Dilated cardiomyopathy with ataxia syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Dilated cardiomyopathy with ataxia (DCMA) syndrome is an inherited condition characterized by heart problems, movement difficulties, and other features affecting multiple body systems.

Beginning in infancy to early childhood, most people with DCMA syndrome develop dilated cardiomyopathy, which is a condition that weakens and enlarges the heart, preventing it from pumping blood efficiently. Some affected individuals also have long QT syndrome, which is a heart condition that causes the cardiac muscle to take longer than usual to recharge between beats. The irregular heartbeats (arrhythmia) can lead to fainting (syncope) or cardiac arrest and sudden death. Rarely, heart problems improve over time; however, in most cases of DCMA syndrome, affected individuals do not survive past childhood due to heart failure. A small percentage of people with DCMA syndrome have no heart problems at all.

By age 2, children with DCMA syndrome have problems with coordination and balance (ataxia). These movement problems can result in delay of motor skills such as standing and walking, but most older children with DCMA syndrome can walk without support.

In addition to heart problems and movement difficulties, most individuals with DCMA syndrome grow slowly before and after birth, which leads to short stature. Additionally, many affected individuals have mild intellectual disability. Many males with DCMA syndrome have genital abnormalities such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). Other common features of DCMA syndrome include unusually small red blood cells (microcytic anemia), which can cause pale skin; an abnormal buildup of fats in the liver (hepatic steatosis), which can damage the liver; and the degeneration of nerve cells that carry visual information from the eyes to the brain (optic nerve atrophy), which can lead to vision loss.

DCMA syndrome is associated with increased levels of a substance called 3-methylglutaconic acid in the urine. The amount of acid does not appear to influence the signs and symptoms of the condition. DCMA syndrome is one of a group of metabolic disorders that can be diagnosed by the presence of increased levels of 3-methylglutaconic acid in urine (3-methylglutaconic aciduria). People with DCMA syndrome also have high urine levels of another acid called 3-methylglutaric acid.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Mutations in the DNAJC19 gene cause DCMA syndrome. The DNAJC19 gene provides instructions for making a protein found in structures called mitochondria, which are the energy-producing centers of cells. While the exact function of the DNAJC19 protein is unclear, it may regulate the transport of other proteins into and out of mitochondria.

The DNAJC19 gene mutations that cause DCMA syndrome lead to the production of an abnormally shortened protein that likely has impaired function. Researchers speculate that a lack of functional DNAJC19 protein alters the transport of other proteins into and out of the mitochondria. When too many or too few proteins move in and out of the mitochondria, energy production and mitochondrial survival can be reduced. Tissues that have high energy demands, such as the heart and the brain, are especially susceptible to decreases in cellular energy production. It is likely that this loss of cellular energy damages these and other tissues, leading to heart problems, movement difficulties, and other features of DCMA syndrome.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

DCMA syndrome is a very rare disorder. Approximately 30 cases have been identified in the Dariusleut Hutterite population of the Great Plains region of Canada. Only a few affected individuals have been identified outside this population.

Which doctor should you see?

The suggested department for discussing Dilated cardiomyopathy with ataxia syndrome is Cardiology, with a cardiologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

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 the main concern heart structure, rhythm, circulation or another cause?
• Which symptoms should change the timing of follow-up?
• How would a proposed investigation change the care plan?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Dilated cardiomyopathy with ataxia syndrome. 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.

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.