Table 1.
Abbreviated clinical summary of patients with pathogenic variants in IARS2
| Patient 1 (Present study) | Patient 2 (Present study) | Patient 3 (Present study) | Patient 4 Takezawa et al., 2018 [9] | Patient 5 Takezawa et al., 2018 [9] | Patient 6 Moosa et al., 2017 [7] | Patient 7 (Case 1 in Schwartzentruber et al., 2014 [5]; Jabbour and Harissi-Dagher, 2016 [29] | Patient 8 Case 2 in Schwartzentruber et al., 2014 [5] Patient 1 Liberfarb et al., 1993 [6] | Patient 9 Case 3 in Schwartzentruber et al., 2014 [5] Patient 2 Liberfarb et al., 1993 [6] | Patient 10 Case 4 in Schwartzentruber et al., 2014 [5] | |
|---|---|---|---|---|---|---|---|---|---|---|
| Ethnic descent | Iranian | Iranian | Iranian | Japanese | Japanese | Danish | French-Canadian | French-Canadian | French-Canadian | Scandinavian-Caucasian |
| Sex | Male | Female | Female | Female | Female | Female | Female | Male | Female | Male |
| Age at publication | 20.6 years | 35 years | 27 years | 8 years | 5 years | 8 years | 33 years | 6 years | 16.5 years | 18 months |
| Genotype | c.2725C > T p.Pro909Ser | c.2282A > G p.His761Arg | c.2282A > G p.His761Arg | c.680 T > C, p.Phe227Ser; c.2450G > A, p.Arg817His | c.680 T > C, p.Phe227Ser; c.2450G > A, p.Arg817His | c.2620G > A p.Gly874Arg | c.2726C > T p.Pro909Leu | c.2726C > T p.Pro909Leu | c.2726C > T, p.Pro909Leu | c.1821G > A p.Trp607*; c.2122G > A p.Glu708Lys |
| Ocular evaluation | ||||||||||
| Bilateral nystagmus | Yes | Yes | Yes | – | – | Yes | Yes, at 1 month | Yes, at 5 months | Yes, 3 months | – |
| Cataract | Yes, at birth | Yes, at birth | Yes, at birth | Yes, at birth | – | Yes, at 3 years | Yes, at 17 months; cataract extraction at 22 months | Yes, at 5 months; cataract extraction at 7 months | Yes, 3 months; cataract extracted at 13 months | – |
| Corneal opacification | Yes | Yes | Yes | – | – | – | Yes, at 5 years, progressive | Yes, at 5 years | Yes, at 16 years 5 months | – |
| Endocrinology | ||||||||||
| Endocrine disturbances | Central adrenal insufficiency, growth hormone deficiency | – | – | – | – | – | Adrenal insufficiency, growth hormone deficiency | – | – | – |
| Growth hormone replacement therapy | – | – | – | – | – | – | Yes, positive outcome | Yes, positive outcome (cortisol deficiency) | – | – |
| Hypoglycemic Episodes | – | – | – | – | – | – | Yes | – | Yes | Yes |
| Auditory evaluation | ||||||||||
| Hearing loss | Moderate bilateral sensorineural hearing loss at 13 years of age | – | – | – | – | Bilateral sensorineural hearing loss at 8 years old | Bilateral sensorineural stable hearing loss at 2 years old | Moderate bilateral sensorineural hearing loss at 21 months | – | – |
| Gastroenterology | ||||||||||
| Type II esophageal Achalasia | Yes, from birth | – | – | – | – | – | Yes, 32 years | – | – | – |
| Musculoskeletal | ||||||||||
| Short stature | Yes, proportionate (−3.4 SD) | Yes | Yes | Yes | Yes | Yes, disproportionate (−6 SD), | Yes, disproportionate | Yes | Yes | – |
| Hip dislocation | – | – | – | – | – | Yes, at birth | Yes, at 2 years | Yes, at birth | Yes, at 18 months | – |
| Spine abnormalities | Yes, mild scoliosis | – | – | Yes | Yes | Yes, abnormal vertebral bodies | Yes, mild scoliosis | Yes, scoliosis | Yes, scoliosis | |
| Spondylo-epi-meta- physeal dysplasia | Yes | Yes, disproportional shortening of the first metacarpal reduced bone density | Yes, disproportional shortening of the first metacarpal | – | – | Yes | Yes | Yes | Yes | – |
| Neurological and Developmental Assessment | ||||||||||
| Leigh syndrome features | – | – | – | Yes | Yes | – | – | – | – | Yes |
| West syndrome | – | – | – | Yes | Yes | – | – | – | – | – |
| Neurodevelopmental Delay | Yes | – | – | Yes | Yes | Yes | Yes, mild | Yes | Yes | Yes |
| Current normal Intelligence | Yes | Yes | Yes | – | – | Yes | Yes | – | Yes | ? |
| Peripheral neuropathy | Chronic sensorimotor distal axonal polyneuropathy | – | – | – | – | Yes, pain insensitivity in early childhood | Yes, at 9.5 years | Yes, in early childhood | Yes, at 8 months | – |