Clinical and biochemical footprints of inherited metabolic diseases. XII. Immunological defects

Abstract

Immunological problems are increasingly acknowledged manifestations in many inherited metabolic diseases (IMDs), ranging from exaggerated inflammation, autoimmunity and abnormal cell counts to recurrent microbial infections. A subgroup of IMDs, the congenital disorders of glycosylation (CDG), includes CDG types that are even classified as primary immunodeficiencies. Here, we reviewed the list of metabolic disorders reported to be associated with various immunological defects and identified 171 IMDs accompanied by immunological manifestations. Most IMDs are accompanied by immune dysfunctions of which immunodeficiency and infections, innate immune defects, and autoimmunity are the most common abnormalities reported in 144/171 (84%), 44/171 (26%) and 33/171 (19%) of IMDs with immune system involvement, respectively, followed by autoinflammation 17/171 (10%). This article belongs to a series aiming at creating and maintaining a comprehensive list of clinical and metabolic differential diagnoses according to organ system involvement.

Keywords: Autoimmunity; Immune defect; Immunodeficiency; Inherited metabolic disorders.

Figure 1.

Occurrence (%) of symptoms associated with disorders affecting immune system in 10 categories of IMDs. The percentages for immunological involvement were calculated using as the denominator the total number of IMDs in each category presenting with any phenotype. Heat scale ranges from red (0%) for diseases with no particular symptoms reported to violet (100%) for diseases with particular symptoms occurring with highly frequency within the disorders group. For definition of 4 categories of disorders with immune system involvement see Supplemental Table 1.