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.