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

• CSIFD Syndrome
• SIFD Syndrome

What is Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays? (Definition/Background Information)

• Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (CSIFD or SIFD) is a rare genetic disorder characterized by the presence of sideroblastic anemia, a condition in which the body is unable to produce enough healthy red blood cells. It is also associated with immunodeficiency, recurrent fevers, failure to thrive, and developmental delays
• CSIFD Syndrome is caused by mutations in the TRNT1 gene. This gene provides instructions for attaching a specific group of nucleosides to RNA molecules. When the gene is abnormal, the assembly of RNA molecules is disrupted, leading to development of the disorder. A positive family history of the disorder is the main risk factor for developing CSIFD Syndrome
• Individuals with Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays may have low levels of white blood cells and platelets in blood, leading to increased susceptibility to infections and bleeding. The disorder is diagnosed by a hematologist or geneticist. Genetic testing is used to confirm the diagnosis. A bone marrow biopsy may be performed to examine the red blood cells and determine the cause and severity of the anemia
• The treatment of Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays may include blood transfusions, iron chelation therapy, antibiotics to prevent and treat infections, and therapy to address developmental delays. In some cases, bone marrow transplantation may be considered as a treatment option
• The prognosis can vary depending on the severity of the disorder and the effectiveness of treatment. In some cases, Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays can be managed with treatment, while in others, it can even be fatal. As CSIFD is a genetic disorder, presently there are no preventative measures available for the same

Who gets Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays? (Age and Sex Distribution)

• Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (CSIFD) is a rare disorder with congenital manifestation (seen at birth)
• It has been observed in both males and females
• The disorder has been reported in a small number of individuals worldwide. The actual frequency and possible population segments affected are unknown because of its rarity

What are the Risk Factors for Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays? (Predisposing Factors)

The main risk factor for developing Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (SIFD) include:

• Having a family history of SIFD
• Having a genetic mutation in the TRNT1 gene

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 Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays? (Etiology)

Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (SIFD) is caused by mutations in the TRNT1 gene.

• This gene provides instructions for making a protein that adds a trinucleotide, C-C-A, to RNA. In other words, to attach a specific group of nucleosides to RNA molecules, the pattern of cytosine-cytosine-adenosine (CCA)
• This enzyme is important for the correct modification of the genetic code on RNA for function in many cell types and organs.
• When the gene is abnormal, assembly of RNA molecules is disrupted, leading to development of the disorder

What are the Signs and Symptoms of Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays?

The signs and symptoms of Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (CSIFD) may include:

• Anemia: Low hemoglobin count
• Recurrent fevers
• Developmental delays
• Susceptibility to infections, particularly involving the lung
• Failure to thrive
• Hypotonia (floppy baby)
• Seizures
• Sensorineural hearing loss
• Retinitis pigmentosa
• Vomiting and diarrhea
• Multiple abdominal symptoms
• Hepatomegaly and splenomegaly

How is Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays Diagnosed?

Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (SIFD) is diagnosed by a pediatric hematologist, geneticist, or other pediatric specialist, based on the individual’s signs and symptoms, physical examination, and laboratory test results.

• Genetic testing may be used to confirm the diagnosis
• A bone marrow biopsy may also be performed to examine the individual’s red blood cells and determine the cause and severity of the anemia

During disease flares c-reactive protein (CRP), erythrocyte sedimentation ratio (ESR), ferritin, transferritin, and calciuria (urinary calcium levels) are elevated.

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 Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays?

The complications of Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (SIFD) may include:

• Low levels of white blood cells which can lead to increased susceptibility to infections; recurrent infections are noted
• Low levels of platelets, which can lead to increased susceptibility to bleeding
• In severe cases, the anemia can be life-threatening
• Organ damage leading to organ failure
• Dilated cardiomyopathy with cardiac failure that can be fatal
• Cerebral atrophy, cerebellar abnormalities with possible cerebellar-caused ataxia (unstable gait)

How is Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays Treated?

• Treatment for Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (CSIFD) may include:
  • Blood transfusions
  • Iron chelation therapy
  • Antibiotics to prevent and treat infections
  • Therapy to address developmental delays
• In some cases, bone marrow transplantation may be considered as a treatment option

How can Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays be Prevented?

• Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (SIFD) is a genetic disorder, and presently it cannot be prevented
• Genetic counseling may be recommended for individuals with a family history of the disorder

What is the Prognosis of Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays? (Outcomes/Resolutions)

• The prognosis for individuals with Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays (SIFD) depends on its severity and treatment effectiveness. This may vary from one individual to another
• In some cases, the condition can be managed with treatment, while in others it can be fatal

Additional and Relevant Useful Information for Congenital Sideroblastic Anemia with Immunodeficiency, Fevers, and Developmental Delays:

The following link is a useful resource for further information on rare diseases and disorders:

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