Symptoma

Transient Hypogammaglobulinemia of Infancy

Immunoglob Maturational Delay

Transient hypogammaglobulinemia of infancy is defined differently by various authors. Some consider low immunoglobulin (IgG and IgA) necessary in order to establish this diagnosis, while others argue that only a reduction in IgG level is needed or that any type of immunoglobulin (A, G or M) can be decreased in this condition. Hyper-IgM syndrome and common variable immunodeficiency are also included in the definition of transient hypogammaglobulinemia of infancy by some researchers, but not aberrations of cellular immunity. Immunological abnormalities must resolve by the age of 4 years. Vaccination response must be normal or slightly diminished.

Transient hypogammaglobulinemia of infancy usually becomes symptomatic between 6 and 12 months of age [1] and is characterized by frequent upper respiratory and sometimes other types of infections: gastrointestinal, urinary or invasive [2] [3]. These consist of episodes of otitis, sinusitis, bronchitis, rhinopharyngitis, or, in rare cases, meningitis [4], severe varicella [5] or oral candidiasis. Lower respiratory tract infections are also encountered [5]. Allergic manifestations coexist in about half of the cases [1]: eczema, food allergy or intolerance [6], asthma and allergic rhinitis [7]. Seldom, patients are asymptomatic [8]. Gastrointestinal symptoms include chronic diarrhea and recurrent vomiting. Infections usually become less frequent after the patients turn 3 years old.

Clinical examination reveals normal sized or hypertrophic tonsils, adenoids or lymph nodes. Splenomegaly is present in approximately 25% of patients, more often in those with hyper-IgM syndrome. Lymphoid tissue is hyperplastic in intrinsic B-cell immune defects, which aids clinical differential diagnosis.

  • Turkish

    In this study, we analysed the B cell subsets of patients with an initial THI diagnosis (n 20) and compared them with those of healthy age-matched Turkish children (n 72). [ncbi.nlm.nih.gov]

    O'Donnell B. 2012 12 The number of circulating CD4 CD25high Foxp3 T lymphocytes is transiently elevated in the early childhood of transient hypogammaglobulinemia of infancy patients. ( 21531630 ) Rutkowska M....Siedlar M. 2011 13 New laboratory findings in Turkish [malacards.org]

    New laboratory findings in Turkish patients with transient hypogammaglobulinemia of infancy. Iran J Allergy Asthma Immunol. 2010 December. 9(4):237-243. [Medline]. Van Winkle RC, Hauck WW, McGeady SJ. [emedicine.medscape.com]

    […] clinical features FMF TRAPS HIDS FCAS MWS NOMID/CINCA usual ethnicity Turkish, Armenian, Arab, Jewish, Italian any ethnicity Dutch, other Northern European mostly European mostly European any ethnicity duration of attacks 12-72 hours days to weeks 3-7 [ufrgs.br]

  • Diarrhea

    Gastrointestinal symptoms include chronic diarrhea and recurrent vomiting. Infections usually become less frequent after the patients turn 3 years old. Clinical examination reveals normal sized or hypertrophic tonsils, adenoids or lymph nodes. [symptoma.com]

    Gastrointestinal symptoms may include chronic diarrhea, persistent vomiting, food allergy and/or intolerance. Neutropenia (low white blood cells) is not uncommon. [primaryimmune.org]

    Italian any ethnicity Dutch, other Northern European mostly European mostly European any ethnicity duration of attacks 12-72 hours days to weeks 3-7 days 12-24 hours 2-3 days continuous, with flares abdominal sterile peritonitis, constipation peritonitis, diarrhea [ufrgs.br]

    Diarrhea, failure to thrive, opportunistic infections, and severe routine infections in a child younger than three months should raise suspicion for SCID. [aafp.org]

    chronic diarrhea due to giardiasis, persistent discharging ears or chronic sinusitis due to encapsulated organisms Uncommon Infections Deep seated skin or organ abscesses (usually associated with neutropenia in XLA or Hyper IgM syndrome) Pneumocystis [indianpediatrics.net]

  • Chronic Diarrhea

    Gastrointestinal symptoms include chronic diarrhea and recurrent vomiting. Infections usually become less frequent after the patients turn 3 years old. Clinical examination reveals normal sized or hypertrophic tonsils, adenoids or lymph nodes. [symptoma.com]

    Gastrointestinal symptoms may include chronic diarrhea, persistent vomiting, food allergy and/or intolerance. Neutropenia (low white blood cells) is not uncommon. [primaryimmune.org]

    diarrhea or chronic lung disease. [indianpediatrics.net]

  • Recurrent Vomiting

    Gastrointestinal symptoms include chronic diarrhea and recurrent vomiting. Infections usually become less frequent after the patients turn 3 years old. Clinical examination reveals normal sized or hypertrophic tonsils, adenoids or lymph nodes. [symptoma.com]

  • Persistent Vomiting

    Gastrointestinal symptoms may include chronic diarrhea, persistent vomiting, food allergy and/or intolerance. Neutropenia (low white blood cells) is not uncommon. [primaryimmune.org]

Transient hypergammaglobulinemia of infancy is characterized by certain laboratory hallmarks. Immunoglobulin G is two standard deviations below the mean value on at least two different occasions. Immunoglobulins A and M may also be diminished, but this is not a necessary trait. These abnormalities must resolve during childhood, for the "transient" term to apply. Antibody formation after infection or vaccination (both protein and polysaccharide [9] antigens) is normal [7], but may not persist over time [10]. Others argue that response to polysaccharide antigens may be diminished [11]. In permanent forms of hypogammaglobulinemia, antibody response to vaccine is insufficient.

Cellular immunity is usually not compromised. Memory B lymphocytes and class-switched B cells are normal [12] or decreased [13], while CD4 +CD25 highFoxP3 + T-regulatory (Treg) may be increased. Mitogen response is normal [14]. Immunoglobulin G formation can be impaired [15] or normal [16]. Some authors have also described patients with associated abnormalities, such as transient or permanent neutropenia or acute lymphoblastic leukemia. CD3+ and especially CD4+ T cells are often normal but may be decreased, while CD19+ B cell number may be increased. Lymphoproliferative responses are normal in vitro.

Other useful laboratory workup methods include determination of CD3+, CD4+, CD8+ T-cell percentages using flow cytometry and testing T cell function. This can be done by skin testing for antigens like Candida albicans and tetanus toxoid and by assessing lymphoproliferative responses to mitogens.

Infections may be diagnosed using a complete cell blood count and various imaging methods, like chest or sinus radiography or computed tomography.

  1. Whelan MA, Hwan WH, Beausoleil J, et al. Infants presenting with recurrent infections and low immunoglobulins: characteristics and analysis of normalization. J Clin Immunol. 2006;26(1):7-11.
  2. Kutukculer N, Gulez N. The outcome of patients with unclassified hypogammaglobulinemia in early childhood. Pediatr Allergy Immunol. 2009; 20:693.
  3. Artac H, Kara R, Gokturk B, et al. Reduced CD19 expression and decreased memory B cell numbers in transient hypogammaglobulinemia of infancy. Clin Exp Med. 2013; 13:257.
  4. Qian JH, Zhu JX, Zhu XD, et al. Clinical features and follow-up of Chinese patients with symptomatic hypogammaglobulinemia in infancy. Chin Med J (Engl). 2009; 122:1877.
  5. Dalal I, Reid B, Nisbet-Brown E, et al. The outcome of patients with hypogammaglobulinemia in infancy and early childhood. J Pediatr. 1998; 133:144.
  6. Fineman SM, Rosen FS, Geha RS. Transient hypogammaglobulinemia, elevated immunoglobulin E levels, and food allergy. J Allergy Clin Immunol. 1979; 64:216.
  7. Dorsey MJ, Orange JS. Impaired specific antibody response and increased B-cell population in transient hypogammaglobulinemia of infancy. Ann Allergy Asthma Immunol. 2006;97(5):590-595.
  8. Tiller TL Jr, Buckley RH. Transient hypogammaglobulinemia of infancy: review of the literature, clinical and immunologic features of 11 new cases, and long-term follow-up. J Pediatr. 1978; 92:347.
  9. Kiliç SS, Tezcan I, Sanal O, et al. Transient hypogammaglobulinemia of infancy: clinical and immunologic features of 40 new cases. Pediatr Int. 2000;42:647.
  10. Dalal I, Roifman CM. Hypogammaglobulinemia of infancy. Immunol Allergy Clin North Am. 2001;21:129-139.
  11. Wolpert J, Knutsen AP. Natural history of selective antibody deficiency to bacterial polysaccharide antigens in children. Pediatr Asthma, Allergy, Immunol. 1998;12:183-191.
  12. Kowalczyk D, Mytar B, Zembala M. Cytokine production in transient hypogammaglobulinemia and isolated IgA deficiency. J Allergy Clin Immunol. 1997;100:556.
  13. Bukowska-Strakova K, Kowalczyk D, Baran J, et al. The B-cell compartment in the peripheral blood of children with different types of primary immunodeficiency. Pediatr Res. 2009;66:28-34.
  14. Dressler F, Peter HH, Müller W, et al. Transient hypogammaglobulinemia of infancy: Five new cases, review of the literature and redefinition. Acta Paediatr Scand. 1989;78:767.
  15. Moschese V, Graziani S, Avanzini MA, et al. A prospective study on children with initial diagnosis of transient hypogammaglobulinemia of infancy: results from the Italian Primary Immunodeficiency Network. Int J Immunopathol Pharmacol. 2008;21:343.