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Umetsu et al. Hepatoma Res 2020;6:1 I http://dx.doi.org/10.20517/2394-5079.2019.030 Page 7 of 10

Table 2. Clinical phenotype of patients with MPV-17-related mitochondria hepatopathy with p.R50Q, or p.R50W mutations
p.R50Q/p.R50W n = 3 p.R50W reported n = 5 p.R50Q reported n = 11
Sex Female 2 (67) 4 (80) 4 (36)
Outcome Alive 3 (100) 0 (0) 5 (46)
Liver transplantation 2 (66) 1 (20) 5 (46)
Hepatic symptoms 3 (100) 5 (100) 11 (100)
HCC 1 (33) 1 (20) 1 (9)
Hepatomegaly 3 (100) 3 (60) 3 (27)
Cirrhosis 2 (67) 1 (20) 6 (55)
Liver dysfunction 3 (100) 5 (100) 11 (100)
Liver failure 2 (67) 5 (100) 9 (82)
Cholestasis 0 (0) 3 (60) 8 (73)
Steatosis 0 (0) 4 (80) 7 (64)
Neurological symptoms 1 (33) 4 (80) 10 (91)
Ataxia 0 (0) 0 (0) 2 (18)
Corneal ulcers 0 (0) 0 (0) 3 (27)
Developmental delay 1 (33) 2 (40) 9 (82)
Dystonia 0 (0) 2 (40) 0 (0)
Hypotonia 0 (0) 2 (40) 3 (27)
Peripheral neuropathy 0 (0) 0 (0) 8 (73)
Seizures 0 (0) 1 (20) 1 (9)
MRI abnormality
Basal ganglia 0 (0) 1 (20) 0 (0)
White matter 0 (0) 2 (40) 5 (46)
Metabolic symptoms 3 (100) 3 (60) 10 (91)
Lactic acidemia 0 (0) 3 (60) 8 (73)
Hypoglycemia 3 (100) 2 (40) 7 (64)
GI symptoms 3 (100) 4 (80) 8 (73)
Feeding difficulties 0 (0) 2 (40) 0 (0)
Failure to thrive 3 (100) 4 (80) 8 (73)

The data are numbers (percentages). HCC: hepatocellular carcinoma; GI: gastrointestinal; MRI: magnetic resonance imaging

Table 3. Clinical manifestations of patients with MPV17-related hepatocerebral mitochondrial DNA depletion syndrome who
developed hepatocellular carcinoma
Case 2 Patient 1 Patient 2 Patient 3
Sex Female Male Male Female
Ethnicity Japan Navajo Caucasian India
MPV17
Allele 1 p.R50Q p.R50Q c.22insC p.R50W
Allele 2 p.R50W p.R50Q NA p.R50W
Onset age 4 years Infancy Infancy 5 years
LT (age) Done (7 years) Done (11 years) Done (NA) Done (9 years)
Outcome (age) Alive (8 years) Alive (21 years) Alive (9 years) Died (10 years)
Hepatic manifestation Cirrhosis, HCC LF, Cirrhosis, Steatosis, HCC LF, Cirrhosis, HCC LF, Cirrhosis, Steatosis, HCC
Other manifestation Hypoglycemia, FTT DD, Peripheral neuropathy, MRI DD, Hypotonia, Seizures, Dystonia, MRI
abnormalities, Hypoglycemia, FTT Seizures, FTT abnormalities, FTT
Ref. This report [10] [15] [25]
HCC: hepatocellular carcinoma; DD: developmental delay; FTT: failure to thrive; GI: gastrointestinal; LF: liver failure; LT: liver
transplantation; NA: not accessed; MRI: magnetic resonance imaging

Liver transplantation is one of the best treatments for HCC-induced cirrhotic liver. Although a recent
study showed that liver transplantation for pediatric HCC patients with inherited metabolic disease has
[33]
better chances of survival compared with pediatric HCC patients with non-inherited metabolic disease ,
its efficacy in MPV17-MTDPS remains controversial. The reason behind this is that the organ’s systemic
complexity results in high morbidity during post-transplantation. Of the 17 known MPV17-related MTDPS
[30]
patients who received liver transplantation, seven (41%) died during the post-transplantation period . Of