POLG-related disorders are a group of conditions that mainly cause muscle weakness, seizures, and liver failure.
Some people might start having symptoms as infants, while others may not show signs until adulthood. Even people in the same family can have different forms of POLG-related disorders, and sometimes symptoms can change over time. Here’s a breakdown of the different conditions associated with POLG-related disorders:
Alpers-Huttenlocher syndrome (AHS): AHS is the most severe condition; symptoms usually begin before age four and include recurring seizures that become harder to treat as time goes on. People with AHS may also have abnormal movements, lose their ability to think and remember, and develop liver disease.
Childhood Myocerebrohepatopathy Spectrum: MCHS usually starts before age three. Symptoms include developmental delays, memory and thinking problems, liver issues, a build-up of lactic acid in the body, and muscle weakness. Some people with MCHS may also have regular vomiting, hearing loss, pancreas problems, and kidney issues.
Ataxia Neuropathy Spectrum (ANS): ANS includes conditions like mitochondrial recessive ataxia syndrome (MIRAS) and sensory ataxia neuropathy dysarthria and ophthalmoplegia (SANDO). Symptoms can start anytime from early childhood to adulthood and may include balance and coordination problems (ataxia), nerve damage (neuropathy), seizures, and changes in brain structure. Other possible symptoms are blindness, sudden muscle jerks (myoclonus), liver problems, depression, and headaches.
Autosomal Recessive Progressive External Ophthalmoplegia (arPEO): arPEO usually begins in the teen years or early adulthood. It mainly causes eye muscle weakness that gets worse over time and makes it hard to exercise for long periods. Most people with arPEO don’t have other symptoms, but some may develop symptoms of ANS later on.
Myoclonic Epilepsy Myopathy Sensory Ataxia (MEMSA): MEMSA typically starts in young adulthood. It involves a range of symptoms, including muscle weakness (myopathy), seizures (epilepsy), and problems with balance and coordination (ataxia).
There is no cure for POLG-related disorders. Treatment is directed at managing an individual’s specific symptoms and supportive care.
This group of conditions is caused by pathogenic (disease-causing) variants in the POLG gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance of having a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background.
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Written August 2024
