Medical Care
Since the development of screening methods for succinylacetone, with the ensuing application to newborn screening, many patients are being detected prior to clinical decompensation, thus enabling initiation of treatment with nitisinone (NTBC), which has become the medical therapy of choice after extensive, worldwide experience. [17] Additional experience with NTBC therapy has shown a direct correlation between age of initiation and subsequent clinical course.
It is possible to use a submitted blood spot for monitoring succinylacetone levels periodically, in order to adjust NTBC and dietary therapies. [18]
Most patients with tyrosinemia who are not diagnosed at birth are so ill at the time of presentation that inpatient treatment is mandatory.
Direct medical therapy is aimed at the acute hepatic decompensation and coagulopathy from the outset. Replenishment of depleted coagulation factors may be essential to prevent exsanguination. After stabilization, nitisinone should be started.
Nutritional treatment should be designed to minimize the phenylalanine-tyrosine load to only essential requirements.
Surgical Care
If the critically ill child can be sufficiently stabilized by medical means, surgery has no role.
Liver transplantation is the treatment of last resort (eg, the development of severe cirrhosis or hepatic tumor). [19]
Pharmacologic Therapy
Prior to the introduction of medications for the treatment of tyrosinemia, liver transplantation was the only effective treatment. Nitisinone (Orfadin) was the first drug approved to treat hereditary tyrosinemia type I, along with dietary restriction of tyrosine and phenylalanine. Orfadin has been available in capsule form since January 2009 in oral suspension form since April 2016. The tablet formulation of nitisinone (Nityr) was FDA-approved in July 2017. Unlike Orfadin capsules, which require refrigeration, Nityr may be stored at room temperature. For patients who are unable to swallow the tablet, Nityr may be dissolved to make an oral liquid or crushed and mixed in applesauce.
An open-label study of 207 patients (aged 0-21.7 y; median age, 9 mo) showed a dramatic improvement in overall survival for patients younger than 2 months who presented with hereditary tyrosinemia type I and who were treated with nitisinone and dietary restriction, as compared with historical control subjects (29% vs 88% survival probabilities at 2 and 4 y). [20] A more recent study has shown very positive long-term theraputic and safety assessments. [21] Nitisinone must be used in conjunction with diet restriction of the amino acids tyrosine and phenylalanine. Treatment with nitisinone and dietary management should begin as soon as possible after the diagnosis is confirmed. There is recent evidence that tyrosine tolerance tends to increase slightly with age, although this dos not remove the need for close monitoring. [22]
Consultations
Consider obtaining consultations from the following specialists:
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Biochemical geneticist
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Hepatologist or gastroenterologist
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Hematologist
Diet
All children should be prescribed a low-phenylalanine low-tyrosine diet designed to meet their needs for growth without providing excesses of these amino acids.
Only a highly experienced nutritionist working with a biochemical geneticist can properly oversee the nutritional regimen.
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Tyrosine
