Mevalonate kinase deficiency masked by cytomegalovirus infection and obscure liver disease.

BACKGROUND: Chronic liver disease with conjugated hyperbilirubinaemia and failure to thrive can have multifactorial aetiologies. Investigations can be complex and difficult especially when obscured by a viral infection affecting liver function. METHODS: A 5 month old male infant was referred for investigation of chronic liver disease and a history of jaundice with multiple febrile episodes. Liver function tests were performed followed by a liver biopsy and microbiological workup for infectious disease. In addition, urine analysis of organic acids was also performed. RESULTS: There was marked conjugated hyperbilirubinaemia with markedly elevated hepatocellular enzymes and normal ductal enzymes. Proteinuria and near normal renal function suggested early renal impairment. There was also leukocytosis and bicytopenia. An extensive bacteriological investigation including TB workup was negative. CMV infection was confirmed by viral load and antibody reactivity. There was prolonged PT and PTT and high INR. The liver biopsy showed giant cell transformation of hepatocytes with mild cholestasis, portal and peri-cellular fibrosis with alpha-1-antitrypsin positive granules in the hepatocyte cytoplasm suggesting alpha-1-antitrypsin deficiency. Urine organic acids revealed significantly elevated mevalonolactone. CONCLUSIONS: We confirmed the genetic diagnosis of mevalonic aciduria caused by MVK deficiency which had been masked by liver disease and the possible misdiagnosis of alpha-1-antitrypsin deficiency.

Adjunctive corticosteroid treatment of clinical Pneumocystis jiroveci pneumonia in infants less than 18 months of age--a randomised controlled trial.

OBJECTIVES: To determine the efficacy and safety of adjunctive corticosteroid therapy in clinical Pneumocystis jiroveci pneumonia (PCP) in infants exposed to HIV infection. DESIGN: Double-blind randomised placebo-controlled trial. METHODS: Infants with a clinical diagnosis of PCP, based on an 'atypical' pneumonia with: (i) hypoxia out of proportion to the clinical findings on auscultation; (ii) C-reactive protein count less than 10 mg/1; (iii) lactate dehydrogenase level above 500 IU/1; (iv) compatible chest radiograph findings; and (v) positive HIV enzyme-linked immunosorbert assay (ELISA) were included in the study. Patients were randomised to receive either prednisone or placebo. The protocol provided for the addition of prednisone to the treatment at 48 hours if there was clinical deterioration or an independent indication for steroid therapy. Other treatment was carried out in accordance with established guidelines. The primary study endpoint was in-hospital survival. Secondary outcome was time from admission to the first day of mean oxygen saturation above 90% in room air. RESULTS: One hundred patients were included, 47 in the prednisone and 53 in the placebo group. Patients in the prednisone group had a 43% better chance of survival than the placebo group (hazard ratio (HR) 0.57, 95% confidence interval (CI) 0.30 - 1.07, p=0.08). No significant differences could be demonstrated between groups with regard to other parameters of recovery. CONCLUSIONS: In HIV-exposed infants with clinical PCP, adjunctive corticosteroid treatment does not appear to add benefit regarding time to recovery or oxygen independency, but early administration may improve survival. A large multicentred trial is needed to confirm these findings.