Powering the Immune System: Mitochondria in Immune Function and Deficiency

Table 1

Primary mitochondrial disorders are recognized as a group of multisystem disorders with various features and supporting laboratory findings [62]. Genetic or metabolic diagnoses—when identifiable—arise from perturbations of gene products localizing to the mitochondrion that may be nuclear or mitochondrially encoded [9] and are not necessary for a clinical diagnosis. The immunodeficiencies above have not typically been described as primary mitochondrial disorders but are linked to genetic defects of genes localizing to the mitochondrion. While published cases of Barth syndrome and Cartilage Hair Hypoplasia would be scored as “possible” or “likely affected” based on criteria by Bernier and colleagues, published cases of Omenn syndrome score as “unlikely affected” by a primary mitochondrial disorder.

Syndrome	Gene	Phenotype/immunologic phenotype	Bernier criteria classification
Barth syndrome	Tafazzin (TAZ)	3-Methylglutaconic aciduria, cardioskeletal myopathies/neutropenia	Likely affected
Omenn syndrome	Adenylate kinase (AK) 2	Inflammatory variant of leaky severe combined immunodeficiency (L-SCID)	Unlikely affected
Cartilage Hair Hypoplasia	Mitochondrial RNA processing endoribonuclease (RMRP)	Dwarfism/predisposition to infections, variable immune deficiency with T cell dysfunction	Possible