One of the X chromosome-linked disorders is ornithine transcarbamylase deficiency in the urea cycle. This disorder results in increased ammonia and glutamine in the blood. Accumulation of these metabolites without treatment causes brain edema, which often progresses to coma and death. This study describes a 5-year-old girl with ornithine transcarbamylase deficiency who presented with hyperammonemic encephalopathy that was successfully treated with an orthotropic liver transplant. Recently, liver transplant has been introduced as an alternative treatment for patients with ornithine transcarbamylase deficiency.

Key words : Hyperammonemia encephalopathy, Liver transplant, Shiraz, Urea cycle disorders

Introduction

One of the X chromosome-linked disorders is ornithine transcarbamylase (OTC) deficiency in the urea cycle. This disorder results in increasing ammonia and glutamine in the blood. The accu­mulation of these metabolites without treatment causes brain edema, which often progresses to coma, neurologic deficit, and death.^1-3

Prolonged treatment includes limited use of proteins and use of nitrogen scavengers. In selected cases, liver transplant is performed to improve growth and development and to prevent hyper­ammonemia. Ornithine transcarbamylase deficiency can present at any age. For patients with complete deficiency, severe and neonatal onset, liver transplant is usually performed within 6 months of age to avoid more hyperammonemia and neurodevelopmental worsening. Patients with partial OTC deficiency present due to a stressful experience at almost any time of life.⁴

Urea cycle enzymes generate in the liver; therefore, a liver transplant is a good alternative for patients with OTC deficiency. In reported cases of persons who have undergone a liver transplant, serum ammonia levels return to normal quickly after a transplant, and then serum amino acid profile and urinary orotic acid return to their normal ranges.³ Several studies have reported the significant role of liver transplant in controlling metabolic com­plications, hyperammonemia encephalopathy, and protection of neurologic function. If a liver transplant is performed too late, an established neurologic deficit will not improve.⁵

In this case report, we discuss a girl with OTC deficiency who underwent a liver transplant 4.5 years after diagnosis of her disease.

Case Report

A girl with an uncomplicated gestation and uneventful delivery presented with vomiting, lethargy, and poor feeding at about 6 weeks of age. She was treated for sepsis with intravenous antibiotics but had no response. She then underwent a complete laboratory work-up, and hyperammonemia was detected as being due to a lack of acidosis. She was suspected of having urea cycle disorders, and after additional investigations (eg, genetic tests), OTC deficiency was confirmed. Her ammonia level was elevated but was controlled for several months by protein restriction and pharmacologic therapy. Despite a restricted protein diet and treatment with arginine 200 mg/kg/day, sodium benzoate 250 mg/kg/day, and phenyl­butyrate 250 mg/kg/day and also carnitine supplements, she had episodes of hyperammonemic encephalopathy ranging from lethargy to coma.

She was then referred to Shiraz Liver Trans­plant Center in April 2014 at the age of 5 years. On admission, she was emaciated and mildly hypotonic with poor eye-to-eye contact. Also, she needed help walking owing to an ataxic gait. A neuropsychiatric examination revealed no significant findings. Before having the transplant, her body weight was 14 kg. Urinary orotic acid excretion was 978.3 mg/g creatinine (reference range < 5), blood urea nitrogen was < 5 mg/dL, and her liver enzymes were normal. The results of an abdominal ultra­sonography, a brain magnetic residence imaging scan, and an electroencephalogram were normal.

On June 7, 2014, she underwent partial living-related orthotropic liver transplant from her mother with matched blood group, and she received left lateral segment using a piggyback method. The bile duct was reconstructed by duct-to-duct method. After induction with antithymocyte globulin, tacrolimus (FK 506) and steroids were used as immuno­suppressants. Plasma ammonia levels returned to a normal range 5 days after surgery.

The main complications immediately after transplant were portal vein thrombosis on the day of surgery (which was explored, and a thrombectomy was successfully done). She had one episode of convulsion after surgery, but a neurologic exam­ination and an electroencephalogram were normal. According to the neurology pediatrician’s report, her convulsion was due to adverse effects from drugs. Also, a bowel perforation occurred 3 weeks after the operation. An exploration was done and the perforation was repaired. One month after her c, she was discharged home on an unrestricted diet, and sodium benzoate, phenyl­butyrate, and arginine were discontinued gradually. At 1.5-year follow-up, she is doing well, without protein restriction, and she has normal development. Liver function tests are normal with 1 mg twice daily of tacrolimus.

Discussion

Liver enzyme deficiency results in certain metabolic disorders, without significant influence on liver function, but affected patients present with extrahepatic toxicity owing to toxic intermediates.⁶ The liver is the main source of urea cycle enzymes. If patients with OTC deficiency do not respond to medical and conservative therapy, liver transplant is a good alternative for patients with the missing enzyme. Metabolic disorders treated with liver transplant have better results than shown in individuals with primary liver disease. The survival rate of these disorders after a liver transplant is better than the structural liver disease.⁷ Studies report a 5-year survival rate for children with OTC deficiency after a liver transplant of more than 90%, and this treatment is the only way to manage OTC deficiency completely.^8,9 Therefore, a liver transplant is a successful treatment for patients with severe hyperammonemia caused by OTC deficiency.

In this study, we report the first experience of treating a case of OTC deficiency with a liver transplant in Shiraz. The patient with OTC deficiency had satisfactory outcome after liver transplant.

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