Leigh syndrome in individuals bearing m.9185T>C MTATP6 variant. Is hyperventilation a factor which starts its development?

Leigh syndrome (LS), subacute necrotizing encephalomyelopathy is caused by various genetic defects, including m.9185T>C MTATP6 variant. Mechanism of LS development remains unknown. We report on the acid-base status of three patients with m.9185T>C related LS. At the onset, it showed respiratory alkalosis, reflecting excessive respiration effort (hyperventilation with low pCO2). In patient 1, the deterioration occurred in temporal relation to passive oxygen therapy. To the contrary, on the recovery, she demonstrated a relatively low respiratory drive, suggesting that a "hypoventilation" might be beneficial for m.9185T>C carriers. As long as circumstances of the development of LS have not been fully explained, we recommend to counteract hyperventilation and carefully dose oxygen in patients with m.9185T>C related LS.

Comparison of Granulomatosis with Polyangiitis Clinical Features in Patients Depending on Involvement or Absence of Kidney Involvement.

BACKGROUND: GPA is necrotizing inflammation of the small vessels with granulomas. Kidney involvement deteriorated its prognosis. OBJECTIVE: Comparison of GPA patients with Kidney (KI) and without Kidney Involvement (nKI). MATERIALS AND METHODS: We conducted a cross-sectional study of 50 consecutive adult GPA patients, 25 KI from Nephrology and 25 nKI from the Rheumatology Department of Central Clinical Hospital Ministry of Interior in Warsaw. We analyzed clinical features, organ involvement, laboratory, serological, imaging, histopathological data, BVAS and treatment. RESULTS: The mean age of KI patients was statistically older than nKI (67.3±9.5 vs. 55.1±15.9, p=0.002). Generalized, severe, disease resistance was observed respectively in 92% vs. 44%, p<0.001. The number of red blood cells (3.47 vs. 4.41T/l, p<0.001), hemoglobin (10.0 vs. 12.9 g/dl, p<0.001) was lower in KI, higher mean serum creatinine (3.95 vs. 0.89 mg/dl, p<0.001), lower GFR (20.1 vs. 79.3, p<0.001), higher CRP (median: 43.4 vs. 2.0 mg/l, p<0.001), BVAS (16.6±4.4 vs. 10.1±6.2, p<0.001), c-ANCA (median: 119.0 vs. 15.2CU, p=0.017). Nodules in 28% KI, in 4% nKI (p=0.048) in chest X-ray, infiltration in 43.5% KI, in 15% nKI (p=0.042) in HRCT were observed. Skin granulomas were found in 61.5% nKI vs. 18.2% KI, (p=0.047). Renal biopsy revealed in KI patients focal segmental glomerulonephritis in 11.8%, crescentic glomerulonephritis in 17.6%, and pauci-immune crescentic glomerulonephritis in 70.6%. CONCLUSION: In patients with KI we found generalized, severe, resistant GPA, higher BVAS more frequently than inpatients without KI. The results of laboratory parameters were worse in patients with KI. Aggressive immunosuppressive treatment is often used in the KI group.