Hereditary tyrosinemia type 1 (HT-1) is a rare genetic disorder that affects the body's ability
to break down the amino acid tyrosine. It is also known as tyrosinemia type I or hepatorenal
tyrosinemia. This condition is caused by a deficiency of the enzyme fumarylacetoacetate
hydrolase (FAH), which is involved in the final step of tyrosine metabolism.
HT-1 is inherited in an autosomal recessive manner, which means that an affected individual must
inherit two copies of the mutated gene (one from each parent) to develop the condition. The gene
responsible for HT-1 is called FAH, and mutations in this gene lead to a reduced or absent
production of the FAH enzyme.
Without FAH, toxic by-products called succinyl acetone and succinyl acetoacetate build up in the
body, causing damage to the liver, kidneys, and other organs. The liver is particularly
affected, leading to liver dysfunction and the risk of developing liver cancer.
Symptoms
If left untreated, HT-1 can be life-threatening. However, with early diagnosis and
prompt treatment, the prognosis can be significantly improved:
Poor weight gain and growth failure
Jaundice (yellowing of the skin and eyes)
Enlarged liver and spleen
Liver dysfunction, which can lead to liver failure
Renal tubular dysfunction, leading to Fanconi syndrome (a kidney disorder)
Increased risk of liver cancer (hepatocellular carcinoma)
Neurological symptoms (in some cases)
Diagnosis
The diagnosis of tyrosinemia type 1 is made based on a combination of factors, including:
The patient's symptoms, such as growth failure, jaundice, and liver enlargement.
Blood tests that show high levels of tyrosine and other metabolites.
Urine tests that show high levels of succinylacetone, a byproduct of tyrosine metabolism.
Genetic testing to look for mutations in the FAH gene.
Treatment
The primary treatment for HT-1 involves a strict low-protein diet and the medication Nitisinone
(NTBC). Nitisinone inhibits an earlier step in tyrosine metabolism, reducing the production of
toxic byproducts. This medication, along with a carefully controlled diet, helps manage the
symptoms and prevents further liver damage.
In some cases, liver transplantation may be necessary if liver failure occurs or if there is a
risk of liver cancer. Transplantation can restore liver function and prevent complications
associated with HT-1.
It is important for individuals with HT-1 to receive ongoing medical monitoring, including
regular blood tests to monitor liver and kidney function. Long-term management aims to prevent
complications, maintain nutritional balance, and ensure optimal growth and development.
Early Diagnosis and Treatment
Early detection through new-born screening programs can
significantly improve outcomes. Seek prompt medical
attention if you notice symptoms such as failure to thrive,
jaundice, or liver symptoms in your child.
Comply with the prescribed treatment plan, which typically
involves a combination of
medication, dietary restrictions, and regular monitoring.
Adhere to a Low-Tyrosine and Phenylalanine Diet
Work closely with a registered dietitian experienced in
metabolic disorders to develop a tailored diet plan.
Strictly adhere to a low-protein diet, limiting foods rich
in tyrosine and phenylalanine, such as meat, dairy products,
nuts, and legumes.
Opt for specialized medical formulas recommended by your
doctor to ensure proper nutrition.
Medication Compliance
Administer medication as prescribed by your doctor,
typically including nitisinone (NTBC) and other supportive
therapies.
Regularly monitor blood levels of NTBC and tyrosine to
optimize dosing and maintain therapeutic ranges.
Report any adverse effects or concerns to your doctor
promptly.
Regular Medical Follow-up
Schedule regular check-ups and follow-up appointments with
your doctor to monitor liver and kidney function, growth,
and overall health.
Stay informed about the latest research, treatment options,
and advancements in HT-1 management.
Emotional and Social Support
Seek support from patient organizations, support groups, or
online communities to connect with individuals facing
similar challenges.
Consider counseling or therapy to address emotional
well-being, as living with a chronic condition can be
emotionally demanding.
Remember that siblings of patients with Tyrosinemia type I
may also require emotional support. The condition can impact
their lives and bring about feelings of confusion,
resentment, or guilt. Provide age-appropriate information to
siblings and encourage them to express their feelings and
concerns
Recognize and celebrate the milestones and achievements of
the patient and their siblings. Tyrosinemia type I may
present unique challenges, but it's important to highlight
the strengths and successes of each family member. This can
boost their morale and foster a positive outlook.
Neglecting Medication or Diet
Avoid skipping or altering medication doses without
consulting your doctor.
Do not deviate from the prescribed diet, as it plays a
crucial role in managing HT-1 symptoms.
Unsupervised Dietary Modifications
Do not attempt to modify the dietary restrictions or
introduce new foods without professional guidance, as it may
disrupt the metabolic balance.
Delaying or Ignoring Symptoms
Promptly report any new or worsening symptoms to your
doctor, such as abdominal pain, vomiting, fatigue, or
changes in urine colour.
Do not ignore signs of liver or kidney dysfunction
(jaundice, poor weight gain, enlarged liver and spleen, a
tendency to bleed easily, dehydration, and weakness) as
early intervention is crucial for preventing complications.
Noncompliance with Follow-up Visits
Avoid missing or postponing scheduled medical appointments,
as regular monitoring is essential for evaluating treatment
efficacy and detecting potential issues.
Frequently Asked Questions
Hereditary Tyrosinemia Type 1 (HT-1) is a rare genetic disorder that affects the
breakdown of the amino acid tyrosine. It is caused by a deficiency of the enzyme
fumarylacetoacetate hydrolase (FAH), which leads to the accumulation of toxic
metabolites in the liver, kidneys, and other organs.
The symptoms of HT-1 can vary, but they often include liver dysfunction, such as
jaundice, poor weight gain, enlarged liver and spleen, and a tendency to bleed
easily. Other symptoms may include kidney problems, rickets (weakening of the
bones), and a cabbage-like odor to the urine.
HT-1 is usually diagnosed through newborn screening programs that test for
elevated levels of tyrosine in the blood. Confirmation of the diagnosis is done
through genetic testing to identify mutations in the FAH gene. Additional tests,
such as liver function tests, urine analysis, and imaging studies, may be
performed to assess the extent of organ damage.
The primary treatment for HT-1 is a low-protein diet, which restricts the intake
of tyrosine and phenylalanine. This diet helps reduce the production of toxic
metabolites. Medications such as nitisinone (NTBC) may also be prescribed to
block the formation of toxic metabolites. In some cases, liver transplantation
may be necessary if the disease progresses and causes severe organ damage.
While there is currently no cure for HT-1, early diagnosis and appropriate
treatment can effectively manage the condition and prevent or minimize
complications. With lifelong adherence to a low-protein diet, medication, and
regular medical follow-ups, individuals with HT-1 can lead relatively normal
lives.
HT-1 is an autosomal recessive disorder, which means that both parents must pass
on a mutated copy of the FAH gene for a child to develop the condition. If both
parents are carriers of the gene mutation, there is a 25% chance of their child
inheriting HT-1.
Yes, HT-1 can affect children and adults differently. In infants and young
children, HT-1 typically presents as a severe and rapidly progressing condition.
It often becomes apparent within the first few months of life, and if left
untreated, it can lead to liver failure, kidney dysfunction, and neurological
problems. In contrast, adults with HT-1 may present with milder symptoms and a
more chronic course of the disease. Some individuals may remain undiagnosed
until adulthood, as their symptoms may be less severe or nonspecific.
Yes, individuals with HT-1 typically have specific dietary restrictions to
manage their condition effectively. Strictly adherence to a low-protein diet,
limiting foods rich in tyrosine and phenylalanine, such as meat, dairy products,
nuts, and legumes is required.
Yes, individuals with HT-1 can have children. However, since HT-1 is an
autosomal recessive disorder, there is a risk of passing on the mutated FAH gene
to their children. Genetic counseling is recommended to assess the risk and
discuss options for family planning.
Yes, like any medical condition, HT-1 can potentially be misdiagnosed. HT-1 is a
rare genetic disorder that affects the metabolism of the amino acid tyrosine. It
is caused by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH).
Misdiagnosis can occur for various reasons, including the rarity of the
condition, the presence of overlapping symptoms with other disorders.
Without treatment, HT-1 can lead to progressive liver disease, liver failure,
and an increased risk of liver cancer. It can also affect the kidneys, leading
to renal tubular dysfunction and kidney failure. Bone problems, such as rickets,
may occur due to impaired vitamin D metabolism. Regular monitoring and adherence
to the treatment plan are crucial to prevent or manage these complications.
With proper management, including adherence to dietary restrictions, regular
monitoring, and appropriate medical care, individuals with HT-1 can live
relatively normal lives. Yes, patients with HT-1 can typically go to school, but
their educational experience may require some accommodations and considerations.
Similarly, adults with HT-1 can typically work, but it is important to take into
consideration their health status and any limitations they may have.
Patients with HT-1 are generally advised to avoid consuming alcohol. The liver
is primarily responsible for metabolizing alcohol, and individuals with HT-1
often have liver dysfunction or are at risk of developing liver disease.
Consuming alcohol can further burden the liver and worsen liver function,
potentially leading to complications or exacerbating existing symptoms
associated with HT-1.
Patients with HT-1 are not inherently more prone to infections compared to the
general population. However, the liver dysfunction associated with HT-1 can have
indirect effects on the immune system, which may increase the risk of infections
in some cases. It is important for individuals with HT-1 to take precautions to
minimize the risk of infections. This includes practicing good hygiene,
maintaining a balanced and nutritious diet, staying up to date with
vaccinations, and following their doctor's recommendations regarding treatment
and monitoring of the disease.
No, HT-1 is not contagious. It is not transmitted through casual contact or
exposure to an affected individual. It is purely a genetic condition and cannot
be passed from person to person like an infectious disease.
References
Larochelle J, Alvarez F, Bussières JF, et al. Effect of nitisinone (NTBC) treatment on the clinical course of hepatorenal tyrosinemia in Québec. Mol Genet Metab. 2012;107(1-2):49-54.
van Ginkel WG, Jahja R, Huijbregts SC, et al. Long-term follow-up and outcome of liver transplantation for tyrosinemia type 1: a registry study. Liver Transpl. 2017;23(6):796-805.
Chinsky JM, Singh R, Ficicioglu C, et al. Diagnosis and treatment of tyrosinemia type I: a US and Canadian consensus group review and recommendations. Genet Med. 2017;19(12).
Lamireau T, Dubois S, Girard M, et al. Expert opinion on the management of hereditary tyrosinemia type 1. Ann Transl Med. 2019;7(22):690.
Masurel-Paulet A, Poggi-Bach J, Rolland MO, et al. NTBC treatment in tyrosinaemia type I: long-term outcome in French patients. J Inherit Metab Dis. 2008;31(1):81-87.
Van Ginkel WG, Jahja R, Huijbregts SC, et al. Health-related quality of life and neurodevelopmental outcomes in children with tyrosinemia type 1 receiving nitisinone: a multinational natural history study. Orphanet J Rare Dis. 2019;14(1):135.
Caregiver /
Patient 
