Fatal neonatal hepatocellular deficiency with lactic acidosis: a defect of the respiratory chain

Abstract

Inborn errors of one or more of the complexes of the respiratory chain are increasingly being recognized as important causes of disease. Patients with these defects present in a variety of ways, including cases of fatal lactic acidosis in infancy. We describe here three cases of neonatal lactic acidosis in which the prominent features were hypertyrosinaemia and severe hepatic failure. They were shown to be the result of a defect in one or several complexes of the respiratory chain. Table 1. Mitochondria were isolated, when possible, from a muscle biopsy using the procedure of Morgan-Hughes and colleagues (1982). The respiratory activities are expressed in natom O rain-1 (rag protein)-1. The enzymatic assays were performed as described by Birch-Machin and colleagues (t989). The enzyme assays of fumaryl acetoacetase (FAA) were performed by Dr Berger (Groningen). PATIENTS AND METHODS AllA small part of the biopsy was also permeabilized in order to study respiratory parameters according to the methods of Veksler and colleagues (1987)

Clinical aspects of mitochondrial disorders

“…Permanent hyperlactataemia (10 mmol/L; normal < 2.,1. mmol/L) and markedly altered oxidoreduction status in plasma (lactate/pyruvate 30) prompted us to carry out a muscle biopsy and a needle biopsy of the liver. Panlobular fatty infiltration was found in the liver and cytochrome oxidase deficiency was present in both liver and skeletal muscle (Cormier et al 1991a;Parrot-Roulaud et al 1991).…”

Generalised Mitochondrial Cytopathy Is an Absolute Contraindication to Orthotopic Liver Transplant in Childhood

“…2). However, recently, a number of infants have been described with FHF as a manifestation of MC, but all have had concomitant neuromuscular involvement of neonatal onset, hyperlactataemia, or Fanconi syndrome(1‐4,15). Mitochondrial DNA depletion has been documented in two patients with infant‐onset liver failure as part of a multisystem disease (1,17).…”

“…Acute liver failure in infancy may related to sepsis, viral infections, adverse drug events, or many varied metabolic aetiologies. Recently a number of infants have been described with fulminant hepatic failure (FHF) as a manifestation of mitochondrial cytopathy (MC), but all have had concomitant neuromuscular involvement of neonatal onset(1‐4). Mitochondrial cytopathies are increasingly recognised in childhood.…”

Developmental and Inherited Liver Disease

“…The usual clinical features are either neonatal liver failure or else severe neonatal hepatitis syndrome. 1803,[1816][1817][1818][1819][1820][1821][1822] Children with mitochondrial respiratory chain defects may be at increased risk of developing hepatocellular carcinoma. 1823 A cytochrome-c oxidase deficiency found in Quebec kindreds may be associated with fatty liver.…”