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Table 2 Clinical features, muscular biopsy, molecular diagnosis and outcome in enrolled patients

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%)  
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%)  
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    18 (58%)  
- Cardiac murmur    5 (16%)  
- Heart failure    6 (19.3%)  
- Prenatal suspicion    2 (6.4%)  
- Systemic hypertension    3 (9.7%)  
Baseline electrocardiographic anomalies (n°;%)    23 (74.1%) n.a.
- Atrial enlargement    3 (9.6%)  
- LV hypertrophy/volume overload    14 (45%)  
- Right bundle branch block    7 (22.5%)  
- Ventricular pre-excitation    2 (6.4%)  
- Increased QTc interval    1 (1.8%)  
- Premature atrial complexes    1 (1.8%)  
Baseline echocardiographic findings (n°;%)
- HCM    13 (42%)  
- HCM/NC    4 (13%)  
- DCM    8 (25.8%)  
- PAH    4 (13%)  
Major cardiac events (n°; %)    6 (19%)  
- Hospitalization due to HF    2 (6.4%)  
- Decease due to HF    2 (6.4%)  
- Resuscitated cardiac arrest    1 (1.8%)  
- PM implantation (high-grade AV block)    1 (2.8%)  
- Sudden cardiac death    1 (1.8%) n.a.
Mortality 26 (30.2%) 12 (21.8%) 14 (45.1%) < 0.01
- Cardiac cause    3 (9.6%)  
- Respiratory infection    2 (6.4%)  
- Metabolic crisis    2 (6.4%)  
- Stroke    1 (1.8%)  
- Not assessed    6 (19%)  
  1. Abbreviations: CVI cardiovascular involvement; LFUP last follow-up; LV left ventricle; HCM hypertrophic cardiomyopathy; NC non-compaction; DCM dilative cardiomyopathy; PAH pulmonary hypertension; HF heart failure; PM pace-maker; AV atrioventricular