What are the other Names for this Condition? (Also known as/Synonyms)

• HOIL1-IDA Syndrome

What is HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle? (Definition/Background Information)

• HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) is a highly uncommon genetic disorder that affects multiple systems in the body, including the immune system, muscles, and bones
• The primary cause of HOIL1-IDA is a genetic mutation in the HOIP gene, which leads to a defect in the HOIP protein that results in the characteristic signs and symptoms of the disorder. The disorder manifests at birth and persists through life. It has been reported in three patients belonging to two unrelated families
• The signs and symptoms of HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle include recurrent infections, muscle weakness, joint pain, among other symptoms. Some may present amylopectinosis, a disorder characterized by abnormal deposits of a starch-like substance called amylopectin in the muscles and bones
• The treatment for HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle is focused on managing symptoms and preventing complications. This may include antibiotics to prevent and treat infection, and medications to reduce inflammation. The prognosis for individuals with HOIL1-IDA is generally guarded

Who gets HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle? (Age and Sex Distribution)

• HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) is an extremely rare genetic disorder that presents in infancy. Only a handful of cases have been reported
• Both males and females are likely to be affected, since it is an autosomal recessive disorder
• No information is presently available on worldwide distribution and racial/ethnic groups at risk for the disorder, since the disorder is rare

In the two families reported with children with HOIL1-IDA Syndrome, three children did not have the disease and three did.

What are the Risk Factors for HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle? (Predisposing Factors)

• HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle is a genetic disorder, and the only known risk factor is having a family history of the disorder
• The disorder may be more frequent in consanguineous pairings (closely related to each other), where the mother and father share significant genetic similarities

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle? (Etiology)

The primary cause of HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) is a genetic mutation in the HOIL1 gene.

• HOIP gene provides instructions for making the HOIP protein that plays a role in the LUBAC (Linear Ubiquitin Chain Assembly Complex) system. The genetic defect leads to instability in the LUBAC complex
• Since this complex participates in the regulation of inflammation and the immune response, LUBAC deficiency leads to altered inflammatory responses and immunodeficiency
• HOIL1-IDA is inherited in an autosomal recessive manner

Autosomal recessive inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle?

The signs and symptoms of HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) vary, but typically include:

• Recurrent infections
• Recurrent fevers
• Enlarged liver and spleen (hepatomegaly and splenomegaly)
• Oral ulcers
• Bone and joint pain
• Elevated inflammatory mediators

Individuals with HOIL1-IDA may also have amylopectinosis, a disorder characterized by abnormal deposits of a starch-like substance called amylopectin in the muscles and bones.

How is HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle Diagnosed?

HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) is diagnosed through a combination of the following:

• Blood tests, muscle biopsies, and imaging studies may be used to help in the diagnosis
• Genetic testing to confirm the presence of a mutation in the HOIL1 gene

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle?

Complications of HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) can include:

• Growth retardation
• Muscle atrophy causing muscle weakness
• Joint pain and other inflammatory symptoms
• Decreased quality of life

The disorder can result in early deaths.

How is HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle Treated?

The treatment for HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) is focused on managing the signs and symptoms and preventing complications.

These may include:

• Antibiotics to prevent and treat infections
• Infusions of intravenous immunoglobulins (IVIG)
• Physical therapy to maintain muscle strength
• Medications to reduce inflammation

How can HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle be Prevented?

HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) is caused by a genetic mutation, and therefore cannot be prevented.

• Genetic counseling and testing may be recommended for individuals with a family history of the disorder and couples planning to have children
• However, early diagnosis and appropriate treatment can help manage the symptoms and prevent complications

What is the Prognosis of HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle? (Outcomes/Resolutions)

The prognosis for individuals with HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle (HOIL1-IDA) varies from individual to individual.

• It typically depends on the severity of symptoms and the presence of any complications, but is typically guarded
• Intensive treatments are required for HOIL 1-IDA, as it is a multisystem disease
• Early mortality is possible: HOIL 1 Deficiency was fatal during infancy in two patients. One patient underwent a hematopoietic stem cell transplant

Additional and Relevant Useful Information for HOIL 1 Deficiency, Immunodeficiency, Autoinflammation and Amylopectinosis of Cardiac and/or Skeletal Muscle:

The following link is a useful resource for information on other rare conditions on DoveMed:

https://www.dovemed.com/diseases-conditions/rare-disorders/