Acatalasemia

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Acatalasemia is a condition characterized by very low levels of an enzyme called catalase. Many people with acatalasemia never have any health problems related to the condition and are diagnosed because they have affected family members.

Some of the first reported individuals with acatalasemia developed open sores (ulcers) inside the mouth that led to the death of soft tissue (gangrene). When mouth ulcers and gangrene occur with acatalasemia, the condition is known as Takahara disease. These complications are rarely seen in more recent cases of acatalasemia, probably because of improvements in oral hygiene.

Studies suggest that people with acatalasemia have an increased risk of developing type 2 diabetes, which is the most common form of diabetes. A higher percentage of people with acatalasemia have type 2 diabetes than in the general population, and the disease tends to develop at an earlier age (in a person's thirties or forties, on average). Researchers speculate that acatalasemia could also be a risk factor for other common, complex diseases; however, only a small number of cases have been studied.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the CAT gene can cause acatalasemia. This gene provides instructions for making the enzyme catalase, which breaks down hydrogen peroxide molecules into oxygen and water. Hydrogen peroxide is produced through chemical reactions within cells. At low levels, it is involved in several chemical signaling pathways, but at high levels it is toxic to cells. If hydrogen peroxide is not broken down by catalase, additional reactions convert it into compounds called reactive oxygen species that can damage DNA, proteins, and cell membranes.

Mutations in the CAT gene greatly reduce the activity of catalase. A shortage of this enzyme can allow hydrogen peroxide to build up to toxic levels in certain cells. For example, hydrogen peroxide produced by bacteria in the mouth may accumulate in and damage soft tissues, leading to mouth ulcers and gangrene. A buildup of hydrogen peroxide may also damage beta cells of the pancreas, which release a hormone called insulin that helps control blood glucose, also called blood sugar. Malfunctioning beta cells are thought to underlie the increased risk of type 2 diabetes in people with acatalasemia. It is unclear why some people have no health problems associated with a loss of catalase activity.

Many people with reduced catalase activity do not have an identified mutation in the CAT gene; in these cases, the cause of the condition is unknown. Researchers believe that other genetic and environmental factors can also influence the activity of catalase.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

Acatalasemia has an autosomal recessive pattern of inheritance, which means both copies of the CAT gene in each cell have mutations. When both copies of the gene are altered, the activity of catalase is reduced to less than 10 percent of normal.

When only one of the two copies of the CAT gene has a mutation, the activity of catalase is reduced by approximately half. This reduction in catalase activity is often called hypocatalasemia. Like acatalasemia, hypocatalasemia usually does not cause any health problems.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

More than 100 cases of acatalasemia have been reported in the medical literature. Researchers estimate that the condition occurs in about 1 in 12,500 people in Japan, 1 in 20,000 people in Hungary, and 1 in 25,000 people in Switzerland. The prevalence of acatalasemia in other populations is unknown.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Reduced catalase activity · Very frequent (99-80%)

Activity or concentration of catalase in the blood circulation below the lower limit of normal.

Oral ulcer · Frequent (79-30%)

Erosion of the mucous mebrane of the mouth with local excavation of the surface, resulting from the sloughing of inflammatory necrotic tissue.

Gangrene · Occasional (29-5%)

A serious and potentially life-threatening condition that arises when a considerable mass of body tissue dies (necrosis).

Gingival bleeding · Occasional (29-5%)

Hemorrhage affecting the gingiva.

Gingivitis · Occasional (29-5%)

Inflammation of the gingiva

Microcytic anemia · Occasional (29-5%)

A kind of anemia in which the volume of the red blood cells is reduced.

Severe periodontitis · Occasional (29-5%)

Increased susceptibility to periodontitis, as manifested by severe periodontal infection with rapid alveolar bone loss, tooth mobility, and premature tooth exfoliation.

Type II diabetes mellitus · Occasional (29-5%)

A type of diabetes mellitus initially characterized by insulin resistance and hyperinsulinemia and subsequently by glucose interolerance and hyperglycemia.

Other findings in the same source

From: Orphanet

Additional reported features include Old-aged sensorineural hearing impairment (Occasional (29-5%)); Arteriosclerosis (Very rare (<4-1%)); Pain (Very rare (<4-1%)); Parkinsonism (Very rare (<4-1%)); Premature loss of permanent teeth (Very rare (<4-1%)); Schizophrenia (Very rare (<4-1%)); Type I diabetes mellitus (Very rare (<4-1%)); Neoplasm of the larynx (Very rare (<4-1%)); Vitiligo (Very rare (<4-1%)). This is a selected summary, not a complete description of the condition.

Which doctor should you see?

The suggested department for discussing Acatalasemia is Metabolic Medicine, with a metabolic specialist / clinical geneticist as the relevant type of clinician. Paediatrician (children) or physician (adults), with metabolic specialist / clinical geneticist referral.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• Is a biochemical or molecular result needed to clarify the diagnosis?
• Does this condition require an individual plan for illness or reduced food intake?
• Should nutrition advice come from a specialist metabolic dietitian?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Acatalasemia. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.