Is it tyrosinemia_?
Ira Shah
Medical Sciences Department, Pediatric Oncall, Mumbai, India

Address for Correspondence: Dr Ira Shah, 1, B Saguna, 271, B St Francis Road, Vile Parle {W}, Mumbai 400056

Clinical Problem :
A 2½ years old boy born of third degree consanguineous marriage presented with bulky frothy stools for 6 months and low hemoglobin, abdominal distension for 4 months for which he had received a blood transfusion 4 months ago. Parents also noticed bow legs for past 3 months. There was no jaundice, or polyuria. For the anemia, a bone marrow aspiration had been done that was normal. His elder brother was on treatment for leukemia. Currently, the patient was on iron, calcium and vitamin D supplements. His birth was uneventful and milestones were appropriate for age. On examination, height was 86 cm, weight was 13 kg. He had rickets with genu varus and hepatosplenomegaly. Investigations showed hemoglobin 10.9 gm, dl, white cell count 9,100 cells, cumm, platelets 91,000, cumm, bilirubin 1.4 mg, dl {direct 0.9 mg percent} SGOT 116 IU, L, SGPT 85 IU, L, total proteins 4.6 gm, dl, albumin 2.8 gm, dl, prothrombin time {PT} 21.4 sec, partial thromboplastin time {PTT} 25.6 sec, alkaline phosphatase 2120 IU, L, pH 7.436 with bicarbonate 18.0 mmol, L and alpha feto protein 8019 IU, ml. Ultrasound abdomen showed splenomegaly, nephromegaly {right kidney = 8.2 x 4.7 cm, left kidney = 8.7 x 5.8 cm} with doppler showing intrahepatic collaterals. Urine organic acids showed increased phenylalanine, lactate, glycerate, fructose, tyrosine, 4-hydroxyphenyl lactate and 4-hydroxyphenyl pyruvate suggestive of tyrosinemia though urine succinyl acetone was normal. Esophageogastroscopy showed varices in body, fundus and antrum of stomach. HIV Elisa, HBsAg and Hepatitis B were negative. He was treated with Vitamin K, folic acid, bicarbonate supplements, propanolol and diet restricted in tyrosine and phenylalanine.

Question :
Can this be tyrosinemia with normal urine succinyl acetone_?

Expert Opinion :
Type I tyrosinemia is an autosomal recessive disorder affecting the tyrosine degradation pathway and leads to liver failure, Fanconi syndrome and, or rickets. {1} It is caused by a mutation in the gene encoding for the fumarylacetoacetate hydrolase {FAH} enzyme. Deficiency of this enzyme causes intracellular accumulation of fumarylacetoacetate {FAA} which is rapidly degraded to succinylacetone {SA} which is found in urine of patients with this condition. {2} Diagnosis of type 1 tyrosinemia is based on the presence of liver disease, kidney disease and, or rickets, increased tyrosine and methionine in plasma and presence of SA in urine and blood. {2} However, diagnosis can be suspected on basis of persistent asymptomatic firm hepatomegaly, mildly deranged liver functions, very high alpha-fetoprotein levels, high tyrosine levels in plasma with urinary aminoaciduria as was done in our patient. {4} Thus, we treated him as tyrosinemia. 2-{2-nitro-4-tri fluoromethylbenzoyl}-1,3-cyclohexanedione {NTBC} could not be started in this patient due to non-availability. Six months later, his bilirubin rose to 2.7 mg, dl and by the year end, he had cyanosis due to hepatopulmonary syndrome. By now, his urine SA had increased. He was advised regarding liver transplant but subsequently lost to follow up.

1. Scott CR. The genetic tyrosinemias. Am J Med Genet C Semin Med Genet.2006` 148: 121-126.
2. Cassiman D, Zeevaert R, Holme E, Kvittingen EA, Jacken J. A novel mutation causing mild, atypical fumarylacetoacetase deficiency {Tyrosinemia type 1}` a case report. Orphanet J Rare Disease. 2009` 4: 28.

Correct Answers :  yes 80%
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