Imaging spectrum of tyrosenimia: A rare metabolic disease entity. Poster No.: C-0028 Congress: ECR 2015 Type: Authors: Keywords: DOI: Educational Exhibit S. Solanki, K. Dave; Ahmedabad/IN Liver, Neuroradiology brain, CT, Ultrasound-Colour Doppler, Contrast agent-intravenous, Endoscopy, Acute, Cirrhosis, Infection 10.1594/ecr2015/C-0028 Any information contained in this pdf file is automatically generated from digital material submitted to EPOS by third parties in the form of scientific presentations. References to any names, marks, products, or services of third parties or hypertext links to thirdparty sites or information are provided solely as a convenience to you and do not in any way constitute or imply ECR's endorsement, sponsorship or recommendation of the third party, information, product or service. ECR is not responsible for the content of these pages and does not make any representations regarding the content or accuracy of material in this file. As per copyright regulations, any unauthorised use of the material or parts thereof as well as commercial reproduction or multiple distribution by any traditional or electronically based reproduction/publication method ist strictly prohibited. You agree to defend, indemnify, and hold ECR harmless from and against any and all claims, damages, costs, and expenses, including attorneys' fees, arising from or related to your use of these pages. Please note: Links to movies, ppt slideshows and any other multimedia files are not available in the pdf version of presentations. www.myesr.org Page 1 of 9
Learning objectives - To discuss the role of imaging in the evaluation of Tyrosinemia, which is a rare metabolic disease. - To review the Ultrasound (US) and Computed Tomography (CT) imaging findings of 3 cases of Tyrosinemia. Background Case History We present 3 cases of tyrosinemia type-i, which is a rare entity. First patient was 2 years old male child, who presented with history of diarrhea and vomiting since 5 months. His laboratory investigations showed increased amount of tyrosine, leucocytosis, increased alpha-fetoprotein level, increased Serum bilirubin and transaminase. Ultrasonography of the child showed presence of lobular regenerative nodules with cirrhotic changes in liver (Figure-1). Subsequent computed tomography (CT) confirmed cirrhotic nodules in the liver. Second patient was 1 year old child with complaints of extereme sleepiness, irritability and bloody diarrhoea. Investigations showed increased amount of tyrosine, serum bilirubin and transaminase. Ultrasound of the same patient showed hepatomegaly with fatty infiltration in the liver (Figure-2). CT scan of brain was also obtained which showed bilateral frontal sudural collections (Figure-3). Third child was 4 months old who had difficulty in swallowing, impaired motor activity and prolonged jaundice. Laboratory investigations showed increased amount of tyrosine, normocytic anemia, increased alpha-fetoprotein level, increased bilirubin and transaminase. CT scan of the abdomen showed large ill-defined heterogeneously enhancing lesion in right lobe of liver (Figure-4), which was confirmed to be hepatocellular carcinoma on biopsy. Findings and procedure details Page 2 of 9
Discussion Tyrosinemia is an autosomal recessive amino acid disorder. It was observed in one of the study in United States, that it occurs in 1 per 100,000 babies. It occurs due to deficiency of fumarylacetoacetate hydrolase (FAH), which is a terminal enzyme in the metabolism of tyrosine. This FAH enzyme is primarily synthesized in the liver, however it is also synthesized in adrenals, kidneys, heart, lungs, intestines, stomach, pancreas, lymphocytes and skeletal muscles. The accumulation of succinyiacetone leads to neurologic crises, acute and chronic liver failure, complex renal tubulopathy, rickets and a hemorrhagic syndrome. It affects liver and kidney in varying degree. Severe cases may lead to Hepatocellular carcinoma [1,2,3,6]. Infected patients present with abnormal liver function, hepatosplenomegaly, anemia, increased alpha-feto protein level and increased tyrosine levels. Acute form associated with liver failure and death. Chronic form is associated with cirrhosis, rickets and impaired renal function, tubulopathy and glomerular abnormalities [3,4]. Liver changes are most common in Tyrosinemia which includes chnages of cirrhosis with regenerative nodules or faaty infiltration or even space occupying lesion like hepatocellular carcinoma. Liver scintigraphy and angiography are useful in diagnosing hepatocellular carcinoma [4,5,7]. It has been noted that 2-(2-nitro-4 trifluoromethylbenzoyl)-1,3-cyclohexadione (NTBC) is a potent inhibitor of 4-hydroxyphenylpyruvate dioxygenase, the enzyme proximal to FAH in the tyrosine catabolic pathway. This drug can cause reversal of severe neurological crises in hours and also can reduce liver failure in 1 or 2 days. The renal tubulopathy and glomerular abnormalities can also get reversed in few days or even weeks. However, it remains unlikely that NTBC will prevent hepatocarcinoma in affected children. Liver transplantation remains the only definitive therapy for tyrosinemia [8,9]. Images for this section: Page 3 of 9
Fig. 1: Ultrasonography section of liver shows multiple echogenic cirrhotic nodules of varying sizes. Page 4 of 9
Fig. 2: Ultrasonography of liver showed mild enlargement of liver with fatty infiltration. Page 5 of 9
Fig. 3: Axial CT scan of brain showed symmetrical bilateral frontal subdural collections. Page 6 of 9
Fig. 4: Axial Contrast enhanced CT scan image of liver showed nodular heterogeneously enhancing space occupying lesion in right lobe of liver, which was confirmed to be hepatocellular carcinoma. Page 7 of 9
Conclusion Tyrosinemia is a very rare metabolic disease entity which should not be ignored as it can result into hepatic and renal failure. Radiologic imaging findings are very useful as ultrasound and CT can diagnose liver or kidney disease. Transplantation is the best available treament for tyrosinemia in cases of cirrhotic nodules or hepatocellualr carcinoma. Personal information References 1. Goldsmith LA. Tyrosinemia and related disorders. In: Stanbury JB. Wyngander JB, Fredrickson DS, Goldstein JL, Brown MS, ads. The metabolic basis of inherited disease, 5th ad. New York: McGraw-Hill, 1983:287-299. 2. Weinberg AG, Mize CE, Worthen HG. The occurrence of hepatoma in the chronic form of hereditary tyrosinemia. J Pediatr, 1976:88:434-438. 3. Hardwick OF, Dimmick JE. Metabolic cirrhosis of infancy and childhood. Perspect Pediatr Pathol, 1976;3: 103-144. 4. Stanley RJ. Liver and biliary tract. In: Lee JKT, Sagel SS. Stanley RJ, ads. Computed body tomography. New York: Raven, 1983: 172-173, 186-189. 5. Freeman MP, vici CW, Taylor KJW, Carithers AL, Brewer WH. Regener- ating nodules in cirrhosis: sonographic appearance with anatomic corre- lation. AJR 1986;146:533-536. 6. Edmondson HA, Peters RL. Tumors of the liver: pathologic features. Semin Roentgenol 1983:18:75-83 Page 8 of 9
7. Mitchell G, Faucher F, Larochelle J, Lambert M, et al. Hepatorenal tyrosinemia: shortterm results of NTBC treatment of 9 patients [abstract]. Clin Invest Med 1995; 18: A43. 8. Lindstedt S, Holme E, Lock E, et al. Treatment of hereditary tyrosinaemia type I by inhibition of 4-hydroxyphenylpyruvate dioxygenase. Lancet 1992; 340: 813-7. 9. Lindstedt S, Holme E, Lock E. Recent experience in the treatment of hereditary tyrosinemia type 1 with NTBC. First International Symposium on Hereditary Tyrosinemia; 1994 Oct 1517; Lac Delage, Quebec. Page 9 of 9