Table 1 Genotype and clinical phenotype of novel ILFS1 patients.

From: Genotypic diversity and phenotypic spectrum of infantile liver failure syndrome type 1 due to variants in LARS1

Patient ID

Family

Sex

Descent

Alive (Y/N)

Age at diagnosis (years)

Age at last visit (years)

Allele 1 NM_020117.11 NP_064502.9

Allele 2 NM_020117.11 NP_064502.9

Aminoacylation activity of LARS1 at 37 °C (% control)

Aminoacylation activity of LARS1 at 40 °C (% control)

Gestational age (weeks)

Growth

Nervous system

Blood

Liver

Musculature

Hypoalbuminemia

LARS1-01

I

F

DE

Y

11

12

c.(1292T>A);

p.(Val431Asp)

c.(641A>G);

p.(Tyr214Cys)

60

44

34

IUGR, SGA

Neurodevelopmental delay, infection-associated seizures, encephalopathic crises with seizures

Microcytic hypochromic anemia

Recurrent ELT, RALF; biopsy (4 years): steatosis

Hypotonia

Y

LARS1-02

II

M

DE

Y

3

6

c.(1292T>A);

p.(Val431Asp)

c.(2445G>T);

p.(Met815Ile)

43

11

37

IUGR, SGA, short stature

Neurodevelopmental delay

Microcytic anemia

Recurrent ELT, ALF; biopsy (1 year): cirrhosis

Hypotonia

Y

LARS1-03

III

M

DE

Y

6

8

c.(1292T>A);

p.(Val431Asp)

c.(1284+1delG);

p.(?)

70

31

35

IUGR, SGA, short stature, failure to thrive

Neurodevelopmental delay, infection-associated seizures, encephalopathic crisis with seizures

Microcytic hypochromic anemia

Recurrent ELT, ALF; biopsy (1 year): cirrhosis

Hypotonia

Y

LARS1-04

IV

M

NL

Na

Post mortem

1.8

c.(3420del);

p.(Ile1141Phefs*12)

c.(587G>C);

p.(Gly196Ala)

80

27

38

SGA, failure to thrive, decreased body weight, short stature, antenatal growth ND

Neurodevelopmental delay, encephalopathic crises with seizures, spastic diplegia, flexion spasms of left arm and legs following first encephalopathic episode

Microcytic hypochromic anemia

Recurrent ELT, ALF; biopsy (0.3 years): normal

Hypertonia following first encephalopathic crisis

Y

LARS1-05

IV

F

NL

Y

23

23

c.(3420del);

p.(Ile1141Phefs*12)

c.(587G>C);

p.(Gly196Ala)

85

49

34

IUGR, SGA, failure to thrive

Neurodevelopmental delay, encephalopathic crises with seizures

Microcytic hypochromic anemia

Recurrent ELT; no biopsy done

Hypotonia

Y

LARS1-06

V

F

SY

Y

3

6

c.(3313C>T);

p. (Arg1105*)

c.(3313C>T);

p.(Arg1105*)

70

45

Term

Decreased body weight, short stature, failure to thrive, birth weight and antenatal growth ND

Neurodevelopmental delay

No abnormality

Ultrasound with hints of steatosis; no biopsy done

Hypotonia

N

LARS1-07

V

M

SY

Y

5

8

c.(3313C>T);

p.(Arg1105*)

c.(3313C>T);

p.(Arg1105*)

NA

NA

Term

Decreased body weight, short stature, failure to thrive, birth weight and antenatal growth ND

Neurodevelopmental delay, seizures

Microcytic hypochromic anemia

N; no biopsy done

Hypotonia

Y

LARS1-08

VI

M

FR

Y

12

12

c.(1292T>A);

p.(Val431Asp)

c.(644A>C);

p.(Asp215Ala)

NA

NA

35

IUGR, SGA, failure to thrive

Neurodevelopmental delay, infection-associated seizures

Microcytic anemia

Recurrent ELT, RALF; biopsy (0.9 years): fibrosis

Hypotonia

Y

LARS1-09

VII

M

US

Y

3

3

c.(2003T>A);

p.(Val668Asp)

c.(2445G>T);

p.(Met815Ile)

NA

NA

32

IUGR, SGA, failure to thrive

Neurodevelopmental delay, infection-associated seizures, encephalopathic crises with seizures

Microcytic anemia

ALF, transplanted after first ALF aged 4 months; biopsy (0.1 years): fibrosis

No abnormality

Y

LARS1-10

VIII

F

DE

Y

1

3

c.(1292T>A);

p.(Val431Asp)

c.(1838_1843del);

p.(Gly613_Leu615delinsVal)

35

22

32

IUGR, SGA, failure to thrive

Neurodevelopmental delay, encephalopathic crisis with seizures

Microcytic anemia

Recurrent ELT, ALF; steatosis; no biopsy done

Hypotonia

Y

LARS1-11

VIII

F

DE

Y

0.1b

1

c.(1292T>A);

p.(Val431Asp)

c.(1838_1843del);

p.(Gly613_Leu615delinsVal)

NA

NA

34

IUGR, SGA, failure to thrive

Neurodevelopmental delay

Microcytic anemia

Hepatomegaly, ELT

Hypotonia

Y

LARS1-12

IX

M

IE

Y

0.4

1

c.(1118A>G);

p.(Tyr373Cys)

c.(1118A>G);

p.(Tyr373Cys)

NA

NA

36

IUGR, SGA, failure to thrive

Neurodevelopmental delay

Microcytic hypochromic anemia

Recurrent ELT, ALF

Mild hypotonia

Y

Previously published cases (n = 13)

 

M (8) F (5)

 

Y (9/13)

      

Premature birth (7/13)

SGA (13/13),

IUGR (2/2),

failure to thrive (12/13),

short stature (6/13)

Encephalopathic crises (7/12),

seizures (infection-associated) (11/12),

neurodevelopmental delay (10/12),

motor delay (8/12)

Microcytic anemia (13/13)

Recurrent ELT (13/13),

ALF (8/13),

RALF (4/13)

Muscular hypotonia (7/9)

Hypoalbuminemia (13/13)

All cases (n = 25)

 

15 M 10 F

 

20/25 Alive

      

15/25 Premature birth

25/25 Abnormality of growth

24/24 Abnormality of the nervous system

24/25 Abnormality of the blood

24/25 Abnormality of the liver

18/21 Abnormality of the musculature

24/25 Hypoalbuminemia

  1. Numbers in parentheses indicate affected individuals per total number of patients with available data, e.g., ALF (8/13): 8 individuals experienced ALF, data available for 13 patients. Descent is displayed in international two letter country code (DE Germany, NL Netherlands, SY Syrian Arab Republic, FR France, US United States of America, IE Ireland). For definitions of ALF and RALF see Supplementary Data. NA indicates “not applicable” (aminoacylation activity not measured as fibroblasts were not available).
  2. ALF acute liver failure, ELT elevated liver transaminases, ILFS1 infantile liver failure syndrome 1, IUGR intrauterine growth retardation, RALF recurrent acute liver failure, SGA small for gestational age.
  3. aLARS1-04 deceased aged 1.8 years during an encephalopathic episode.
  4. bPre-emptive family history triggered diagnosis.
Back to article page