Bladder

Urinary incontinence is unintentional passing of urine. There are several common types of this:

•  Stress incontinence – bladder leaking when under pressure, such as when you cough or laugh
• Urge incontinence – bladder leaking with or shortly after a sudden urge to urinate, sometimes called urgency or micturition urgency
• Overflow incontinence – frequent bladder leaking caused by an inability to fully empty the bladder, also called chronic urinary retention
• Total incontinence – bladder is unable to store any urine, causing constant or frequent leaking

Those with this condition should talk to their GP or continence service, who may suggest products such as incontinence pads and handheld urinals. There are a range of treatments available to tackle incontinence, with even the least invasive of these able to help those whose incontinence is caused by a leukodystrophy. These methods range from changing behaviour to try to train the bladder, to pelvic floor exercises to increase muscle strength. Changes to diet and lifestyle, such as reducing caffeine and alcohol or losing weight, can also ease incontinence issues.

Electrical stimulation can be used to stimulate and strengthen pelvic floor muscles, reducing stress and urge incontinence when repeated over several months. Women with these issues can opt for insertion of medical devices, either a urethral insert or pessary, to reduce symptoms. If these methods are ineffective, medication can be taken to relax bladder muscles and reduce symptoms – talk to your GP, continence service or a urologist about appropriate medication available. Botox injections into the bladder are an example of a suggested treatment if these other methods have not been successful and ultimately there are a number of surgical options for severe and persistent problems.

Bowel

Bowel incontinence, or faecal incontinence, is an inability to control bowel movements, leading to unexpected leakage of faeces. This can be accompanied by diarrhoea, constipation and gas and bloating. It can also lead to skin irritation, causing pain, itching and potentially to painful ulcers. It is therefore important to seek treatment before this happens.

Treatments for bowel incontinence are very similar to those for bladder incontinence, from incontinence pads to bowel training and nerve stimulation. A GP or continence service will be able to help with this. Increasing exercise, drinking more fluids and eating more high-fibre foods can also help. As with urinary incontinence, surgery is available for those with a severe and persistent problem not helped by other methods. In some cases, the bowel is made redundant by the introduction of a colostomy bag to collect stools.

Other Organ Involvement

The term for an enlarged liver is hepatomegaly, an enlarged spleen is called splenomegaly, and enlargement of both is known as hepatosplenomegaly. Visceromegaly is a general term for enlargement of the organs in the abdomen. Organ enlargement is caused by build up of protein, fat or other substances due to the underlying leukodystrophy.

Organ enlargement does not necessarily cause symptoms. When liver enlargement is a result of liver disease, symptoms can include brown urine, clay-coloured stools, a swollen or painful abdomen (belly), nausea and vomiting, fever, fatigue, itching and a yellowish (jaundiced) colour to the skin and eyes.

Leukodystrophies that may cause organs to enlarge are Alpha-Mannosidosis; Aicardi-Goutieres Syndrome; Cockayne Syndrome; D-Bifunctional Protein Deficiency; Fucosidosis; 3-Methylglutaconic aciduria type 1; Peroxisomal Acyl CoA Oxidase deficiency; Peroxisome Biogenesis Disorders; Sialic acid storage disorders.

Enlarged Organs

The term for an enlarged liver is hepatomegaly, an enlarged spleen is called splenomegaly, and enlargement of both is known as hepatosplenomegaly. Visceromegaly is a general term for enlargement of the organs in the abdomen. Organ enlargement is caused by build up of protein, fat or other substances due to the underlying leukodystrophy.

Organ enlargement does not necessarily cause symptoms. When liver enlargement is a result of liver disease, symptoms can include brown urine, clay-coloured stools, a swollen or painful abdomen (belly), nausea and vomiting, fever, fatigue, itching and a yellowish (jaundiced) colour to the skin and eyes.

Leukodystrophies that may cause organs to enlarge are

Alpha-Mannosidosis

Aicardi-Goutieres Syndrome

Cockayne Syndrome

D-Bifunctional Protein Deficiency

Fucosidosis

3-Methylglutaconic aciduria type 1

Peroxisomal Acyl CoA Oxidase deficiency

Peroxisome Biogenesis Disorders

Sialic acid storage disorders.

Infants

Infants affected by cognitive problems either do not develop the usual cognitive skills, or lose skills they have acquired. Signs of cognitive difficulties may include irritability, feeding difficulties, disturbed sleep, and failure to develop psychomotor skills (i.e. ability at physical tasks like feeding or grasping) and coordination. It’s important to remember that irritability and problems with feeding or sleeping are common issues with babies whether or not they have a leukodystrophy, and are not automatically signs of cognitive problems.

Cognitive problems in infants with leukodystrophies are normally permanent and progressive. However, in Leukoencephalopathy with thalamus and brainstem involvement and elevated lactate, some improvement in cognitive ability may be seen over time.

Children

Children with cognitive disabilities that began in infancy may continue to experience deterioration of their abilities. In some conditions, children initially develop normally but begin to lose cognitive skills at some time in childhood or adolescence. The onset of cognitive deterioration often causes changes in behaviour or personality, and increasing difficulties with school work. In some leukodystrophies the cognitive deterioration progresses until the child is left profoundly disabled. In other conditions  the deterioration may be less severe.

As children become adults, they will move from children’s (paediatric) health and other services to adult services. This process may begin when the child is as young as 14, but may be as late as 24 in some cases. See our transition information page for more details.

Adults

Some people with leukodystrophies will begin to experience cognitive deterioration in adulthood.

Memory loss is a common symptom of declining cognitive ability. Someone experiencing memory loss may forget the reality of what they are going through, causing periods of calm followed by panic as this information is remembered or reintroduced.

Severe cognitive deterioration and memory loss is known as dementia. People with dementia become increasingly dependent on others for personal care and wellbeing. Early signs of dementia include problems with language and judgement, disorientation, and difficulties with familiar tasks. In certain conditions, dementia can be triggered by a stroke (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy; Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy).

People with memory loss or dementia will need increasing amounts of support to perform everyday tasks. Helping someone with mild memory loss or the early stages of dementia to maintain their social life and continue with activities they enjoy can make a big difference to their sense of independence and self-confidence.

Mental Health and Psychiatric Problems

For adults and older children experiencing the beginnings of this process, the thought of losing cognitive ability can be terrifying. This can have a severe effect on mental health (link to mental health services), including depression and suicidal tendencies.

Personality changes, including increased tendency for aggressive behaviour, may occur in people experiencing cognitive deterioration. This can affect relationships and lead to increased isolation and vulnerability. Loss of judgement, loss of social inhibitions, poor concentration and loss of reasoning abilities all heighten this vulnerability and strain on relationships. Talking to people who understand this can be of great help. At Alex TLC we offer one-to-one support and peer support to individuals and families affected by dementia as a result of leukodystrophies.

Psychosis and hallucination can be an effect of cognitive changes in children and adults with some leukodystrophies (Alpha-Mannosidosis; Cerebrotendinous Xanthomatosis; Metachromatic Leukodystrophy). Schizophrenia is a possible consequence of Methylenetetrahydrofolate Reductase Deficiency, which may begin in childhood or adulthood. Mental health services can help with these conditions, through psychological treatments such as Cognitive Behavioural Therapy (CBT) or antipsychotic medication. For schizophrenia, Crisis Response Teams can be called out to help with acute incidents.

Epilepsy often occurs in children and adults with white matter disorders. Although these people have a higher chance of being treatment resistant than those who do not have a degenerative disease, there are a number of helpful treatment strategies that can be used to ameliorate the seizures- or even control them completely.

Seizures are a sudden electrical disturbance in the brain, causing changes in behaviour, movement, feelings and/or consciousness. Epilepsy is the tendency to have recurrent seizures.

A typical seizure lasts between 30 seconds and 2 minutes. If a seizure lasts over 5 minutes, it should be treated as a medical emergency. Emergency medical treatment should also be sought in the case of injury caused by falls while having a seizure; pregnant or diabetic people having a seizure; lack of return to consciousness / breathing after the seizure or if the seizure is immediately followed by another. High fevers and heat exhaustion around seizures should also result in medical advice being sought. See our care page for more information on the additional help you can receive to help to care for people who have recurrent seizures.

Different types of seizures are:

• Focal seizures – caused by electrical activity in one area of the brain, these may or may not involve a loss of awareness or consciousness.
• Generalised seizures – in which electrical activity has occurred in all areas of the brain. There are several types of generalised seizures:
• Absence
• Tonic
• Atonic or Drop seizures, causing loss of muscle control which may cause a sudden fall
• Clonic seizures, usually affecting the neck, face and arms and associated with repeated jerking muscle movements
• Myoclonic
• Tonic-Clonic

It can be difficult to recognise seizures in infants, as this may look very different to an adult seizure. The most common kind of seizure in infants is a febrile seizure, in which the infant’s limbs stiffen or twitch and their eyes roll. This is often caused by fever. Infants may also experience the types of seizure above.

Treatment for epilepsy can vary, from simply identifying and avoiding triggers to seizures, to surgery to remove the part of the brain which causes this activity. Anti-Epileptic Drugs (AEDs) are the most common treatment, and drug choice tends to target the type of seizure the child is having. As drug resistance is common in children with white-matter disorders it’s important to consider other treatment interventions.

The ketogenic diet may be recommended. High in fat, low in carbohydrate and with carefully controlled protein levels, this diet has been shown to have positive effects in adults and children with epilepsy. Its effectiveness in infants is being investigated. This method is used if other treatment for epilepsy proves ineffective, and should not be pursued without advice from dieticians and specialists.

Insertion of a small electrical device to stimulate nerves is another option, normally as a VNS (Vagus Nerve Stimulation) device, similar to a pacemaker.

The use of alternative therapies to ease symptoms of epilepsy is not scientifically proven, and you should not stop taking medication or other treatments without consulting a specialist. For those who find their seizures are triggered by stress, relaxation exercises such as yoga and meditation may provide some relief.

For more general information on epilepsy, including triggers and symptoms, see the Epilepsy Action website.

Head Size

Abnormalities in head size are quite common in leukodystrophies. Smaller than normal head size is called microcephaly and larger than normal is called macrocephaly.

• Microcephaly can be present at birth or can develop within the first few years of life. It occurs when the brain has stopped growing or has not developed properly. Microcephaly can be linked to cognitive issues, seizures and developmental delay. There is no treatment for microcephaly itself. Treatment focuses on reducing the impact of any cognitive and developmental difficulties the child has, and controlling seizures.

o Leukodystrophies that may have microcephaly as a symptom include Aicardi-Goutieres Syndrome, Cockayne Syndrome; 3-Methylglutaconic Aciduria type 1; Methylenetetrahydrofolate Reductase Deficiency; Oculodentodigital Dysplasia with cerebral white matter abnormalities; Pelizaeus-Merzbacher-Like Disease; RARS-related hypomyelination.

• Macrocephaly can also be linked to cognitive disability and delay, although some children with macrocephaly have no other symptoms. Rapid head growth may occur alongside slow growth of the rest of the body. Those with macrocephaly often have hydrocephalus, which is a build-up of cerebrospinal fluid in the brain. Treatment of macrocephaly focuses on managing any underlying causes, such as hydrocephalus, and reducing the impact of cognitive and developmental issues. Hydrocephalus can often be treated by inserting a tube and catheter (called a ‘shunt system’) to allow fluid to flow away from the brain.

o People with the following conditions may be affected by macrocephaly: Alpha-Mannosidosis; Alexander Disease (type 1); Canavan Disease; Glutaric Acidemia type 1; L-2-hydroxyglutaric aciduria.

o GM2 gangliosidosis and Megalencephalic Leukodystrophy with subcortical Cysts can have megalencephaly as a symptom. Megalencephaly is macrocephaly caused by an abnormally large brain. Again, treatment focuses on reducing the impact of cognitive and developmental issues and seizures: there is no cure for megalencephaly.

• Large fontanelles are a symptom of some leukodystrophies (D-Bifunctional Protein Deficiency; Glutaric Acidemia type 1; Zellweger Syndrome). Fontanelles are ‘soft spots’ on an infant’s head, caused by gaps in the bones of the skull. All infants have these for the first few months of life to allow brain growth and development, before the bones close. In some cases, large fontanelles may be due to hydrocephalus (abnormal levels of cerebrospinal fluid in the brain). Large fontanelles may take longer than normal to close.

Jawbone

A protruding upper or lower jawbone, known as prognathism, is a symptom of two leukodystrophies (Alpha-Mannosidosis; Cockayne Syndrome). Corrective jaw surgery is unlikely to be considered appropriate for those with a leukodystrophy.

Other conditions are affected by retrognathism, in which the jawbone is set back (D-Bifunctional Protein Deficiency). Retrognathism can affect an individual’s ability to chew food, and may also affect ability to breathe, especially when asleep. They may experience sleep apnoea, in which breathing stops for several seconds while sleeping. Surgery may be available for retrognathism if it is causing these problems.

A small jawbone, or micrognathism, can affect those with Sialic Acid Storage Disorders. It may cause feeding problems, and is also treatable with corrective surgery if appropriate.

Jaw conditions can affect dental development. Problems such as misalignment of the teeth can cause difficulties with chewing, biting and talking and an increased risk of tooth decay and gum disease.

Dental Issues

People with leukodystrophy may experience a range of dental problems. Some are caused by jaw abnormalities, as described above. Another condition is hypodontia (under-developed or missing teeth). This can occur in people with POLR1C-related leukodystrophy and Oculodentodigital Dysplasia with cerebral white matter abnormalities in particular. People with POLR3-related leukodystrophy may also have abnormal teeth.

• Any dental issues may affect an individual’s ability to talk, bite or chew. Dental surgery – including braces and tooth replacement with fillings, dentures or bridges – can help people with hypodontia by improving pronunciation and chewing ability.

• Dental problems can also cause pain. To avoid this, people with leukodystrophies should have regular dental appointments as far as is possible. See our Dental section in Condition Management.

Other facial abnormalities

Some leukodystrophies are associated with distinctive facial features. These can include a high, wide or protruding forehead, a flattened nasal bridge and broad nose, and large misshapen and/or low set ears. An unusually thin nose can also be a distinctive feature. Eyes may be sunken, far apart (hypertelorism) or notably small (microphthalmia), or eyelid closure may be poor. A small number of conditions are associated with cleft lip or cleft palate. For those with Fucosidosis, thickened lips and tongue may be evident. People with Sialic acid storage disorders may have anteverted (upturned) nostrils.

Conditions that may be affected by facial abnormalities include:

Alpha-Mannosidosis
Cockayne Syndrome
D-Bifunctional Protein Deficiency
Fucosidosis
Glutaric Acidemia type 1
Infantile Refsum’s Disease
Neonatal Adrenoleukodystrophy
Oculodentodigital Dysplasia with cerebral white matter abnormalities

Peroxisomal Acyl-CoA Oxidase Deficiency
Sialic Acid Storage Disorders
Zellweger Syndrome

Please see individual condition pages for more specific information.

Babies and young children

Babies with leukodystrophies can be affected by common feeding and digestive problems like colic, regurgitation and constipation, just as any infant can. But they may also face additional problems caused by the leukodystrophy. Feeding and/or digestive problems can lead to under-nutrition and slower than expected growth, which is why some children will need nutritional support such as supplements or tube feeding. If you are concerned about your child’s nutrition or their growth rate, ask to be referred to a dietician.

An infant who does not grow at the expected rate, with height and weight measurements lower than expected, is described as failing to thrive. This is an indicator of under nutrition, which for children with a leukodystrophy can be caused by difficulties with feeding or by a need for further nutrients and additional calories compared to those who do not have a genetic syndrome.

•  Swallowing problems and dental abnormalities can also cause feeding difficulties. There is more information on these below.
• Feeding problems in infants with a leukodystrophy can indicate reduced cognitive ability, as the infant is unable to concentrate and settle to feed (Aicardi-Goutieres Syndrome; Canavan Disease; HSPD1-related hypomyelination; Krabbe Disease; Leighs Disease; Mucolipidosis type IV; Peroxisome Biogenesis Disorders).
• Children with a genetic syndrome may need more nutrients and calories than other children of their age.

Swallowing problems (dysphagia)

Swallowing difficulties (known as dysphagia) can vary in severity, from struggling with certain foods or liquids, to not being able to swallow at all. People with dysphagia may cough or choke when eating or drinking, bring food back up, or feel that it is stuck in their throat. Other potential symptoms of dysphagia are gurgling, “wet” sounding voice when eating or drinking, and persistent drooling.

Dysphagia can lead to weight loss and to increased susceptibility to chest infection. Sometimes some food or drink can go into the lung instead of down the food pipe. This can cause a serious chest infection known as aspiration pneumonia.

People with dysphagia are also at increased risk of choking on food. Fear of choking can cause the person to avoid food and drink, leading to malnutrition or dehydration.

Treating dysphagia

Dysphagia often cannot be cured, but support and treatment are available to help manage it.

• Making foods easier to swallow is the first step. A dietician or speech and language therapist can advise on this.
• In some cases, speech and language therapists can help people learn new swallowing techniques.
• When swallowing difficulties are severe, tube feeding may be the best way for the affected person to get the nutrition they need. This can be in addition to normal eating, or can replace it.

Progressive deterioration caused by any leukodystrophy at any age can cause dysphagia. However, conditions that are particularly affected are Adrenoleukodystrophy; Alexander Disease type 2; Cerebral Autosomal Recessive Arteriopathy with Subcortical Infarcts and Leukoencephalopathy; Hypomyelination with Atrophy of the Basal ganglia and Cerebellum; Leighs Disease; Megalencephalic Leukodystrophy with subcortical Cysts; POLR3 related leukodystrophy

Dental abnormalities

Feeding and digestion can also be impaired by poor development of teeth, missing teeth, and recurrent decay. Dental abnormalities are most likely in Cockayne Syndrome, Oculodentodigital Dysplasia with cerebral white matter abnormalities or POLR3 related leukodystrophy. However, maintaining dental hygiene is important for everyone with a leukodystrophy, to reduce the risk of feeding and digestive difficulties, tooth ache and other problems. You can find out more about dental services here.

Hearing loss can be a disorientating and difficult symptom for those coping with a leukodystrophy. It can also be upsetting for family and friends, who find it increasingly difficult to communicate with their loved one. The leukodystrophies affected by hearing loss are primarily childhood-onset conditions, meaning that in many cases the child will either fail to develop hearing or else quickly lose it.

Newborns will generally respond to noise, either turning their head to noises or startling at sudden loud noises. Hearing sounds is crucial in developing language skills: babies aged around 3-4 months begin to vocalise vowels and consonants and to recognise different voices.

Children with progressive conditions such as leukodystrophies may not respond to noise or may lose this response. While this could indicate hearing loss, it may also be due to mobility difficulties or general low responsiveness. If you are concerned, ask your doctor to refer your child for a hearing evaluation. If hearing difficulties are identified, they should be treated as soon as possible.

Click here for services that can help with hearing impairment.

Sensorineural hearing loss, also called labyrinthine hearing loss is caused by problems with the hair cells in the ear which sense sound, or by neural dysfunction. The severity of this varies from complete deafness to mild comprehension difficulties, with some also experiencing ringing or buzzing in the ears (tinnitus).

Cortical hearing loss is loss of hearing due to damage to the auditory cortex of the brain. As there is no damage to the ear, hearing aids will not have an effect on this form of hearing loss.

Different kinds of hearing aids and implants are available depending on what part of the ear is affected. These can restore some hearing, depending on the type or severity of hearing loss. Talk to your doctor and hearing impairment service to find out if these are appropriate: please be aware that some of those with hearing loss caused by leukodystrophy will not benefit from the use of hearing aids or implants.

For those with severe hearing loss, communication can be difficult. Sign language and lip reading are common methods used to help with this, talk to your GP and hearing impairment service to find out more about how to learn and use these methods.

Most leukodystrophies will have some effect on mobility, to varying degrees and over varying periods of time. They can affect coordination, balance and ability to walk unaided, and some leukodystrophies eventually result in complete loss of mobility. Infants with some leukodystrophies may fail to develop motor skills such as the ability to sit unsupported or to control head movements.

Ataxia
Ataxia is a term for a group of disorders affecting balance, coordination and speech. Leukodystrophies are one of many possible causes of ataxia.

Low muscle tone (hypotonia)
Low muscle tone, known as hypotonia, occurs in many leukodystrophies. It most commonly occurs in infants, often before they reach 6 months old. Infants with this condition are described as “floppy” or limp. This may lead to difficulties with sucking or swallowing, and delays in meeting milestones such as sitting up, crawling and walking. Adults and older children may also suffer from hypotonia, which can show up as clumsiness, difficulties in lifting or reaching for objects, frequent falls and difficulties in getting up. Physiotherapy, occupational therapy and speech therapy may help manage the effects of hypotonia.

Hypertonia and spasticity
With hypertonia, the affected person has too much muscle tone, i.e. the muscles are too contracted. This makes the affected parts of the body stiff and difficult to move.
In some cases, hypotonia is followed by a dramatic increase in muscle tone, hypertonia, causing muscles to strongly contract in a fixed position. This causes stiffness, making movement difficult.

Spasticity is a type of hypertonia in which affected muscles undergo prolonged periods of contraction that are increased by movement. The effects range from tightness and stiffness to painful muscle contractions known as spasms. Spasticity can make physical activities difficult, from walking to picking up objects. In severe cases the muscle can become locked in one position; this is called a contracture. Early treatment can help to prevent contractures and there are a range of treatments available, including physiotherapy, medications, injections and surgery. Regular stretching as directed by physiotherapy is the mainstay of treatment.

Foot drop
Foot drop is a common early sign of mobility issues. Damage to the muscles and/or nerves that lift the front part of the foot cause the toes to drag on the ground when walking. This makes walking difficult and increases the risk of falls. Physiotherapy may help, and there are also supports available such as an ankle-foot brace (orthosis) to hold the foot in a strengthened position. Speak to an orthotics team to find out about braces, splints and other supports. If these methods prove ineffective, electrical nerve stimulation or surgery are further options.

When combined with limited ankle motion, this is called equinus.

Bone and skeletal problems
Mobility can also be affected by problems with bones, from poor bone development to osteoporosis (weak, brittle bones which are prone to fracture). Osteoporosis or low bone density (osteopenia) can affect people with Coats plus Syndrome, Nasu-Hakola Disease or Peroxisome Biogenesis Disorder.

Sideways curvature of the spine, known as scoliosis, can be a symptom of some leukodystrophies. Scoliosis can appear as visible sideways curvature of the spine, a lean to one side, uneven shoulders or hips, or shoulders or ribs sticking out on one side. Scoliosis usually starts in childhood or adolescence but can develop in adults. It does not always cause problems, and treatment may not be necessary. More severely affected children and adolescents may need to wear a back brace while they are growing, and in a few cases surgery may be needed.

Treating and living with mobility problems
For many of the symptoms which affect mobility, physiotherapy may be suggested as a means of relieving or slowing progression of symptoms. Physiotherapy will not be successful for everyone, and should be considered in light of the affected person’s capacity and pain levels. Alternative or complementary therapies may also be suggested; some people find these helpful but they should be used alongside, not instead of, care from medical professionals.

As difficulties with mobility progress, walking aids may be needed. Using a stick or other walking aid can be a good idea to help reduce the risk of falls. Contact Orthotics if splints or braces are required, and Wheelchair services when a chair becomes a consideration. There is a wide range of equipment available to help with mobility: see our mobility equipment page for further information.

Caring for people with severe mobility difficulties, particularly adults and older children, can be physically and mentally challenging. You may be eligible for additional support if you care for someone who is severely disabled; see our care page for more information. Respite services are also available, and are a valuable resource to help you to look after an affected loved one. Occupational therapy can help with adaptations to your home and routine to make the lives of people with severe disabilities and their carers easier.

The effect of leukodystrophies on sexual maturity and function is often overlooked, with opportunities for treatment of these symptoms missed due to stigma and embarrassment around discussing it. Some conditions cause development of sexual functions and onset of puberty to be slow or absent.

Delayed puberty
Some conditions cause development of sexual functions and onset of puberty to be delayed or absent.

For girls, delayed puberty is diagnosed when breasts development has not started by age 13, or periods have not started by age 15, or periods have not started by 4 years after initial breast growth.

For boys, delayed puberty is diagnosed when enlargement of the testicles has not started by age 14, or pubic hair has not appeared by age 15, or it is taking over 4 years to complete adult genital development.

Delayed puberty can be treated with medication if it is causing distress or other problems.

Hypogonadism (sex hormone deficiency)
In some conditions the testes or ovaries may not produce the normal amounts of male or female sex hormones (e.g. testosterone or oestrogen). This is called hypogonadism. It can be present in childhood or can start in adulthood. Hypogonadism can often be treated with hormone-based medications.

Fertility
All of the conditions listed above could cause infertility, but CLCN2-related leukodystrophy will have this effect only on males. The risk of infertility with Vanishing White Matter Disease is primarily for females.

Treatments for some leukodystrophies can affect fertility. Stem cell transplants, which can be used to treat those in the early stages of cerebral Adrenoleukodystrophy and Metachromatic Leukodystrophy, will most likely leave the patient infertile. In this case, where loss of fertility is predictable, reproductive options can be discussed in advance. For males who have gone through puberty, it may be possible to freeze sperm for later use.

Men or women with fertility problems should speak to a reproductive specialist about options for having children. These range from assisted reproduction techniques like in vitro fertilisation (IVF), to adoption or surrogacy. People with leukodystrophies may wish to speak to a genetic counsellor before trying to conceive. The genetic counsellor can explain the likelihood of the condition being passed on to any children, and about options for ensuring that future children are free of the leukodystrophy gene.

Fertility problems can have major psychological consequences, both for those coping with leukodystrophy and their partners. See our page on mental health support if you need help with this.

Erectile Dysfunction
Erectile dysfunction can occur in any neurological disorder, and may be due to physical and/or psychological factors. For those with a leukodystrophy, erectile dysfunction should prompt an endocrine review for hypogonadism.

Whether or not a person has a leukodystrophy, treatment for erectile dysfunction is much the same, so advice should be sought from a GP. If this is not successful, a local urology or neuro-urology referral may be helpful, and support is often also available from local hospital urology or gynaecology departments.

People with some leukodystrophies may struggle to learn language skills, or may lose these skills at any age as cognitive issues progress. Difficulty with speech as a child or adult will be frustrating for the affected person trying to communicate with those around them, and for carers trying to identify the needs of their loved one.

Speech difficulties have a variety of possible causes, including developmental delay, cognitive decline, brain damage, problems with the voice box or the muscles that create speech, and hearing problems.

• Dysarthria is the name given to speaking difficulty caused by damage or changes to the brain. In some cases dysarthria is linked to problems with intelligence or understanding, but in others the person’s cognitive ability is unaffected. Speech may be slurred, nasal or breathy, making it difficult to understand. Some people with dysarthria are unable to produce any intelligible words, or may speak in short, disjointed phrases. Difficulty with swallowing (dysphagia) can be present alongside dysarthria and can make speaking more difficult. See more about speech and language therapy here.

• Speech difficulty caused by effects of physical disorders of the mouth, tongue, throat, or vocal cords on sound or voice production is called dysphonia. Dysphonia affects the quality of the voice, which may sound strained, strangulated or hoarse. Spasmodic dysphonia is caused by spasms in the muscles of the larynx (voice box). People with Alexander Disease type 2 may experience dysphonia.

Treatment of speech difficulties
For help with speech difficulties, you should ask your doctor to refer you or your child to a speech and language therapist. As well as helping with speech itself, they will be able to advise you about communication aids such as speech apps.

Nystagmus

Nystagmus, or constant uncontrolled eye movements, is a common symptom of those leukodystrophies that affect vision. Nystagmus can be either congenital (present from birth or early infancy) or acquired (developing later in life).

People with nystagmus do not necessarily have severely reduced vision.  Many experience large variations, with vision worsening when eye movements increase in frequency or speed. The eye movements are not painful but may cause the eyes to feel tired and achy, particularly when doing tasks that require high concentration.

People who develop nystagmus over time (i.e. those with acquired nystagmus) often find that their brain has not adapted to the constant movements of their eyes. This gives them a constant and sometimes disabling sensation that everything is moving around them. This rarely happens to those who have nystagmus from birth.

There is no cure for nystagmus, but those affected should have regular eye tests so that issues like long or short sight can be addressed through glasses or contact lenses where appropriate.  This does not affect the nystagmus but makes sure that the person’s sight is as good as possible. Conditions which can be affected by nystagmus include:

Adult onset autosomal Dominant Leukodystrophy;

Alexander Disease type 2;

Giant Axonal Neuropathy;

Hypomyelination with Atrophy of the Basal ganglia and Cerebellum;

Hypomyelination with Brainstem and Spinal cord involvement and Leg spasticity;

HSPD1-related hypomyelination;

Leighs Disease;

Pelizaeus-Merzbacher-Like Disease;

Peroxisomal Acyl CoA Oxidase deficiency;

RARS related hypomyelination.

Cataracts

A cataract is when the lens of the eye become cloudy instead of transparent. This makes the vision cloudy or misty. Cataracts are common in leukodystrophies. Some conditions cause a baby to be born with cataracts, while in others cataracts develop over time. Cataracts can occur in one or both eyes. Depending on severity, cataracts may require surgery to remove the cloudy lens. This is the most common operation performed in the UK and has a high success rate. In some cases the surgeon fits a plastic replacement lens. In other cases, the affected person must use glasses or contact lenses. If cataracts are present from birth, the surgery is usually done in the first 2 months of life. Cerebrotendinous Xanthomatosis; Hypomyelination with Congenital Cataracts; POLR3 related leukodystrophy are the leukodystrophies most commonly affected by cataracts.

Strabismus (Squint)

Strabismus, or squint, occurs when one eye is fixed in one position, while the other looks forward. Without treatment, children with strabismus develop a ‘lazy eye’ (amblyopia), and vision in this eye deteriorates. Squint and lazy eye should be assessed and treated as soon as possible, otherwise vision problems can become permanent. Treatments for strabismus include corrective prescription glasses, wearing an eye patch to improve the vision in the lazy eye, and surgery. Surgery to adjust the position of the eye muscles is used if other treatment proves ineffective. It is usually done as day surgery.

Strabismus is most likely to affect those with the following conditions: Alpha-Mannosidosis; Oculodentodigital Dysplasia with cerebral white matter abnormalities; Peroxisomal Acyl CoA Oxidase deficiency.

Optic Atrophy

Optic atrophy is an abnormality in which the optic nerve (the nerve that carries signals from the eye to the brain) becomes damaged and its function deteriorates. This causes visual problems such as blurred vision, difficulties with colour or peripheral vision, reduced sharpness in vision, and in some cases blindness. There is no treatment for optic atrophy. Conditions most likely to be affected by optic atrophy are 3-Methylglutaconic Aciduria type 1; Peroxisomal Acyl CoA Oxidase deficiency; POLR3 related leukodystrophy; Vanishing White Matter Disease.