From: Impact of cardiovascular involvement on the clinical course of paediatric mitochondrial disorders
 | Overall | Patients without CVI | Patients with CVI | p-value |
---|---|---|---|---|
Number of patients (%) | 86 | 55 (64%) | 31 (36%) | Â |
Males/Females | 0.5 | 0.15 | 1.8 | < 0.01 |
Mean age at diagnosis (years; ±SDS) | 6.4 (±8.58) | 7.8 (±10.08) | 5.75 (±7.67) | 0.3 |
Mean age at LFUP (years; ±SDS) | 11.4 (±10.1) | 11.8 (±9.17) | 10.98 (±11.5) | 0.7 |
Muscular biopsy (n° patients; %) | 55 (63.9%) | 37 (67.2%) | 18 (58%) | 0.4 |
Respiratory chain enzyme deficiency (n°;%) | 49 (57%) | 35 (63.6%) | 14 (45%) |  |
- Complex I | 12 (14%) | 9 (16.3%) | 3 (9.7%) | 0.7 |
- Complex II | 1 (1.2%) | 1 (1.8%) | – | 0.5 |
- Complex III | 2 (2.3%) | 2 (3.6%) | – | 0.4 |
- Complex IV | 3 (3.5%) | 2 (3.6%) | 1 (3.2%) | 0.8 |
- Complex V | 4 (4.6%) | 2 (3.6%) | 2 (6.4%) | 0.3 |
- Combined deficiencies | 27 (31.4%) | 19 (34.5%) | 8 (25.8%) | 0.8 |
Molecular analysis (n°;%) | 57 (66.3%) | 31 (56.3%) | 26 (83.8%) |  |
- MTTL1 (A3243G) | 8 (9.3%) | 3 (5.4%) | 5 (16.1%) | 0.4 |
- TMEM70 | 5 (5.8%) | – | 5 (16.1%) | < 0.01 |
- NARP | 4 (4.6%) | 3 (5.4%) | 1 (3.2%) | 0.4 |
- Barth syndrome | 4 (4.6%) | – | 4 (12.9%) | 0.02 |
- POLG | 2 (2.3%) | 2 (3.6%) | – | 0.4 |
- ACAD9 | 2 (2.3%) | 1 (1.8%) | 1 (3.2%) | 0.4 |
- SURF1 | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- NDFUS1 | 1 (1.2%) | – | 1 (3.2%) | 0.8 |
- SDHB | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- ELAC2 | 1 (1.2%) | – | 1 (3.2%) | 0.4 |
- DGUOK | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- TK2 | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- tRNA (Glu) | 1 (1.2%) | – | 1 (1.2%) | 0.4 |
- NAHD dehydrogenase (complex I) subunits: | 7 (8.1%) | 5 (9%) | 2 (6.5%) | 0.07 |
o MTND1 | 2 (2.3%) | 1 (1.8%) | 1 (3.2%) | Â |
o MTND2 | 1 (1.2%) | 1 (1.8%) | – |  |
o MTND3 | 1 (1.2%) | – | 1 (3.2%) |  |
o MTND5 | 1 (1.2%) | 1 (1.8%) | – |  |
o MTND6 | 2 (2.3%) | 2 (3.6%) | – |  |
- MTCYB1 | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- MT-CO1 | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- MT-TC | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- Leber’s hereditary optic neuropathy | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- Kearns-Sayre disease | 2 (2.3%) | 1 (1.8%) | 1 (3.2%) | 0.8 |
- Sengers disease | 1 (1.2%) | – | 1 (3.2%) | 0.2 |
- Large mt-DNA depletion | 2 (2.3%) | 1 (1.8%) | 1 (3.2%) | 0.8 |
- TIMMDC1 | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- NUBPL | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- SFXN4 | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- ATAD3A | 1 (1.2%) | – | 1 (3.2%) | 0.2 |
- DARS2 | 1 (1.2%) | 1 (1.8%) | – | 0.4 |
- SLC19A3 | 1 (1.2%) | – | 1 (3.2%) | 0.2 |
Extra-cardiac manifestations (n°; %) | ||||
- Failure to thrive | 28 (32.5%) | 12 (21.8%) | 16 (51%) | 0.1 |
- Neurologic | 52 (60.4%) | 33 (60%) | 19 (52.7%) | 0.9 |
o neurodevelopmental delay | 36 (42%) | 21 (38%) | 15 (48%) | – |
o epilepsy | 28 (32.5%) | 14 (25.5%) | 4 (13%) | – |
o hypo- or hypertonia | 17 (19.7%) | 7 (12.7%) | 10 (32%) | – |
o recurrent headache/cerebral stroke | 6 (7%) | 3 (5.5%) | 3 (9.7%) | - - |
- Ocular | 16 (18.6%) | 6 (11%) | 10 (32%) | 0.1 |
- Hearing loss | 8 (9.3%) | 2 (3.6%) | 6 (19.3%) | 0.3 |
- Diabetes | 5 (5.8%) | 1 (1.8%) | 4 (13%) | 0.1 |
- Renal failure | 6 (7%) | 1 (1.8%) | −5 (16%) | 0.04 |
Cardiac involvement | 31 (36%) | – | 31 (100%) | n.a. |
Clinical presentation | ||||
- Asymptomatic | Â | Â | 18 (58%) | Â |
- Cardiac murmur | Â | Â | 5 (16%) | Â |
- Heart failure | Â | Â | 6 (19.3%) | Â |
- Prenatal suspicion | Â | Â | 2 (6.4%) | Â |
- Systemic hypertension | Â | Â | 3 (9.7%) | Â |
Baseline electrocardiographic anomalies (n°;%) |  |  | 23 (74.1%) | n.a. |
- Atrial enlargement | Â | Â | 3 (9.6%) | Â |
- LV hypertrophy/volume overload | Â | Â | 14 (45%) | Â |
- Right bundle branch block | Â | Â | 7 (22.5%) | Â |
- Ventricular pre-excitation | Â | Â | 2 (6.4%) | Â |
- Increased QTc interval | Â | Â | 1 (1.8%) | Â |
- Premature atrial complexes | Â | Â | 1 (1.8%) | Â |
Baseline echocardiographic findings (n°;%) | ||||
- HCM | Â | Â | 13 (42%) | Â |
- HCM/NC | Â | Â | 4 (13%) | Â |
- DCM | Â | Â | 8 (25.8%) | Â |
- PAH | Â | Â | 4 (13%) | Â |
Major cardiac events (n°; %) |  |  | 6 (19%) |  |
- Hospitalization due to HF | Â | Â | 2 (6.4%) | Â |
- Decease due to HF | Â | Â | 2 (6.4%) | Â |
- Resuscitated cardiac arrest | Â | Â | 1 (1.8%) | Â |
- PM implantation (high-grade AV block) | Â | Â | 1 (2.8%) | Â |
- Sudden cardiac death | Â | Â | 1 (1.8%) | n.a. |
Mortality | 26 (30.2%) | 12 (21.8%) | 14 (45.1%) | < 0.01 |
- Cardiac cause | Â | Â | 3 (9.6%) | Â |
- Respiratory infection | Â | Â | 2 (6.4%) | Â |
- Metabolic crisis | Â | Â | 2 (6.4%) | Â |
- Stroke | Â | Â | 1 (1.8%) | Â |
- Not assessed | Â | Â | 6 (19%) | Â |