Based on the dual role of H-protein in lipoylation of bioenergetic enzymes PDH and 2-KGDH, and its direct involvement in the GCS (Fig. 1), we would expect these pathogenic variants to result in clinical and biochemical symptoms generally similar to both PDH deficiency and NKH. The gene discussed is PDP1; the disease is pyruvate dehydrogenase E1-alpha deficiency.