The incidence and prevalence rates of hypogammaglobulinemia are not clearly defined because the condition results from an extensive variety of primary and secondary defects. Primary hypogammaglobulinemia is less common than secondary hypogammaglobulinemia.[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 hypogammaglobulinemia 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 hospitalized 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 hypogammaglobulinemia.
Predominantly antibody deficiencies are the most common form of PID, accounting for 77% of a PID registry survey.[6]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
[7]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. About 30 out of 100,000 people have common variable immunodeficiency in the US and it is the most clinically relevant antibody deficiency requiring immunoglobulin replacement therapy.[7]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
[8]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
[9]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 programs in the US identified severe combined immunodeficiency (SCID) in 1 in 58,000 infants.[10]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
Hypogammaglobulinemia can present at any age depending on the underlying cause. SCID presents early in infancy, whereas transient hypogammaglobulinemia of infancy and X-linked agammaglobulinemia (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.[11]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
[12]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 hypogammaglobulinemia and PID have transient hypogammaglobulinemia 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 hypogammaglobulinemia affect both sexes equally, although there are some rarer X-linked conditions (e.g., XLA). Secondary hypogammaglobulinemia related to myeloma and chronic lymphocytic leukemia tends to present in older adults, ages >50 years.