OUTCOME OF MITOCHONDRIAL CYTOPATHIES PRESENTING WITH LIVER INVOLVEMENT

Abstract

Aim: In the absence of a readily available diagnostic test for mitochondrial cytopathies (MC) we investigated clinical features of children with liver dysfunction eventually diagnosed with MC. Methods: A retrospective review of cases referred to a tertiary centre between 1991 and 2004 was made. Diagnostic criteria included: a) reduced muscle respiratory enzyme complex I-V activity (<20% of age adjusted mean value), b) presence of mt DNA mutations, c) clinical evidence of a recognised mitochondrial syndrome, or d) combination of suggestive biochemical and radiological features (elevated serum and/or CSF lactate, abnormal brain MRI), family history and reduced enzyme activity (20-40%). Results: 24 children (17 male, 71%) were identified. Median age at presentation was 0.33y (range,0-5).12 (50%) children were from consanguineous families. Presenting features were acute liver failure (ALF)(10), biochemical liver dysfunction (12), and hepatosplenomegaly (2). Extrahepatic involvement included neurological (18), haematological (3), renal (5), pancreatic (2) and failure to thrive (8). Median serum lactate was 3.45 mmol/L (range,0.9-17.0) and CSF lactate 1.5 mmol/L (range,1-6.45). Brain MRI was abnormal in 11/15 children with either atrophy or changes in the brain stem or basal ganglia. Diagnosis was confirmed on muscle or liver enzymology in 20 [deficiency of complexes IV (9), I (5), I & IV (2) and II & III (4)] and mt DNA analysis in 1. Alpers (2), Leigh (1) and Pearson sy. (1) were diagnosed in 4 patients. 14 children died at a median age of 1.8y (range, 0-5.4). 2 boys underwent transplantation due to deepening liver failure. One of them died from progressive respiratory failure 10 months later. The other is well with normal neurodevelopment and graft function 3y post-transplant. Of the 10 survivors, 2 have cirrhosis, while in 8 the liver function stabilised after a median follow up of 3.9y (range, 0.5-13.8). Conclusions: MC should be sought in all children with cryptogenic liver disease, including ALF. Of the non-invasive clinical tests only brain MRI appears to be helpful Overall prognosis is poor and consideration of liver transplantation should be confined to those without neurological involvement.