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Acatalasia

Ulcer in the back of the mouth. In Takahara's disease these ulcers may become gangrenous.

Acatalasia (also called acatalasemia, or Takahara's disease) is a rare autosomal recessive peroxisomal disorder caused by defects that lower or stop expression of the enzyme catalase.  A shortage of this enzyme allows hydrogen peroxide to build up to toxic levels in certain cells.  Hypocatesimia is the term used for heterozygotes of the defective gene resulting in a phenotypic expression of 50% normal catalase activity. Acatalasia may cause ulcers in the mouth that can lead to gangrene. When gangrene occurs the condition is termed Takahara's disease. Many individuals who have the homozygous mutation in the catalase gene will be asymptomatic and are only diagnosed with acatalasia because they have symptomatic family members. High frequency of type 2 diabetes in catalase deficient individuals has shown it is a risk factor for diabetes in Hungarian forms of the disease.

Catalase Structure

Genetic Basis

Acatalasia is caused by mutations in the catalase gene found on the short arm of chromosome 13. Multiple mutations have been found to cause Acatalasia. Splicing and frame shift mutations found cause a complete loss of catalase activity. Missense mutations that cause the disease decrease the affinity in the catalase binding site altering substrate or heme binding of the catalase enzyme. Japanese populations have two mutations that have been identified to cause acatalasemia. These forms have been termed acatatalasemia-1&2. The Hungarian acatalasemia has been attributed to four different acatalasemia mutations A, B, C and D. The genetic causes in other populations are undetermined.

Occurrence

As of February 2012 one hundred and eighteen cases have been diagnosed in 61 families. Researchers estimate that the condition occurs approximately in one in every 12,500 person in Japan, every 20,000th in Hungary, and every 20,000th person in Switzerland. Acatylasimia has also been diagnosed in Peruvian , German and Jewish populations and a single case has also been reported in China.

History

In 1948, Dr. Shigeo Takahara (1908–1994), a Japanese otolaryngologist first reported this disease. He had examined a 10 year old girl that had progressive mucosal gangrene after a previous operation.  He performed the peroxide test on the diseased gums and the blood became dark brown and the peroxide did not bubble as expected. He assumed he had used silver nitrate mistakenly and re-performed the experiment with hydrogen peroxide obtaining the same result. Four of seven siblings in the patient’s family also had gangrene which had the same reaction to hydrogen peroxide pointing to a genetic abnormality. Oral gangrene from acatylasimia became known as Takahara’s disease. Within a few years Hungarian and Swiss forms of the disease were discovered. Peruvian and German forms were discovered later in 1979 and 1999.

Treatment and Diagnosis

Acatalasia is diagnosed as a reduction in catalase activity to 10% or less than 113.3 ± 16.5 Milliunits per litre in erythrocytes. Takahara’s disease is caused by pneumococcus and streptococcus, in the gums that produce hydrogen peroxide. This hydrogen peroxide can’t be broken down by the catalase deficient cells and it will destroy hemoglobin in the blood. That causes a local malnutrition in the gums which develops into gangrene. Improvement of oral hygiene and nutrition has made this symptom from acatylasia uncommon. Acatalasia has been linked to an increase in oxidative stress in the body. Hydrogen peroxide is generated by oxidases performing oxygen reduction. When the amount of hydrogen peroxide created exceeds the ability of enzymes to decompose it, cell damage is caused.  This has been attributed to higher incidence of early onset type 2 diabetes though the mechanism in which it affects pancreatic cells is unknown. No specific treatment for acatalasia has been discovered.