrotizing encephalopathy.
Demographics
Leigh syndrome is a very rare disease that affects different peoples relatively equally. Some studies have shown that more males are affected than females.
Causes and symptoms
In Leigh syndrome, symptoms usually develop within the first year of life; rarely, symptoms can develop during later childhood. The infant usually initially develops symptoms that include hypotonia (decreased muscle tone), vomiting, and ataxia (balance or coordination abnormalities). Overall, failure to grow and thrive is usually the primary reason parents seek medical help. Eventually, the infant experiences seizures, lactic acidosis (an excess of lactic acid, a normal product of carbohydrate metabolism, in the body), and respiratory and kidney impairment.
Various abnormalities of the eyes are also common in Leigh syndrome. Ophthalmoplegia (paralysis of some or all of the muscles of the eye) is a typical finding, along with optic atrophy (degeneration of the optic nerve) and pigmentary retinopathy, a disorder that eventually leads to blindness.
On the cellular level, persons with Leigh syndrome have an inability to produce ATP (an energy source for the cell) in the mitochondria. Tissues that are not provided with adequate energy replenishment usually die. Irreversible damage can occur first in cells requiring much energy, such as the brain, leading to mental impairments and developmental delay. Many parts of the brain are affected by the lack of ATP in Leigh disease, including the basal ganglia, which helps regulate motor performance; the brainstem, which controls the functions of breathing, swallowing, seeing, and hearing; and the cerebellum, which coordinates balance and voluntary muscle movement.
Several genetic causes explain how persons develop Leigh disease, and several genes are involved. These genes include defects found in nuclear DNA as well as the smaller, less widely known mitochondrial DNA. Genes from both genomes contribute to the normal function of the mitochondria. Mutations in genes from the nuclear and the mitochondrial DNA have both been implicated in Leigh disease.
Diagnosis
In general, diagnosis of Leigh syndrome is often difficult due to the broad variability in clinical symptoms as well as the many different genetic explanations that cause this disease. Genetic testing for specific nuclear or mitochondrial DNA mutation is helpful in this regard.
Laboratory studies can assist in the diagnosis of Leigh syndrome. A muscle biopsy often determines if there are abnormalities associated with the mitochondria. Additionally, as the mitochondria are responsible for producing energy, a deficiency in a protein complex that has an important function in the mitochondria is often detected. In Leigh syndrome, this deficiency is found in one of five complexes that make up the mitochondrial respiratory system. One of these complexes, complex IV, or cytochrome c oxidase (COX), is commonly deficient. Although a COX deficiency is associated with Leigh syndrome, it can also indicate other mitochondrial abnormalities. Similarly, there are mutations found in other complexes that can cause Leigh syndrome.
Treatment team
Treatment for Leigh syndrome is aimed at easing the disease-related symptoms and involves neurologists, pediatricians, clinical geneticists, nurses, and other related caretakers. Psychological counseling and support for family members caring for a child with Leigh disease is often encouraged.
Treatment
Currently, there is no treatment that is effective in slowing the progression of Leigh disease. Thiamine or vitamin B1 is usually given. Sodium bicarbonate may also be prescribed to help manage lactic acidosis.
Recovery and rehabilitation
As there is no cure for Leigh disease and the nature of the disorder is rapidly progressive, maintaining function for as long as possible is the primary focus rather than recovery. Physical therapists often assist in exercises designed to maintain strength and range of motion. As the disease progresses, occupational therapists can provide positioning devices for comfort.
Clinical trials
As of early 2004, there are no clinical trials to treat or cure Leigh syndrome. However, studies are underway to better understand all mitochondrial diseases in an effort to identify treatments and, eventually, a cure.
Prognosis
Soon after the onset of symptoms, the progression of Leigh disease is unrelentingly rapid. Death usually occurs from respiratory failure within two years following the initial symptoms, and usually by age six.
*information taken from Healthline.
前言： 童年期腦脊髓病變 (Leigh’s disease) 是一種罕見的神經代謝異常之遺傳疾病，其特色是中樞神經的退化。
病因學： 目前已知有四種造成退化性腦病變的遺傳因素
1.pyruvate dehydrogenase complex deficiency
2.Complex I deficiency
3.Complex IV (COX) deficiency
4.Complex V (ATPase) deficiency。
這些缺陷可能是透過體染色體隱性的遺傳方式，如 COX deficiency；或是X-linked的遺傳方式，如PDH Eα deficinecy；或是由母系遺傳而來，如 complex V deficiency。
臨床表徵： 童年期腦脊髓病變 (Leigh’s disease) 是一種急速惡化的疾病，經常開始於3個月至2歲之間。在小孩最常被注意到的症狀可能是吸允力差，頭部控制功能消失，及之前的一些運動技巧消失。這些症狀亦可能伴隨食慾變差、嘔吐、躁動不安、持續哭鬧或抽慉等。
隨著症狀的惡化，可能伴隨有全身無力、肌肉張力消失、乳酸中毒的發作。酸酸中毒是因乳酸堆積在腦部而影響呼吸和腎臟的功能。心臟的問題也可能發生。童年期 腦脊髓病變(Leigh’s disease)有少數的病例可能在青少年晚期或兒童期早期才發生，而這些病歷其疾病惡化的程度可能比典型的童年期腦脊髓病變(Leigh’s disease)來得慢。
診斷： (一)影像學檢查
電腦斷層或核磁共振掃描可見在基底核處有兩側對稱性的低信號區域。
(二)病理學發現
於視丘、基底核、被蓋(tegmental)的灰質區域、腦室周圍、大腦導水管外圍區域、及腦幹和脊柱的後側區域可見局部對稱性的壞死性區域。
(三)顯微鏡的發現
於這些海綿狀的病灶處可見神經細胞減少性的囊狀空洞化、去髓鞘化及血管性增生的現象。
(四)血清學檢查
Lactate值會升高。
治療： 1.最常用於治療童年期腦脊髓病變 (Leigh’s disease) 是服用thiamine（vitamin B1）。在一些有pyrurate dehydrogenase enzyme complex 減少的病人，則可給予高脂肪、低碳水化合物的飲食控制。
2.口服碳酸鈉或檸檬酸鈉(sodium citrate)也可用於治療乳酸中毒。
預後： 退化性腦病變 (Leigh’s disease) 的癒復極差。通常會在幾年後便死亡，偶而可見病人活至6~7歲，某些病人甚至可活至十幾歲。那些於第一次疾病發作之後存活下來的病人，大多不易完全復原，之後多會持續性地朝著同一方向逐漸惡化而終至死亡。
*information taken from Web Services for Genetic Disease
No comments:
Post a Comment