BATTEN DISEASE Diploma in In-service Education Working with People with a Visual Impairment Independence and Technical Skills Presented by Gudbjorg Arnadottir

BATTEN DISEASE Diploma in In-service Education Working with People with a Visual Impairment Independence and Technical Skills Presented by Gudbjorg Arnadottir 15.10.2007

Neuronal Ceroid Lipofuscinoses The online Medical Encyclopedia definition of NCL: The neuronal ceroid lipofuscinoses (NCLs) are a group of rare, inherited neurodegenerative disorders. NCL can cause blindness, mental retardation, and early death. NCL disorders involve a build-up of an abnormal material in the brain, lipofuscin.  Evidence suggests problems in the ability of brain cells to remove and recycle proteins. The term neurodegenerative means "deterioration“ of nerve cells The disorder may be evident at birth, but it is usually diagnosed much later. Children develop muscle incoordination (ataxia), walking problems, visual problems, retardation, and seizures. The younger the person is when the disease appears, the greater the risk for disability and early death.

Batten Disease Batten Disease was usually regarded as the juvenile form of NCL, but has now become the term for all forms of NCL The forms of NCL are classified by age of onset. They have the same basic cause, progression and outcome but are hereditarily different. Batten Disease is named after the British pediatrician Dr. Frederick Batten, who first described it in 1903. Batten Disease is the most common form of a group of disorders called Neuronal Ceroid Lipofuscinoses (or NCLs) and now that name is used to encompass all forms of NCL, although Batten Disease is usually regarded as the juvenile form of NCL

The four forms of NCL Infantile NCL begins between about 6 months and 2 years of age. Late Infantile NCL begins between ages 2 and 4. Juvenile NCL begins between the ages of 5 and 8 years of age. Adult NCL generally begins before the age of 40 There are four main types of NCL, including two forms that begin early in childhood and a very rare form that strikes adults. The symptoms are similar but they become apparent at different ages and progress at different rates.    Infantile NCL Affected children fail to thrive and have abnormally small heads . Also typical are short, sharp muscle contractions. Initial signs of this disorder include delayed psychomotor development with progressive deterioration, other motor disorders, or seizures. The infantile form has the most rapid progression and children usually die before the age of 5.   Late Infantile NCL The typical early signs are loss of muscle coordination (ataxia) and seizures along with progressive mental deterioration.. This form progresses rapidly and ends in death between ages 8 and 12.  Juvenile NCL The typical early signs are progressive vision loss, seizures, ataxia or clumsiness. This form progresses less rapidly and typically ends in death in the late teens or early 20s,.   Adult NCL causes milder symptoms that progress slowly, and does not cause blindness. Although age of death is variable among affected individuals, this form does shorten life expectancy. 

Causes for Batten Disease Development of Batten Disease depends on both copies of a gene carrying the wrong plan for the same enzyme so that enzyme will not work In Batten Disease, parents carry the same faulty genes, and risk passing them on to their children The chance of a second child from the same parents developing Batten’s disease is one in four. By “recessive inheritance” a child with Batten Disease has by chance inherited a copy of the same gene from each parent The diseas is relatively rare. Batten Disease and Research Association in Australia (BDSRA) claim that it occurrs 2-4 of every 100.000 births in US while according to online NHS leaflet (UK) it occurrs in one of every 150.000 in UK, which demonstrates quite a difference. The disease appears to be more common in northern Europe, e.g. Finland and Sweden and in Canada and Newfoundland according to BDSRA. Contrary to the Juvenile and Infantile types of Batten, the adult type is onset by only one gene carrying the wrong plan, making it dominant inheritant. Although Batten is relatively rare, it often strikes the same family more than once (because of the defective gene carried). However it is claimed that a family can be affected by one type of NCL only.

The Eye The cornea focuses the light, which passes through the pupil. The light is then focused onto the back of the eye by a lens. The light sensitive photoreceptors cover the back of the eye collecting information in the retina. Each photoreceptor sends its signals to the brain via the optic nerves. All parts of the brain and eye need to be present and working for us to see normally. When you see an object, the light travels from that object to the cornea, then passes through the aqueous humour, pupil, lens and vitreous humour to reach the retina. During this passage, the light becomes focused onto the macula. At the macula, the light causes chemical reactions in the cones, that consequently send electrical messages from the eye to the brain. The brain recognises these messages and indicates to you that this particular object has been seen. The cones are therefore responsible for you being able to recognise colours and to read. The rods are essential for you to see in the dark, and to detect objects to the sides, above and below the object on which you are directly focused. This function prevents you from bumping into obstacles when moving around. All the retinal cells (rods and cones) are provided with oxygen and other nutrients from the retinal pigment cells (epithelium), which are kept supplied by the rich network of blood vessels in the choroid.

Function of the Eye Here you can see a diagram of the eye as described before. Point to cornea, aquous humour, pupil, lens, retina, macula. www.retinaaustralia.com.au/images/eye6.gif

Effects of Batten Disease Symptoms are linked to a build-up of lipopigments in the body tissues, e.g. in brain and eyes Disorder of the normal degradation of membrane and disorder in lipid metabolism in the cells lead to the accumulation of ceroid lipofuscin in the brain cells This will cause a damaging build up of fat and protein in cells, causing cells to switch off and die The distinguishing marks of Batten Disease are retinitis pigmentosa and neuronal degeneration Retinitis Pigmentosa is a group of retinal dystrophies that cause degeneration of the retina of the eye RP is a disease of the eye (in the retina), that the affected individual is born with. The word "pigmentosa" refers to a discoloration of the retina. The ceroid pigment is similar biochemically to materials accumulated more slowly during the normal ageing process. In Batten disease however, the accumulation is quite rapid and destructive. Neuronal degeneration is the deterioration of nerve cells in the body, to include the eyes.

Symptoms of Batten Disease Between ages of five to nine years: signs of clumsiness difficulty with school-work deteriorating vision - within a few years vision can be completely lost understanding and concentration become difficult Around ten years : The child may become unsteady and shaky Epileptic seizures will start Behaviour will be erratic and challenging The early symptoms may be slight and not obvious, such as behavioural changes and changes in personality. The child becomes slow in learning, clumsy or stumbles over things. Vision loss is often an early sign and the disease may be first suspected in examination of the vision. The disease cannot be diagnosed by this alone and it would be a neurologist that establishes the diagnose through medical history and laboratory tests.

Various Effects of Battens Disease Visual impairment, often progressing to blindness Seizures, frequent and difficult to control Decline in cognitive function Personality and behavioural changes Loss of communication skills Loss of fine and gross motor skills Abnormal body movements A general progressive deterioration Because of the variability of early symptoms and various age of onset it can be difficult to diagnose in the beginning. Sometimes children are mistakenly thought to suffer from epilepsy or mental retardation and adult have been labelled schizophrenics. But as the disease progresses the symptoms become clear.

Later Stages of the Disease The child will be unaware of the condition through later stages of the disease. Eventually the combination of the diseased brain and physical weakness becomes too great to sustain life Today Batten Disease always leads the patient to death. There is no treatment yet available that can stop the disease. Anti-convulsant drugs can be given to help control seizures and and other medical problems can be treated appropriately as they arise. At the same time, physical and occupational therapy can help patients retain function. treatment with vitamin supplements has been tried to slow down the disease in children with Batten disease , including dietary trials including fish oils and anti-oxidants. There are other studies also being carried out in the USA, UK, Australia and the Netherlands. However, so far these treatments have not prevented the final outcome of the disease.

References Medical Encyclopedia (2005) Retina http://www.nlm.nih.gov/medlineplus/ency/article/001613.htm (14.10.2007) Retina Australia (2001) Image www.retinaaustralia.com.au/images/eye6.gif (11.10.2007)