Alpers Syndrome

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Alpers Syndrome is caused by mutations (changes) in the polymerase gamma (POLG) gene. This gene allows the mitochondria to make its own DNA (often called mtDNA). The POLG gene is involved in the replication and repair of mtDNA. Mitochondria work as tiny power stations within the cells, supplying them with energy. In individuals with Alpers Syndrome, the faulty gene does not make enough mtDNA in the liver or brain. The cells cannot function properly without the energy supply from the mitochondria and this can lead to severe epilepsy, loss of developmental skills and liver failure. Certain stressors such as infections and drugs such as valproic acid can increase the onset (arrival) of symptoms.  

Alpers Syndrome is a rare disorder. The prevalence of the condition is estimated to be between 1 in 100,000 and 1 in 250,000.  

Symptoms usually start before the age of 2. However, in approximately 20% of cases they may begin at any point up until the age of 25. Symptoms can vary from patient to patient and not all individuals will have all the symptoms listed.  

 Initial symptoms include failure to grow or gain weight and neurological signs such as brief, shock-like jerks of a muscle or group of muscles, known as myoclonus or myoclonic jerks. The most prominent symptoms are seizures, which may be accompanied by progressive loss of developmental skills and intellectual capabilities. The seizures may just affect one part of the body (such as one arm) to start with, but later become generalised.  

Other neurological problems that may occur in Alpers Syndrome include: 

• Areflexia (a condition in which your muscles don’t respond to stimuli) 
• Ataxia (a group of disorders that affect co-ordination, balance and speech) 
• Choreoathetosis (involuntary movements) 
• Developmental regression (loss of developmental milestones) 
• Global developmental delay (significant delay in cognitive and physical development) 
• Microcephaly (small head circumference)  
• Muscular hypotonia (low or weak muscle tone)  
• Progressive spasticity (progressive weakness and stiffness of the legs)  
• Spastic paraparesis (a group of inherited disorders characterized by progressive weakness and stiffness of the legs) 
• Hearing loss 

 Some individuals may have visual loss because of degeneration of the optic nerve (optic atrophy). 

 The other major organ that is predominantly affected is the liver. Signs of liver disease include yellow colouring of the skin and whites of the eyes (jaundice), enlargement of the liver (felt as a mass in the upper right part of the abdomen), and easy bruising and bleeding. In rare cases liver disease may be the first sign of Alpers Syndrome. Liver disease usually progresses to liver failure. Liver failure and damage caused by recurrent seizures are the main cause of death in this disorder. Children with Alpers Syndrome do not usually live beyond the first decade of life. 

The diagnosis is usually made using a combination of a detailed history, clinical examination and a range of specialised tests. These tests include measurement of chemicals in the blood and urine. A lumbar puncture may be done so that metabolic testing can also be performed on the spinal fluid. Brain MRI, electroencephalogram (EEG) and nerve conduction studies, and specialist examination of the eyes, the ears and the heart may also be undertaken to provide clues to which mitochondrial disease is responsible for the child’s symptoms. A muscle biopsy may be taken to measure the activity of the mitochondrial energy-producing enzymes, and also the amount of the mitochondrial genes. In rare cases a liver biopsy may also be performed. The diagnosis is confirmed by genetic testing of DNA extracted from a blood sample, specifically looking at the sequence of the POLG gene.  

This is a progressive disorder and unfortunately there is no cure. Therefore, treatment is focused on managing individual symptoms and providing comfort and relief in the form of supporting the individual and any family members. A multi-disciplinary team of specialists and support networks will be involved in the management of the condition and to offer practical and emotional support. 

Although seizures in this condition are difficult to manage, medication such as anticonvulsants may be used except for valproate which should be avoided as it can increase the risk of liver failure. Physiotherapy may help increase muscle tone and/or relieve any muscle contractions. Advice may be given on exercise and positioning. 

The prognosis is poor. Individuals with this condition usually do not survive past the age of 10 years old.  

Alpers Syndrome is an inherited condition. Humans have chromosomes made up of DNA. Genes are pieces of DNA that carry the genetic information. Each chromosome may have several thousand genes. We inherit chromosomes from the egg of the mother and sperm of the father. The genes on those chromosomes carry the instructions that determine a person’s characteristics, which are a combination of the parents.  

The pattern of inheritance of Alpers Syndrome is autosomal recessive. This means that carriers of the condition do not have the disorder because the other gene of this pair is working normally. Parents of children with Alpers Syndrome are carriers.   

 When both parents are carriers, the risk to the baby in each pregnancy is:

•  25% chance (1 in 4) of developing the condition  
•  50% chance (1 in 2) for the baby to be a carrier of the condition  
•  25% chance (1 in 4) for the baby to have two working genes and neither have the condition nor be a carrier  

Genetic counselling will be offered to those affected by this condition and their family members.  

References are available on request. Please contact us by phoning 0845 241 2173 or emailing contact@metabolicsupportuk.org [Resource Library No: AEM016].