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

• C1qD Disorder

What is C1q Deficiency Disorder? (Definition/Background Information)

• C1q Deficiency Disorder is an infrequently occurring congenital disorder with manifestations that include recurrent skin lesions, long-term infections, and the presence of autoimmune disorders, chiefly systemic lupus erythematosus (SLE). It is informed that over 90% of the cases are associated with SLE
• C1q Deficiency Disorder is a genetic disorder with autosomal recessive pattern of inheritance. It is caused by mutations in the C1QA, C1QB, or C1QC genes. Due to this, the C1q protein complex important for complement system activation is either abnormal or deficient, causing a set of associated signs and symptoms
• C1q Deficiency Disorder leads to chronic infections, such as ear infection (otitis media), urinary tract infection (UTIs)s, and oral infections, apart from skin lesions in the form of small blisters that aggravate on exposure to light, cataract, loss of scalp hair, including chronic glomerulonephritis and kidney failure
• A management of C1q Deficiency Disorder depends on the presentations and complications. It may include stem cell transplantation. Systemic lupus erythematosus is treated using corticosteroids and immunosuppressive medications. With intensive medical therapy and for mild cases, the prognosis may be favorable

Who gets C1q Deficiency Disorder? (Age and Sex Distribution)

• C1q Deficiency Disorder is a rare congenital disorder. The presentation of symptoms may occur in childhood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for C1q Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since C1q Deficiency Disorder can be inherited
• Children born to consanguineous parents may bear an increased risk of developing this deficiency disorder
• In addition, C1q Deficiency Disorder is known to be associated with the following conditions:
• Systemic lupus erythematosus - in about 93% of the cases
• Mesangial proliferative glomerulonephritis

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 C1q Deficiency Disorder? (Etiology)

C1q Deficiency Disorder is inherited in an autosomal recessive pattern. Mutations involving the C1QA, C1QB, or C1QC genes are noted in this disorder.

• These gene mutations cause disturbances in the C1q protein complex (C1q with C1r and C1s proteins), resulting in absent C1q protein or abnormal C1q protein
• The protein complex is vital for activation of the complement system that forms part of the immune system with responsibility of clearing pathogens and dead cells from the body

Autosomal recessive: 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 C1q Deficiency Disorder?

The signs and symptoms of C1q Deficiency Disorder may vary among affected individuals in type and severity. It also depends on the associated immune conditions. The presentations may include:

• Decreased serum complement factor I resulting in recurrent infections of the middle ear, urinary tract, and mouth
• Presence of small fluid-filled lesions (blisters or vesicles) that get worse under exposure to sunlight
• Dark skin patches
• Hair loss from the scalp and eyes (eyebrows and eyelashes)
• Cataracts
• Membranoproliferative glomerulonephritis with symptoms that include:
  • Frequent urination
  • Edema or swelling in the face, ankles, hands, and feet
  • Cloudy urine with blood or pus
  • Fever
  • Hypertension
• Systemic lupus erythematosus, if present, may lead to:
  • Skin rashes
  • Fatigue
  • Muscle and joint pain
  • Mouth sores
  • Sensitivity to sunlight
  • Inflammation of the heart and lungs linings
  • Chest pain
  • Enlarged lymph nodes

How is C1q Deficiency Disorder Diagnosed?

C1q Deficiency Disorder is diagnosed on the basis of the following information:

• Physical examination of the individual and medical history evaluation
• Assessment of the presenting signs and symptoms
• Blood tests, as needed
• Dermoscopy: Dermoscopy is a diagnostic tool where a dermatologist examines the skin using a special magnified lens
• Wood’s lamp examination: In this procedure, the healthcare provider examines the skin using ultraviolet light. It is performed to examine the change in skin pigmentation
• Skin biopsy: A skin tissue biopsy is performed and sent to a laboratory for a pathological examination. The pathologist examines the biopsy under a microscope. After putting together clinical findings, special studies on tissues (if needed) and with microscope findings, the pathologist arrives at a definitive diagnosis
• Molecular genetic testing to check for or confirm specific causative gene mutation(s)
• Prenatal testing including abdominal ultrasound scans
• Diagnostic tests to check for an underlying disorder or condition if present

A differential diagnosis may be necessary to eliminate other conditions that present similar signs and symptoms.

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 C1q Deficiency Disorder?

The complications of C1q Deficiency Disorder may be severe and can include:

• Severe emotional stress
• Severe pain in joints
• Blood clots in the legs and lungs
• Uncontrolled blood pressure
• Pericardial effusion
• Pulmonary effusion
• Compromised function of kidneys including kidney failure
• Tissue and organ damage due to recurrent infections
• Decreased quality of life

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

How is C1q Deficiency Disorder Treated?

There is no cure for C1q Deficiency Disorder since it is a genetic condition. The treatment is usually given to manage the signs and symptoms and any complication that develops. This may include:

• Administration of medications
• Allogeneic hematopoietic stem cell transplantation
• Fresh frozen plasma (FFP) infusions
• In case of systemic lupus erythematosus, non-steroidal anti-inflammatory drugs (NSAIDs), corticosteroids, and immunosuppressive medications
• Glomerulonephritis treatment may involve lowering high blood pressure, maintaining fluid and electrolyte balance, use of diuretic pills, and regular urinary dialysis

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

How can C1q Deficiency Disorder be Prevented?

C1q 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

What is the Prognosis of C1q Deficiency Disorder? (Outcomes/Resolutions)

The prognosis of C1q Deficiency Disorder is dependent upon the severity of the signs and symptoms and associated complications, if any noted.

• Individuals with mild conditions have better prognosis than those with severe symptoms and complications. Typically, the prognosis may be assessed on a case-by-case basis
• In case of severe complications arising from kidney dysfunction, and involvement of other organs, such as the heart and lungs, the prognosis may be guarded

Additional and Relevant Useful Information for C1q Deficiency Disorder:

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

https://www.dovemed.com/healthy-living/skin-disorders/