*2.3. Patients*

Patient *MT-ND5*: During pregnancy aortic stenosis was diagnosed by sonography. The mother su ffered from epilepsy and was treated with Levetiracetam during pregnancy. On the first day of life, the girl presented with right ventricular hypertrophic cardiomyopathy. Sonography of the brain showed partial agenesis of the corpus callosum. At the age of 9 months and during an upper airway infection, the girl was admitted to intensive care because of apnea and insu fficient spontaneous breathing. In addition, a brain magnetic resonance imaging showed symmetric signal alterations in the basal ganglia and the brain stem. At the age of 91 2 months, the girl died from respiratory failure. Investigation of an unfrozen muscle biopsy revealed a decrease in CI: 20 nmol/min/mg protein (normal 28–76 nmol/min/mg protein, Table 1). Lactate was elevated in blood between 41–50 mg/dL (normal 6–22 mg/dL). Urine organic acid analysis revealed elevated lactate (262 mmol/mol creatinine), 3-hydroxybutyrate, and acetoacetate.

**Table 1.** Enzyme activities of oxidative phosphorylation (OXPHOS) complexes in muscle biopsies.


Clinical reference ranges are referred to a previous publication [31]. CS: citrate synthase, C: complex. Enzyme-specific activities were expressed as nanomoles of substrate per minute per milligram of protein (nmol/min/mg protein) and were normalized to the enzyme activity of CS. Indicated are ratios.

Patient *NDUFS1*: At the age of 7 months, this boy presented with muscular hypotonia. He lost skills such as head control and rolling over. Furthermore, he failed to thrive and lost body weight. A muscle biopsy was performed at the age of 9 months and showed decreased activity of respiratory chain CI: 20 nmol/min/mg protein (normal 28–76 nmol/min/mg protein, Table 1).
