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

• HOIP-AAD (HOIP-Associated Autoinflammatory Disorder)
• HOIP-Associated Autoinflammatory Disorder (HOIP-AAD)

What is HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia? (Definition/Background Information)

• HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia is a highly uncommon genetic disorder characterized by immune dysfunction, inflammation, and muscle and lymphatic vessel abnormalities
• This congenital disorder is also known as HOIP-Associated Autoinflammatory Disorder (HOIP-AAD), and presently, only one case has been reported in a female patient. The disorder is inherited in an autosomal recessive manner
• The primary cause of HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia 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 presentations of the disorder include recurrent fever, growth retardation, joint pain and swelling, muscular weakness, diarrhea, and edema. HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia may be diagnosed through a combination of clinical findings, laboratory tests, and genetic testing
• The treatment typically includes immunosuppressive therapy and management of symptoms such as fever and inflammation. The prognosis of HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia may depend on the severity of the symptoms and one’s response to treatment

Who gets HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia? (Age and Sex Distribution)

• HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia is an extremely rare genetic disorder that has only been reported in one female (to date)
• The manifestation of signs and symptoms occurred in the first month of life (congenital onset)
• No information is presently available on worldwide distribution and racial/ethnic groups at risk for the disorder
• Since the pattern of inheritance is autosomal recessive, males and females may be expected to be represented evenly

The disorder was reported in a 19-year-old female with disease onset in the first month of life. She had on unaffected brother.

What are the Risk Factors for HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia? (Predisposing Factors)

The risk factors for HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia include:

• Having a family history of the disorder is the main risk factor identified
• Inheriting two copies of the mutated HOIP gene, one from each parent, to develop 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

Note: With only one case reported, no other information about the risk factors is currently available.

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 HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia? (Etiology)

HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia is caused by mutations in the HOIP 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
• In the first reported patient, the mutation was found inherited in an autosomal recessive pattern. Therefore, the parents will not have any clinical manifestations and may remain unaffected

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 HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia?

The signs and symptoms of HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia include:

• Recurrent fever
• Joint pain and swelling
• Muscle weakness and wasting
• Lymphatic vessel abnormalities

How is HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia Diagnosed?

HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia may be diagnosed through a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition
• Laboratory tests
• Muscle biopsy
• Endoscopic examination of upper and lower gastrointestinal tract: A colonoscopy exam showed lymphatic vessel abnormalities in the patient’s intestines
• Genetic testing for defects in the affected 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 HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia?

Complications of HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia can include:

• Chronic inflammation
• Growth and developmental retardation
• T- and B- lymphocyte abnormalities
• Overall, reduced quality of life

How is HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia Treated?

The treatment of HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia typically includes immunosuppressive therapy and management of symptoms such as fever and inflammation.

How can HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia be Prevented?

Presently, it is not possible to prevent HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia as the cause is a genetic mutation. 

• 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 HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia? (Outcomes/Resolutions)

• The prognosis for HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia may depend on its severity and treatment response
• It is not possible to determine a prognosis for the disorder based on a single reported case

Additional and Relevant Useful Information for HOIP Immunodeficiency, Autoinflammation, with or without Muscle Amylopectinosis or Systemic Lymphangiectasia syndrome:

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

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