Síndrome hemolítico urémico incompleto asociado a déficit parcial de factor H

Olaciregui Echenique, I.; Areses Trapote, R.; Ubetagoyena Arrieta, M.; Sota Busselo, I.; García Pardos, C.; Echaniz Aizpuru, P.

doi:10.1157/13098939

Anales de Pediatría (English Edition)

ISSN: 2341-2879

The Spanish Pediatric Association (Asociación Española de Pediatría, AEP) has as one of its main objectives the dissemination of rigorous and up-to-date scientific information on the various areas of pediatrics. Annals of Pediatrics is an open access journal that serves as the Association's Scientific Expression Organ and constitutes the vehicle through which members communicate. Annals of Pediatrics publishes, in English and Spanish, original research papers on pediatrics, as well as review articles prepared by experts in each specialty, and guidelines or positioning documents prepared by the different Societies/Specialized Sections integrated into the Spanish Pediatric Association. The journal, a reference for Spanish-speaking pediatrics, is indexed in the most important international databases: Index Medicus/Medline IBECS, IME, SCOPUS, Science Citation Index Expanded, Journal Citations Report, Embase/Excerpta Medica, Directory of Open Access Journals (DOAJ).

Indexed in:

Index Medicus/Medline IBECS, IME, SCOPUS, Science Citation Index Expanded, Journal Citations Report, Embase/Excerpta Medica, Directory of Open Access Journals (DOAJ)

El síndrome hemolítico urémico (SHU) asocia anemia hemolítica, trombocitopenia e insuficiencia renal. La mayoría de los casos están relacionados con las toxinas (verotoxinas) producidas por Escherichia coli 0157:H7 y generalmente tienen un buen pronóstico renal. Existen formas atípicas, con peor pronóstico, que pueden ser secundarias, entre otras causas, a mutaciones en el gen codificador del factor H, proteína que regula la activación de la vía alternativa del complemento. Su déficit, produce una activación continua del complemento, dañando las células endoteliales de los capilares.

Presentamos un caso clínico de SHU incompleto (ausencia de plaquetopenia y uremia) y atípico en el que se detectó una hipocomplementemia secundaria a un déficit parcial de factor H, cuya evolución fue favorable. Previo al inicio de los síntomas, el paciente presentó una infección por Campylobacter que actuó como agente precipitante del cuadro. El análisis genético demostró una mutación en heterocigosis (C846T) localizada en el dominio SCR4 que genera un cambio de aminoácido en la molécula del factor H (Pro240Leu). Es posible que dicha mutación haya sido la causante del déficit parcial del factor H y del cuadro que presentó al ingreso.

Palabras clave:

Síndrome hemolítico urémico

Síndrome hemolítico urémico incompleto

Síndrome hemolítico urémico atípico

Factor H

Campylobacter jejuni

Hemolytic uremic syndrome (HUS) consists of the association of hemolytic anemia, thrombocytopenia and renal failure. Most cases are related to toxins (verotoxins) produced by Escherichia coli 0157:H7 and generally have good renal prognosis. Atypical forms can occur, with a less favorable prognosis, and can be due to mutations in the gene codifying factor H, a protein that regulates activation of the alternative complement pathway, among other causes. Factor H deficiency produces continuous complement activation, causing injury to capillary endothelial cells.

We report a case of incomplete (absence of thrombocytopenia and uremia), atypical HUS in which hypocomplementemia secondary to partial factor H deficiency was detected, with favorable outcome. Prior to symptom onset, the patient had a Campylobacter infection, precipitating the symptoms. Genetic analysis showed a heterozygous mutation (C846T) located in the SCR4 domain, generating an amino acid change in the factor H molecule (Pro240Leu). This mutation may have been the cause of the partial factor H deficiency and the patient's symptoms on admission.

Key words:

Hemolytic uremic syndrome

Incomplete hemolytic uremic syndrome

Atypical hemolytic uremic syndrome

Factor H

Campylobacter jejuni

Full text is only aviable in PDF

Bibliografía

[1.]

R. Siegler, R. Oakes.

Hemolytic uremic syndrome; pathogenesis, treatment, and outcome.

Curr Opin Pediatr., 17 (2005), pp. 200-204

Medline

[2.]

P.E. Ray, X.H. Liu.

Pathogenesis of Shiga toxin-induced hemolytic uremic syndrome.

Pediatr Nephrol., 16 (2001), pp. 823-839

Medline

[3.]

P. Mariani-Kurkdjian, E. Bingen.

Hemolytic-uremic syndrome after verotoxin-producing Escherichia coli infection.

Presse Med., 24 (1995), pp. 99-101

Medline

[4.]

G. Filler, S. Radhakrishnan, L. Strain, A. Hill, G. Knoll, T.H. Goodship.

Challenges in the management of infantile factor H associated hemolytic uremic syndrome.

Pediatr Nephrol., 19 (2004), pp. 908-911

http://dx.doi.org/10.1007/s00467-004-1526-9 | Medline

[5.]

C. Licht, A. Weyersberg, S. Heinen, L. Stapenhorst, J. Devenge, B. Beck, et al.

Successful plasma therapy for atypical hemolytic uremic syndrome caused by factor H deficiency owing to a novel mutation in the complement cofactor protein domain 15.

Am J Kidney Dis., 45 (2005), pp. 415-421

Medline

[6.]

P. Sánchez-Corral, D. Pérez-Caballero, O. Huarte, A.M. Simckes, E. Goicoechea, M. López-Trascasa, et al.

Structural and functional characterization of factor H mutations associated with atypical hemolytic uremic syndrome.

Am J Hum Genet., 71 (2002), pp. 1285-1295

http://dx.doi.org/10.1086/344515 | Medline

[7.]

S. Rodríguez de Córdoba, J. Esparza-Gordillo, E. Goicoechea de Jorge, M. López-Trascasa, P. Sánchez-Corral.

The human complement factor H: functional roles, genetic variations and disease associations.

Mol Immunol., 41 (2004), pp. 355-367

http://dx.doi.org/10.1016/j.molimm.2004.02.005 | Medline

[8.]

H.P.H. Neumann, M. Salzmann, B. Bohnert-Iwan, T. Mannuelian, C. Skerka, D. Lenk, et al.

Haemolytic uraemic syndrome and mutations of the factor H gene: A registry-based study of German speaking countries.

J Med Genet., 40 (2003), pp. 676-681

Medline

[9.]

A.K. Sharma, M.K. Pangburn.

Identification of three physically and functionally distinct binding sites for C3b in human complement factor H by deletion mutagenesis.

Proc Natl Acad Sci U S A, 93 (1996), pp. 10996-11001

Medline

[10.]

M.K. Pangburn, K.L.W. Pangburn, V. Koistinen, S. Meri, A.K. Sharma.

Molecular mechanisms of target recognition in an innate immune system: interactions among factor H, C3b, and target in the alternative pathway of human complement.

J Immunol., 164 (2000), pp. 4742-4751

Medline

[11.]

M.A. Dragon-Durey, V. Frémeaux-Bacchi, C. Loirat, J. Blouin, P. Niaudet, G. Deschenes, et al.

Heterozygous and homozygous factor H deficiencies associated with hemolytic uremic syndrome or membranoproliferative glomerulonephritis: Report and genetic analysis of 16 cases.

J Am Soc Nephrol., 15 (2004), pp. 787-795

Medline

[12.]

D. Landau, H. Shalev, G. Levy-Finer, A. Polonsky, Y. Segev, L. Katchko.

Familial hemolytic uremic syndrome associated with complement Factor H deficiency.

J Pediatr., 138 (2001), pp. 412-417

http://dx.doi.org/10.1067/mpd.2001.112649 | Medline