# 613912

COMPLEMENT FACTOR D DEFICIENCY; CFDD


Alternative titles; symbols

FACTOR D DEFICIENCY


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
19p13.3 Complement factor D deficiency 613912 AR 3 CFD 134350
Clinical Synopsis
 

INHERITANCE
- Autosomal recessive
IMMUNOLOGY
- Increased susceptibility to bacterial infections
- Increased susceptibility to Neisseria infection
LABORATORY ABNORMALITIES
- Decreased complement factor D
- Decreased activity of complement factor D
MISCELLANEOUS
- Variable severity
MOLECULAR BASIS
- Caused by mutation in the complement factor D gene (CFD, 134350.0001)

TEXT

A number sign (#) is used with this entry because complement factor D deficiency (CFDD) is caused by homozygous mutation in the CFD gene (134350) on chromosome 19p13.


Description

Complement factor D deficiency is an autosomal recessive immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway (summary by Biesma et al., 2001).


Clinical Features

Kluin-Nelemans et al. (1984) described a partial functional deficiency of factor D in 2 Dutch adult monozygous female twins with recurrent bacterial respiratory infections since childhood.

Hiemstra et al. (1989) reported a 24-year-old Dutch man with recurrent Neisseria infections. Laboratory studies found no detectable serum complement factor D hemolytic activity, and absence of measurable amounts of factor D antigen. Addition of purified factor D to the patient's serum restored full activity of the alternative complement pathway. The sister and the father, as well as the parents of the mother, had factor D levels within the normal range; the factor D level of the mother was decreased.

Biesma et al. (2001) reported a 23-year-old Dutch woman, born of consanguineous parents, with septic shock due to Neisseria meningitidis in blood and cerebrospinal fluid. A deceased family member had a history of recurrent bacterial meningitis. Laboratory studies showed absence of factor D activity in the proband. However, absence of factor D activity was also found in 3 family members who did not have a history of recurrent infections. Combined with the earlier observation of Hiemstra et al. (1989), this finding suggested that factor D deficiency predisposes to invasive meningococcal disease. None of the reported patients was obese.

Sprong et al. (2006) reported a Turkish brother and sister with invasive meningococcal disease. The 19-month-old girl was admitted with purpura, high fever, coughing, diarrhea, and vomiting. Cerebrospinal fluid cultures grew N. meningitidis. She died in refractory shock about 47 hours after hospital admission. Four years later, the 13-month-old brother was admitted to the same hospital because of sudden onset of fever and a petechial rash. At the age of 4 months, he had been hospitalized for a respiratory syncytial virus infection complicated by bacterial superinfection. Blood cultures grew N. meningitidis. Immunologic studies indicated that factor D was undetectable. Because of this deficiency, the boy was put on antibiotic prophylaxis and was vaccinated for N. meningitidis.


Inheritance

Complement factor D deficiency is inherited in an autosomal recessive pattern (Biesma et al., 2001).


Molecular Genetics

In a Dutch family with factor D deficiency, Biesma et al. (2001) identified a homozygous mutation in the CFD gene (134350.0001).

In 2 children of a Turkish family with N. meningitis due to complement factor D deficiency, Sprong et al. (2006) identified a homozygous mutation in the factor D gene (134350.0002).


REFERENCES

  1. Biesma, D. H., Hannema, A. J., van Velzen-Blad, H., Mulder, L., van Zwieten, R., Kluijt, I., Roos, D. A family with complement factor D deficiency. J. Clin. Invest. 108: 233-240, 2001. [PubMed: 11457876, images, related citations] [Full Text]

  2. Hiemstra, P. S., Langeler, E., Compier, B., Keepers, Y., Leijh, P. C. J., van den Barselaar, M. T., Overbosch, D., Daha, M. R. Complete and partial deficiencies of complement factor D in a Dutch family. J. Clin. Invest. 84: 1957-1961, 1989. [PubMed: 2687330, related citations] [Full Text]

  3. Kluin-Nelemans, H. C., van Velzen-Blad, H., van Helden, H. P. T., Daha, M. R. Functional deficiency of complement factor D in monozygous twin. Clin. Exp. Immun. 58: 724-730, 1984. [PubMed: 6568950, related citations]

  4. Sprong, T., Roos, D., Weemaes, C., Neeleman, C., Geesing, C. L. M., Mollnes, T. E., van Deuren, M. Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections. Blood 107: 4865-4870, 2006. [PubMed: 16527897, related citations] [Full Text]


Creation Date:
Cassandra L. Kniffin : 4/19/2011
carol : 12/12/2011
terry : 4/21/2011
carol : 4/20/2011
ckniffin : 4/20/2011

# 613912

COMPLEMENT FACTOR D DEFICIENCY; CFDD


Alternative titles; symbols

FACTOR D DEFICIENCY


SNOMEDCT: 234607008;   ORPHA: 169467;  


Phenotype-Gene Relationships

Location Phenotype Phenotype
MIM number
Inheritance Phenotype
mapping key
Gene/Locus Gene/Locus
MIM number
19p13.3 Complement factor D deficiency 613912 Autosomal recessive 3 CFD 134350

TEXT

A number sign (#) is used with this entry because complement factor D deficiency (CFDD) is caused by homozygous mutation in the CFD gene (134350) on chromosome 19p13.


Description

Complement factor D deficiency is an autosomal recessive immunologic disorder characterized by increased susceptibility to bacterial infections, particularly Neisseria infections, due to a defect in the alternative complement pathway (summary by Biesma et al., 2001).


Clinical Features

Kluin-Nelemans et al. (1984) described a partial functional deficiency of factor D in 2 Dutch adult monozygous female twins with recurrent bacterial respiratory infections since childhood.

Hiemstra et al. (1989) reported a 24-year-old Dutch man with recurrent Neisseria infections. Laboratory studies found no detectable serum complement factor D hemolytic activity, and absence of measurable amounts of factor D antigen. Addition of purified factor D to the patient's serum restored full activity of the alternative complement pathway. The sister and the father, as well as the parents of the mother, had factor D levels within the normal range; the factor D level of the mother was decreased.

Biesma et al. (2001) reported a 23-year-old Dutch woman, born of consanguineous parents, with septic shock due to Neisseria meningitidis in blood and cerebrospinal fluid. A deceased family member had a history of recurrent bacterial meningitis. Laboratory studies showed absence of factor D activity in the proband. However, absence of factor D activity was also found in 3 family members who did not have a history of recurrent infections. Combined with the earlier observation of Hiemstra et al. (1989), this finding suggested that factor D deficiency predisposes to invasive meningococcal disease. None of the reported patients was obese.

Sprong et al. (2006) reported a Turkish brother and sister with invasive meningococcal disease. The 19-month-old girl was admitted with purpura, high fever, coughing, diarrhea, and vomiting. Cerebrospinal fluid cultures grew N. meningitidis. She died in refractory shock about 47 hours after hospital admission. Four years later, the 13-month-old brother was admitted to the same hospital because of sudden onset of fever and a petechial rash. At the age of 4 months, he had been hospitalized for a respiratory syncytial virus infection complicated by bacterial superinfection. Blood cultures grew N. meningitidis. Immunologic studies indicated that factor D was undetectable. Because of this deficiency, the boy was put on antibiotic prophylaxis and was vaccinated for N. meningitidis.


Inheritance

Complement factor D deficiency is inherited in an autosomal recessive pattern (Biesma et al., 2001).


Molecular Genetics

In a Dutch family with factor D deficiency, Biesma et al. (2001) identified a homozygous mutation in the CFD gene (134350.0001).

In 2 children of a Turkish family with N. meningitis due to complement factor D deficiency, Sprong et al. (2006) identified a homozygous mutation in the factor D gene (134350.0002).


REFERENCES

  1. Biesma, D. H., Hannema, A. J., van Velzen-Blad, H., Mulder, L., van Zwieten, R., Kluijt, I., Roos, D. A family with complement factor D deficiency. J. Clin. Invest. 108: 233-240, 2001. [PubMed: 11457876] [Full Text: https://doi.org/10.1172/JCI12023]

  2. Hiemstra, P. S., Langeler, E., Compier, B., Keepers, Y., Leijh, P. C. J., van den Barselaar, M. T., Overbosch, D., Daha, M. R. Complete and partial deficiencies of complement factor D in a Dutch family. J. Clin. Invest. 84: 1957-1961, 1989. [PubMed: 2687330] [Full Text: https://doi.org/10.1172/JCI114384]

  3. Kluin-Nelemans, H. C., van Velzen-Blad, H., van Helden, H. P. T., Daha, M. R. Functional deficiency of complement factor D in monozygous twin. Clin. Exp. Immun. 58: 724-730, 1984. [PubMed: 6568950]

  4. Sprong, T., Roos, D., Weemaes, C., Neeleman, C., Geesing, C. L. M., Mollnes, T. E., van Deuren, M. Deficient alternative complement pathway activation due to factor D deficiency by 2 novel mutations in the complement factor D gene in a family with meningococcal infections. Blood 107: 4865-4870, 2006. [PubMed: 16527897] [Full Text: https://doi.org/10.1182/blood-2005-07-2820]


Creation Date:
Cassandra L. Kniffin : 4/19/2011

Edit History:
carol : 12/12/2011
terry : 4/21/2011
carol : 4/20/2011
ckniffin : 4/20/2011