Reversible Multiorgan System Involvement in a Neonate With Complex IV Deficiency Evonne Low, MB*, Ellen B. Crushell, MB*, Sinead B. Harty, MB*, Stephanie P. Ryan, MB † , and Eileen P. Treacy, MD* Mitochondrial respiratory chain deficiencies can pres- ent as fulminant liver failure or disease, and the prog- nosis when associated with severe neonatal lactic acidosis is frequently guarded. We report the case of a neonate who presented with acute liver failure and fulminant lactic acidosis with profound complex IV deficiency documented in muscle and liver biopsies. The neonate subsequently experienced clinical resolu- tion by 3 months of age, and was observed to have reversibility of the biochemical deficiency noted in muscle. This case illustrates that resolution of this severe neonatal phenotype does occur, of importance for accurate prognostic and genetic counseling for such affected neonates. Ó 2008 by Elsevier Inc. All rights reserved. Low E, Crushell EB, Harty SB, Ryan SP, Treacy EP. Re- versible multiorgan system involvement in a neonate with complex IV deficiency. Pediatr Neurol 2008;39:368-370. Introduction Mitochondrial respiratory chain deficiencies can present as fulminant liver failure or disease [1-5]. Hepatocerebral syndrome may be caused by isolated inherited complex IV (cytochrome oxidase [COX]) deficiency or disorders of mitochondrial depletion. The prognosis for these condi- tions when presenting with severe neonatal lactic acidosis is frequently guarded, in particular with associated liver dis- ease at presentation [6]. The phenomenon of reversibility past the neonatal period of neonatal lactic acidosis and of profound liver complex IV deficiency has been previously reported [7-9]. Here, we describe the case of a neonate who presented with acute liver failure and fulminant lactic acidosis and who was subsequently determined to have profound com- plex IV deficiency in both a liver and muscle sample. At 3 months after presentation, the infant experienced clinical resolution, which was subsequently confirmed by the find- ings of normal complex IV activity from a muscle biopsy sample taken from the infant. Case Report A female infant was born at term after a normal pregnancy and delivery to nonconsanguineous parents of Irish ancestry. There were three other healthy children born to the family, and there was no family history of note. The infant’s birth weight was 2.49 kg (2nd percentile), the length was 44 cm (2nd percentile), and the head circumference was 33 cm (9th percentile). The perinatal course was uneventful. She presented at day 6 of life with poor feeding, jaundice, and weight loss. On evaluation, she was noted to be acidotic, with elevation of liver transaminases enzymes (aspartate aminotransferase, 195 IU/L [normal reference range, 0-54 IU/ L]; alanine aminotransferase, 114 IU/L [normal reference range, 0-67 IU/L]) and had mixed conjugated hyperbilirubinemia (total bilirubin, 181 mmol/L [normal reference range, 0 to 17 mmol/L]; conjugated biliru- bin, 145 mmol/L [normal reference range, 0-5 mmol/L]). In addition, a coa- gulopathy was noted: the prothrombin time was greater than 180 seconds (normal reference range, 11.5-15.3 seconds), and the activated partial thromboplastin time (APTT) was greater than 120 seconds (normal refer- ence range, 35.1-46.3 seconds). Screening markers for sepsis were nega- tive. Other investigations yielded normal results, including cholesterol and triglyceride levels, a copper–ceruloplasmin level, a-1 antitrypsin, serum ferritin, and plasma total iron binding capacity levels. The trans- ferrin saturation was high at 100 mmol/L (normal reference range, 15-50 mmol/L); however, a salivary gland biopsy to rule out neonatal hemach- romatosis yielded negative results for iron storage. A liver ultrasound did not show any abnormality. At presentation, the plasma lactate ranged from 7 to 18 mmol/L (normal reference range, 0.6-2.4 mmol/L), a plasma ammonia level was slightly elevated at 137 mmol/L; this subsequently decreased to normal values. The cerebrospinal fluid (CSF) lactate was 2.4 mmol/L (normal reference range, 0.9-2.4 mmol/L); the CSF protein analysis was normal, as was the CSF amino acid analysis. Plasma amino acid analysis showed a general- ized aminoaciduria, but this normalized 1 week later. Analysis of urinary organic acids was consistent with liver dysfunction, with phenylalanine metabolites, phenyllactate and phenylpyruvate present and a mild eleva- tion of ethylmalonic acid. An acylcarnitine profile was within normal limits. On examination, her weight and length were on the 3rd percentile, From the *National Centre for Inherited Metabolic Disorders and †Department of Radiology, Children’s University Hospital, Temple Street. Dublin, Ireland. Communications should be addressed to: Dr. Treacy; National Centre for Inherited Metabolic Disorders; Children’s University Hospital; Temple Street; Dublin 1, Ireland. E-mail: eileen.treacy@cuh.ie Received April 17, 2008; accepted July 28, 2008. 368 PEDIATRIC NEUROLOGY Vol. 39 No. 5 Ó 2008 by Elsevier Inc. All rights reserved. doi:10.1016/j.pediatrneurol.2008.07.023  0887-8994/08/$—see front matter