C1q deficiency

Autosomal recessive inherited C1q deficiency is a rare autosomal recessive disorder and is caused by a homozygous mutation in the C1QA(120550), C1QB (120570), or C1QC gene (120575), genes located on chromosome 1p36.

Clinically, the defect in C1QA is characterized by recurrent, often photosensitive skin lesions, chronic infections, and an increased risk of autoimmune diseases, particularly systemic lupus erythematosus (SLE) or SLE-like diseases. Also, C1q deficiency has been associated with chronic glomerulonephritis and renal failure. Functionally, C1q deficiency occurs in two distinct forms:

• Absence of C1q protein

or

• Presence of a dysfunctional molecule (Topaloglu et al. 1996 and Vassallo et al. 2007).

Thompson et al (1980) reported C1q deficiency in a 4-year-old son of Pakistani parents who presented with lupus-like disease and later developed glomerulonephritis. A younger sister, who was not yet clinically affected, had the same complement profile, and a younger brother had seminormal functional C1 levels.

Mampaso et al (1981) described 2 brothers and 1 sister from the Canary Islands who suffered from chronic light dermatosis (erythema, vesicles, hyperpigmentation, and atrophies). All 3 siblings had posterior capsular cataract. One patient suffered from alopecia areata. Furthermore, hematuria was detectable with normal renal function. Renal biopsies showed mesangial proliferative glomerulonephritis with deposition of immune complexes in all patients. Serum analysis showed a complete absence of C1q in the serum and the presence of various autoantibodies.

Hannema et al (1984) diagnosed 2 sisters and a brother with C1q deficiency (dysfunctional C1q molecule) at the age of 20 and 23 years, respectively, with a disease similar to systemic lupus erythematosus. One of the 2 sisters died. All 3 siblings suffered from glomerulonephritis in childhood. The brother was apparently healthy but had stage 1 membranous glomerulopathy on renal biopsy.

Topaloglu et al (1996) described 2 siblings with C1q deficiency and chronic light dermatosis. and during follow-up, one of them developed SLE with nephrotic syndrome. The other sibling had microscopic hematuria. Renal biopsies revealed mesangioproliferative glomerulonephritis in one child and IgA nephropathy in the other.

Topaloglu et al (1996) found that of 34 patients with C1q deficiency, all but one had SLE or SLE-like disease.

Marquart et al (2007) described 3 affected sisters from an Inuit family with C1Q deficiency. All 3 suffered from SLE-like skin disease. 2 had episodes of pneumonia and septicemia; none had renal involvement.

Schejbel et al (2011) reported on a 10-year-old boy with C1q deficiency and systemic lupus erythematosus. His initial symptoms were malaria, discoid lupus erythematosus, oral ulceration. Furthermore, the authors described two Sudanese siblings, aged 4 and 10 years, with C1q deficiency and SLE, whose earlier diagnoses were cutaneous lupus, bacterial meningitis, and bacterial keratitis. No renal involvement.

Higuchi et al. (2013) reported a four-year-old Japanese girl with C1q deficiency who had fever, facial erythema, joint pain, and oral ulceration for three months. She was diagnosed with discoid lupus erythematosus. Total complement activity (CH50) was undetectable, and C3 and C4 levels were normal.

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