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

• Congenital Deficiency of Intrinsic Factor
• Congenital Pernicious Anemia due to Defect of Intrinsic Factor
• Hereditary Juvenile Megaloblastic Anemia due to Intrinsic Factor Deficiency

What is Intrinsic Factor Deficiency Disorder? (Definition/Background Information)

• Intrinsic Factor Deficiency Disorder is a rare condition that is characterized by pernicious anemia and neurological abnormalities
• Most affected people develop signs and symptoms of the condition before age 5 years, which may include failure to thrive and symptoms related to anemia (i.e. fatigue, pale skin, etc.)
• Intrinsic Factor Deficiency is caused by changes (mutations) in the GIF gene and is inherited in an autosomal recessive manner
• Without early diagnosis and treatment, nervous system damage may occur, which can be associated with confusion; depression; and numbness or tingling in the hands and/or feet
• The treatment of Intrinsic Factor Deficiency Disorder generally consists of vitamin B12 injections

(Source: Intrinsic Factor Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

Who gets Intrinsic Factor Deficiency Disorder? (Age and Sex Distribution)

• Intrinsic Factor Deficiency Disorder is a rare congenital disorder, with less than 100 cases reported in the medical literature. Of these, about half have been confirmed as IFD Disorder at the molecular level
• The presentation of symptoms typically occur in early childhood, by the time the child turns 5 years old
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Intrinsic Factor Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Intrinsic Factor Deficiency Disorder can be inherited
• Currently, no other risk factors have been clearly identified for this disorder

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 Intrinsic Factor Deficiency Disorder? (Etiology)

• Intrinsic Factor Deficiency Disorder is caused by mutation(s) in the GIF gene that codes for the gastric intrinsic factor, which is important for the absorption of vitamin B12
• The GIF gene mutations causing IFD Disorder are inherited in an autosomal recessive manner

Autosomal recessive pattern of 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 Intrinsic Factor Deficiency Disorder?

The signs and symptoms of Intrinsic Factor Deficiency Disorder may include:

• Abnormality of the immune system
• Increased mean corpuscular volume
• Malabsorption
• Malabsorption of vitamin B12
• Megaloblastic anemia
• Megaloblastic erythroid hyperplasia
• Paresthesia
• Sensory impairment

(Source: Intrinsic Factor Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Intrinsic Factor Deficiency Disorder Diagnosed?

Intrinsic Factor Deficiency Disorder is diagnosed on the basis of the following information:

• Complete physical examination
• Thorough medical history evaluation
• Assessment of signs and symptoms
• Laboratory tests
• Imaging studies
• Biopsy studies, if necessary

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 Intrinsic Factor Deficiency Disorder?

The complications of Intrinsic Factor Deficiency Disorder typically develop in the absence of any suitable, and may include:

• Frequent infections
• Peripheral neuropathy
• Sub-acute degeneration of the spinal cord
• Abnormal gait
• Severe problems with movement
• Confusion
• Depression

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Intrinsic Factor Deficiency Disorder Treated?

• There is no cure for Intrinsic Factor Deficiency Disorder, since it is a genetic condition
• However, vitamin B12 injections are effective in symptom resolution and avoidance of complications

Note: The treatment for IFD Disorder with oral vitamin B12 is generally not preferred due to side effects of the oral medication, which may include muscle pain and vision problems.

How can Intrinsic Factor Deficiency Disorder be Prevented?

Currently, Intrinsic Factor Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy), if available, may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders

Regular medical screening at periodic intervals with tests and physical examinations are recommended.

What is the Prognosis of Intrinsic Factor Deficiency Disorder? (Outcomes/Resolutions)

• The prognosis of Intrinsic Factor Deficiency Disorder is good with an early diagnosis and prompt and sustained treatment
• However, without treatment, severe neurological and hematopoietic complications may ensue; under such circumstances, the affected individual may succumb to the condition

Additional and Relevant Useful Information for Intrinsic Factor Deficiency Disorder:

Intrinsic Factor Deficiency Disorder is also known by the following names: 

• Congenital Intrinsic Factor Deficiency Disorder
• Gastric Intrinsic Factor Deficiency Disorder
• IFD Disorder

The following DoveMed website link is a useful resource for additional information:

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