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

• Lazy Leukocyte Syndrome
• Periodic Fever, Immunodeficiency, and Thrombocytopenia Syndrome (PFITS)
• PFIT Syndrome

What is Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia? (Definition/Background Information)

• Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia (APIT) is a rare genetic disorder that causes recurrent episodes of fever, skin rashes, joint pain, and chronic inflammation, as well as immunodeficiency and low platelet count (thrombocytopenia). The onset of symptoms is noted early in life
• The disorder is caused by mutations in the WDR1 gene and is inherited in an autosomal recessive manner. Thus, the risk factor for Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia includes a positive family history of the disorder
• This genetic disorder is typically diagnosed based on a combination of clinical examination, family history, blood tests including neutrophil motility and oxidative testing, and genetic testing for the WDR1 gene
• Initial treatment for Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia is typically symptomatic and supportive. Immunosuppressive and corticosteroid medications may have some effect on the symptoms. Platelet transfusions may be necessary for those with severe thrombocytopenia
• Currently, there are no available measures to prevent Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia as it is a genetic condition. Genetic counseling and testing may be recommended for individuals with a family history of APIT and couples planning to have children
• The prognosis of Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia is generally guarded; early deaths are known to occur. Hematopoietic stem cell transplantation may be curative

Who gets Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia? (Age and Sex Distribution)

• Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia is a rare disorder that manifests in children (congenitally)
• It affects both males and females
• Due to its rarity, information about its frequency and worldwide distribution is currently unavailable 

What are the Risk Factors for Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia? (Predisposing Factors)

The risk factors for Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia (APIT) include:

• Having a family history of the disorder
• Inheriting two copies of the mutated WDR1 gene, one from each parent, to develop the disorder
• APIT may be more frequent in consanguineous pairings (closely related to each other), where the mother and father share significant genetic similarity

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 Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia? (Etiology)

Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia is a genetic disorder caused by mutations in the WDR1 gene.

• The WDR1 gene encodes the WD40 protein that regulates the actin (a muscle component) complex
• These mutations lead to abnormal functioning of the actin micromuscle complex (functioning entirely within individual cells)
• This can cause abnormal motility of the neutrophils, circulating white blood cells active against bacterial infections
• The disorder has an autosomal recessive pattern of transmission

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 Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia?

The signs and symptoms of Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia may include:

• Recurrent episodes of fever
• Chronic stomatitis: Chronic oral (mouth) inflammation which can lead to scarring, leading to a small mouth opening
• Inflammation of the oropharynx
• Immunodeficiency resulting in:
  • Poor defensive response to bacterial infections
  • Middle ear infections (chronic otitis media)
  • Multiple skin and pulmonary infections
• Thrombocytopenia (low platelet count)
• Lymphopenia (low blood lymphocytes) and/or neutrophilia/neutropenia (high or low blood neutrophil count)
• Slow development in some patients

How is Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia Diagnosed?

Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia is typically diagnosed based on a combination of the following:

• Clinical examination and assessment of presenting signs and symptoms
• Evaluation of family history of the condition
• Blood count, including platelets
• Special testing for neutrophil motility and oxidative burst (used to kill bacteria)
• Genetic testing for WDR1 mutations

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 Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia?

Complications of Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia may include the following:

• Immunodeficiency resulting in severe and recurrent bacterial and viral infections
• Failure to thrive (slow weight and height gain)
• Developmental delays
• Chronic stomatitis can make eating and dental care difficult

Severe cases of the disorder can result in early death.

How is Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia Treated?

Treatment for Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia is typically symptomatic and supportive and may include the following:

• Medications to reduce inflammation and prevent recurrent episodes such as:
  • Early and prolonged use of suitably selected antibiotics
  • Corticosteroids
• Platelet transfusions may be necessary for those with severe thrombocytopenia
• Heterologous hematopoietic bone marrow transplantation

How can Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia be Prevented?

Presently, it is not possible to prevent Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia 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 Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia? (Outcomes/Resolutions)

The prognosis for Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia is generally guarded. Early deaths have been reported in some cases.

• With appropriate and aggressive treatment, most individuals are known to have a reasonable quality of life
• However, the disorder can cause significant discomfort, disability, and pain if left untreated.

Additional and Relevant Useful Information for Autoinflammatory Periodic Fever, Immunodeficiency, and Thrombocytopenia:

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

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