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.

SyndromeGenePhenotype/immunologic phenotypeBernier criteria classification

Barth syndromeTafazzin (TAZ)3-Methylglutaconic aciduria, cardioskeletal myopathies/neutropeniaLikely affected

Omenn syndromeAdenylate kinase (AK) 2Inflammatory variant of leaky severe combined immunodeficiency (L-SCID)Unlikely affected

Cartilage Hair HypoplasiaMitochondrial RNA processing endoribonuclease (RMRP) Dwarfism/predisposition to infections, variable immune deficiency with T cell dysfunctionPossible