Thématique :
- Foie
Originalité :
Très original
Solidité :
A confirmer
Doit faire évoluer notre pratique :
Dans certains cas
Nom du veilleur :
Docteur Jean-Louis PAYEN
Coup de coeur :
Journal of Hepatology
  2016 Aug;65(2):377-85  
  doi: 10.1016/j.jhep.2016.04.017  
  Severe respiratory complex III defect prevents liver adaptation to prolonged fasting  
  Kremer LS, L'hermitte-Stead C, Lesimple P, Gilleron M, Filaut S, Jardel C, Haack TB, Strom TM, Meitinger T, Azzouz H, Tebib N, Ogier de Baulny H, Touati G, Prokisch H, Lombès A  

Background & Aims

Next generation sequencing approaches have tremendously improved the diagnosis of rare genetic diseases. It may however be faced with difficult clinical interpretation of variants. Inherited enzymatic diseases provide an invaluable possibility to evaluate the function of the defective enzyme in human cell biology. This is the case for respiratory complex III, which has 11 structural subunits and requires several assembly factors. An important role of complex III in liver function is suggested by its frequent impairment in human cases of genetic complex III defects.


We report the case of a child with complex III defect and acute liver dysfunction with lactic acidosis, hypoglycemia, and hyperammonemia. Mitochondrial activities were assessed in liver and fibroblasts using spectrophotometric assays. Genetic analysis was done by exome followed by Sanger sequencing. Functional complementation of defective fibroblasts was performed using lentiviral transduction followed by enzymatic analyses and expression assays.


Homozygous, truncating, mutations in LYRM7 and MTO1, two genes encoding essential mitochondrial proteins were found. Functional complementation of the complex III defect in fibroblasts demonstrated the causal role of LYRM7 mutations. Comparison of the patient’s clinical history to previously reported patients with complex III defect due to nuclear DNA mutations, some actually followed by us, showed striking similarities allowing us to propose common pathophysiology.


Profound complex III defect in liver does not induce actual liver failure but impedes liver adaptation to prolonged fasting leading to severe lactic acidosis, hypoglycemia, and hyperammonemia, potentially leading to irreversible brain damage.

Lay summary

The diagnosis of rare genetic disease has been tremendously accelerated by the development of high throughput sequencing technology. In this paper we report the investigations that have led to identify LYRM7 mutations causing severe hepatic defect of respiratory complex III. Based on the comparison of the patient’s phenotype with other cases of complex III defect, we propose that profound complex III defect in liver does not induce actual liver failure but impedes liver adaptation to prolonged fasting.

Question posée
Le défécit en « Severe respiratoire complexe III » empêcherait l'adaptation du foie à un jeûne prolongé.
Question posée
Le déficit en « Severe respiratoire complexe III » dans le foie ne provoque pas une insuffisance hépatique. Toutefois, elle empêche l'adaptation du foie à un jeûne prolongé conduisant à une acidose lactique sévère, une hypoglycémie et une hyperammoniémie, pouvant conduire à des lésions cérébrales irréversibles .

A propos d’un cas.