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Alpers' disease is an autosomal recessive genetic syndrome characterized by seizures, hepatopathy, and progressive cognitive impairment. It is caused by mutation in the POLG gene resulting in mitochondrial DNA depletion.
- Alpers disease was first described by a North-American neurologist named, Bernard Jacob Alpers in 1931.
- In 1970, Peter Richard Huttenlocher a pediatric neurologist and neuroscientist described more phenotypic features associated with the disease. 
- Alpers disease is also refered as Alpers–Huttenlocher syndrome.
- There is no established system for the classification of Alpers disease.
- Alpers disease is inherited in an autosomal recessive pattern.
- Mutation in POLG1 gene reduces polymerase gamma functionality resulting in defective mitochondrial DNA replication and causing depletion of mitochondrial DNA. 
- Heterozygous mutation of POLG1 gene causes classic and severe presentation of the disease at an early age of onset.
- Homozygous mutation results in the milder form with onset of symptoms in adolescence.
- Brain, liver and skeletal muscles are most involved due to high number of mitochondria.
Differentiating Alpers disease from other Diseases
- Alpers disease must be differentiated from other mitochondrial diseases caused POLG gene mutation:
Epidemiology and Demographics
- The prevalence of Alpers disease is approximately 1 per 100,000 individuals worldwide.
- Alpers disease affects men and women equally.
- Higher carrier frequency is seen in the Northern European population. Although, it is seen in other ethnic groups as well.
- There are no established risk factors for Alpers disease.
- There is insufficient evidence to recommend routine screening for Alpers disease.
Natural History, Complications, and Prognosis
- Common complications of Alpers disease include seizures, liver failure poor growth, infection-associated encephalopathy, increased muscle tone, gastrointesinal dysfunction, dilated cardiomyopathy, dementia, cortical blindness, spasticity, jaundice and/or ascites.
- The prognosis is generally poor, death usually occurs within ten years after diagnosis due to life threatening complications of the disease.
Diagnostic Study of Choice
- There are no established criteria for the diagnosis of Alpers disease. However, it usually manifests with a triad consist of refractory seizures, hepatopathy, and psychomotor regression.
- The diagnosis is established by testing for the POLG gene.
History and Symptoms
- Alpers disease has a bimodal age of onset. The majority cases present in first two years of life and the rest present between the ages of 2 and 25.
- Alpers disease is characterized by presence of refractory seizures, psychomotor regression and liver failure.
- Other symptoms may include hypoglycemia secondary to underlying liver disease, vision changes, migraines, hallucinations, cognitive impairment, depression, anxiety and/or ataxia.
- Common physical examination findings of Alpers disease include spasticity, ataxia, altered muscle tone.
- Other physical findings include poor growth, developmental delay, failure to thrive, and/or vision changes.
- There are no diagnostic laboratory findings associated with Alpers disease.
- However CSF lactate may be elevated in some cases due to respiratory chain disorder.
- There are no ECG findings associated with Alpers disease. However, cardiomyopathy may be one of the possible complications of Alpers disease.
- There are no x-ray findings associated with Alpers disease.
Echocardiography or Ultrasound
- MRI demonstrates gray matter involvement in regions with the highest metabolic activity.
- In most patients MRI demonstrated T2/FLAIR hyperintensities within the occipital region, basal ganglia, deep cerebellar nuclei, and thalamus.
Other Imaging Findings
- In areas of high diffusion signal, MR spectroscopy may show increased lactate signal intensity and decreased NAA signal intensity.
Other Diagnostic Studies
- Rhythmic high-amplitude delta with superimposed (poly)spikes(RHADS) on EEG are reported to be highly specific of Alpers disease.
- Other EEG finding includes abnormal, often assymetrical flash visual evoked potential (VEP).
- There is no treatment for Alpers disease and no way to slow its progression; the mainstay of therapy is supportive and palliative care, achieved by a multidisciplinary care team.
- Seizure management should be achieved by with drugs with newer generation drugs(lamotrigine, primidone, topiramate, oxcarbazepine) with low hepatic impact.
- Valproic acid should be avoided for seizure management as it can worsen liver disease.
- Physical therapy may help relieve spasticity.
- Occupational/speech therapies may also help with neurological deficits.
- Tracheostomy, gastric feeding tube, and/or artificial ventilation may be helpful once the disease progresses.
- Surgical intervention is not recommended for the management of Alpers disease.
- There are no established measures for the primary prevention of Alpers disease.
- There are no established measures for the secondary prevention of Alpers disease.
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