The incidence and prevalence rates of hypogammaglobulinaemia are not clearly defined because the condition results from an extensive variety of primary and secondary defects. Primary hypogammaglobulinaemia is less common than secondary hypogammaglobulinaemia.[3]Onigbanjo M, Orange J, Perez E, et al. Hypogammaglobulinemia in a pediatric tertiary care setting. Clin Immunol. 2007 Oct;125(1):52-9.
http://www.ncbi.nlm.nih.gov/pubmed/17631052?tool=bestpractice.com
The estimates for prevalence of primary immunodeficiency (PID) and hypogammaglobulinaemia vary widely depending on the population studied. In 2007, reported estimates derived from US administrative healthcare databases ranged from 41.1 per 100,000 and 50.5 per 100,000 (publicly insured vs. privately insured persons, respectively).[4]Kobrynski L, Powell RW, Bowen S. Prevalence and morbidity of primary immunodeficiency diseases, United States 2001-2007. J Clin Immunol. 2014 Nov;34(8):954-61.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4820073
http://www.ncbi.nlm.nih.gov/pubmed/25257253?tool=bestpractice.com
Among hospitalised children in the US, the national prevalence of all PID diseases per 100,000 was 126.8 in 2012.[5]Rubin Z, Pappalardo A, Schwartz A, et al. Prevalence and outcomes of primary immunodeficiency in hospitalized children in the United States. J Allergy Clin Immunol Pract. 2018 Sep-Oct;6(5):1705-10;e1.
http://www.ncbi.nlm.nih.gov/pubmed/29339125?tool=bestpractice.com
However, not all of the defined PID diseases (>150) result in hypogammaglobulinaemia.
In the UK, the minimum prevalence of PID was 5.90 per 100,000 in 2017, with an average incidence between 1980 and 2000 of 7.6 cases per 100,000 UK live births.[6]Shillitoe B, Bangs C, Guzman D, et al. The United Kingdom Primary Immune Deficiency (UKPID) registry 2012 to 2017. Clin Exp Immunol. 2018 Jun;192(3):284-91.
http://www.ncbi.nlm.nih.gov/pubmed/29878323?tool=bestpractice.com
Predominantly antibody deficiencies are the most common form of PID, accounting for 77% of a PID registry survey.[7]Kirkpatrick P, Riminton S. Primary immunodeficiency diseases in Australia and New Zealand. J Clin Immunol. 2007 Sep;27(5):517-24.
http://www.ncbi.nlm.nih.gov/pubmed/17588141?tool=bestpractice.com
[8]Slade CA, Bosco JJ, Binh Giang T, et al. Delayed diagnosis and complications of predominantly antibody deficiencies in a cohort of Australian adults. Front Immunol. 2018 May 14;9:694.
https://www.frontiersin.org/articles/10.3389/fimmu.2018.00694/full
http://www.ncbi.nlm.nih.gov/pubmed/29867917?tool=bestpractice.com
Selective IgA deficiency is the most prevalent of these deficiencies (between 1/300 and 1/700), although the condition is often asymptomatic. Common variable immunodeficiency (CVID) affects around 1/30,000 and is the most clinically relevant antibody deficiency requiring immunoglobulin replacement therapy.[9]Bonilla FA, Khan DA, Ballas ZK, et al. Practice parameter for the diagnosis and management of primary immunodeficiency. J Allergy Clin Immunol. 2015 Nov;136(5):1186-205;e1-78.
https://www.jacionline.org/article/S0091-6749%2815%2900883-0/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/26371839?tool=bestpractice.com
[10]Conley ME, Notarangelo LD, Etzioni A. Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies). Clin Immunol. 1999 Dec;93(3):190-7.
http://www.ncbi.nlm.nih.gov/pubmed/10600329?tool=bestpractice.com
Newborn screening in 11 programmes in the US identified severe combined immunodeficiency (SCID) in 1 in 58,000 infants.[11]Kwan A, Abraham RS, Currier R, et al. Newborn screening for severe combined immunodeficiency in 11 screening programs in the United States. JAMA. 2014 Aug 20;312(7):729-38.
https://jamanetwork.com/journals/jama/fullarticle/1896983
http://www.ncbi.nlm.nih.gov/pubmed/25138334?tool=bestpractice.com
Hypogammaglobulinaemia can present at any age depending on the underlying cause. SCID presents early in infancy, whereas transient hypogammaglobulinaemia of infancy and X-linked agammaglobulinaemia (XLA) may present in early childhood when maternal IgG levels fall, or later in infancy. Common variable immunodeficiency (CVID) can have early or late onset but usually manifests in adolescence or early adulthood, although it may not be evident until patients are middle-aged or older.[12]Quinti I, Soresina A, Spadaro G, et al; Italian Primary Immunodeficiency Network. Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency. J Clin Immunol. 2007 May;27(3):308-16.
http://www.ncbi.nlm.nih.gov/pubmed/17510807?tool=bestpractice.com
[13]Wood P, Stanworth S, Burton J, et al. Recognition, clinical diagnosis and management of patients with primary antibody deficiencies: a systematic review. Clin Exp Immunol. 2007 Sep;149(3):410-23.
https://onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2249.2007.03432.x
http://www.ncbi.nlm.nih.gov/pubmed/17565605?tool=bestpractice.com
Reports suggest that most children with hypogammaglobulinaemia and PID have transient hypogammaglobulinaemia of infancy or CVID, while approximately 7% have SCID.[3]Onigbanjo M, Orange J, Perez E, et al. Hypogammaglobulinemia in a pediatric tertiary care setting. Clin Immunol. 2007 Oct;125(1):52-9.
http://www.ncbi.nlm.nih.gov/pubmed/17631052?tool=bestpractice.com
Most diseases that cause hypogammaglobulinaemia affect both sexes equally, although there are some rarer X-linked conditions (e.g., XLA). The prevalence of XLA in eastern and central European countries (total population 145,530,870) is estimated to be 1 per 1,399,000.[14]Tóth B, Volokha A, Mihas A, et al. Genetic and demographic features of X-linked agammaglobulinemia in Eastern and Central Europe: a cohort study. Mol Immunol. 2009 Jun;46(10):2140-6.
http://www.ncbi.nlm.nih.gov/pubmed/19419768?tool=bestpractice.com
Secondary hypogammaglobulinaemia related to myeloma and chronic lymphocytic leukaemia tends to present in older adults, >50 years of age.