TABLE 3

Characteristics of patients harbouring MARS mutations

Van Meel [30]Hadchouel [31, 32]Sun [33]Rips [34]Abuduxikuer [35]Alzaid [36]
Mutations# and location on the protein structureF370L/I523T
CAT
Y344C/A393T/
S567L/D605V
CAT
D145N/F802S
ABD/PBD
Y307C/R618C
CAT
R299_S300insR/Q720#
CAT/ABD
I285Y
CAT
Subjects1 male, age 1 month15 males and 7 female, age 2.8 (0.5–72) months
3 males and 1 female, ages 2 (1–2.5) months
1 male, age 10 months
1 male and 1 female, age 3.6 years and 3.9 years
2 males, age 1 month1 male, neonatal period1 female, age 5 months1 male, neonatal period
CountryUSARéunion, n=22
Comoros n=4
Caucasian/Réunion n=1
Tunisia n=2
ChinaIsrael from Jewish Moroccan/Tunisian/Persian descentChinaSaudi Arabia
Lung involvementILDPAPILD, fibrosisILD with foamy macrophagesILD, compatible with PAP on chest CT scan, no BALPAP
Other featuresFTT, HMG, cholestasis, liver failure, hypothyroidism, anaemia, hypotonia, developmental delay, acidosis, aminoaciduriaFTT, HMG, cholestasis, anaemia, inflammation with hyperleukocytosis, thrombocytosis, and high IgG level, hypoalbuminaemiaFTT, anaemia HMG, liver failure, acidosis, hypotonia, developmental delayAnaemia, hypothyroidism, HMG, cholestasis, liver failure, developmental delay, aminoaciduriaFTT, cholestasis, liver failure, HMG, inflammation, anaemia, thrombocytosis, hyperleukocytosis, prolonged fever, kidney stones, developmental delay, acetabular dysplasiaFTT, intermittent fever, hypotonia, HMG, hypoglycaemia, hypothyroidism, anaemia, thrombopenia
Last follow-upAge 3.5 years, stable on TPN and nasal oxygenDeath: n=13, 1.5 (0.4–25.2) years
Asymptomatic: n=6, 6.3 (4.2–18.1) years
Symptomatic no oxygen: n=2, 5.2 and 22.3 years
CRF+: n=8, 10.6 (1.1–24.9) years
Death: n=1 at 9 months
Stable: n=1 at 4.2 years
Age 1 year, improvement under methionine supplementationDeath at 11 monthsDeath at 6 months
Functional studiesReduced aminoacylation activity, normal association with MSCReduced aminoacylation activity, normal association with MSCNoneGrowth arrest in mutated yeastNoneNone

Data are presented as median (min–max), unless otherwise stated. CAT: catalytic domain; ABD: anticodon-binding domain; PBD: protein-binding domain; ILD: interstitial lung disease; CT: computed tomography; PAP: pulmonary alveolar proteinosis; BAL: bronchoalveolar lavage; FTT: failure to thrive; HMG: hepatomegaly; Ig immunoglobulin; MSC: multiaminoacyl-tRNA synthetase complex; TPN: total parenteral nutrition; CRF: chronic respiratory failure. #: protein nomenclature is given; : no imaging or pathological data given; +: chronic respiratory failure with oxygen therapy either continuous, nocturnal or on exertion.