Conditions Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) is a condition in which the body is unable to process and remove the waste, ammonia. It considered an amino acid condition because, ammonia, is produced when the body breaks down proteins in food into their basic building blocks (amino acids). When the body’s process for removing waste is disrupted, dangerous amounts of ammonia begin to build up in the blood. If left untreated, this can result in developmental delay, learning disabilities, or stiffness caused by abnormal tensing of muscles (spasticity). Early detection through newborn screening and treatment can prevent many of the serious symptoms and outcomes of HHH.
Condition Type
Other Disorders
Frequency
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) is a very rare disorder. Fewer than 100 affected individuals have been reported worldwide.
Also known as
- HHH
- Mitochondrial Ornithine Carrier
- Ornithine Translocase Deficiency
- Hyperornithinemia-hyperammonemia-homocitrullinemia syndrome
- Triple H syndrome
Follow-Up Testing
Your baby’s doctor may ask you if your baby is showing any of the signs of HHH (see Early Signs below). If your baby has certain signs, your baby’s doctor may suggest starting immediate treatment.
If your baby’s newborn screening result for hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) was out of the normal range, your baby’s doctor or the state screening program will contact you to arrange for your child to have additional testing. It is important to remember that an out-of-range screening result does not necessarily mean that your child has the condition. An out-of-range result may occur because the initial blood sample was too small or the test was performed too early. However, as a few babies do have the condition, it is very important that you go to your follow-up appointment for a confirmatory test. Because the harmful effects of untreated HHH can occur soon after birth, follow-up testing must be completed as soon as possible to determine whether or not your baby has the condition.
Follow-up testing will involve checking your baby’s urine and blood samples for signs of HHH. Harmful amounts of certain substances build up in the body when a child has an amino acid condition, so measuring the amounts of these substances in your baby’s body can help doctors determine if your baby has the condition. High amounts of ammonia, ornithine and homocitrulline in the blood, and high levels of orotic acid in the urine may indicate that your baby has HHH. Your baby’s doctor may want to confirm the diagnosis with clinical genetic testing.
About Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome
Early Signs
Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) varies widely in its severity and age of onset. Some babies develop signs of HHH shortly after birth. Other individuals with HHH may not show any signs or symptoms until later in life. Later onset forms of HHH are usually less severe than those that develop in infancy.
Signs of HHH include:
- Tiredness
- Muscle stiffness (spasticity)
- Poorly controlled body temperature or breathing
- Refusal to eat
- Vomiting
- Developmental delays
- Slowed growth
- Seizures (also known as epilepsy)
- Problems with Coordination
Many of these signs may occur when your baby eats foods or formula that their body cannot break down. They can be triggered by long periods of time without eating, illnesses, and infections.
If your baby shows any of these signs, be sure to contact your baby’s health care provider immediately.
Treatment
Dietary treatments:
Your baby may need to follow a low-protein diet to avoid certain foods that they cannot break down. A dietician or nutritionist can help you plan the appropriate diet for your child’s healthy growth.
Your baby’s doctor might also recommend special formulas and foods for children with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH). These formulas will likely need to continue through adulthood.
Supplements and Medications:
Your baby’s health care provider may prescribe certain supplements or medications to help your baby’s body get rid of excess ammonia. Everyone has some ammonia is their blood, but high levels can be toxic.
Expected Outcomes
Babies who are treated early for hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) can have healthy growth and development. This is why newborn screening for HHH is so important. Some children still have high ammonia levels in their blood even with treatment. These individuals may need to seek treatment in a hospital to remove the ammonia from their blood. It is important to identify and treat HHH early because children who do not receive treatment for HHH are at risk for learning disabilities, seizures, brain damage, or coma.
Causes
When we eat food, our bodies break down proteins into a form that can be used by our cells. During this process, a waste product, called ammonia, is produced. Ammonia is processed and removed from the body through the action of several different enzymes. In hyperornithinemia-hyperammonemia-homocitrullinuria Syndrome (HHH), the enzyme ornithine translocase is not working correctly.
Babies with HHH either do not make enough or make non-working ornithine translocase. When ornithine translocase does not work correctly the body cannot remove ammonia through the urine. This causes a dangerous build up of ammonia in the body.
HHH is an autosomal recessive genetic condition. This means that a child must inherit two copies of the non-working gene for HHH, one from each parent, in order to have the condition. The parents of a child with an autosomal recessive condition each carry one copy of the non-working gene, but they typically do not show signs and symptoms of the condition. While having a child with HHH is rare, when both parents are carriers, they can have more than one child with the condition. Learn more about autosomal recessive inheritance.
Support for Hyperornithinemia-Hyperammonemia-Homocitrullinuria Syndrome
Support Services
Support groups can help connect families who have a child or other family member affected with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) with a supportive community of people who have experience and expertise in living with the condition. These organizations offer resources for families, affected individuals, health care providers, and advocates.
Accessing Care
Work with your baby’s doctor to determine the next steps for your baby’s care. Your baby’s doctor may help you coordinate care with a doctor specializing in metabolism, a dietician who can help plan your child’s specialized diet, and other medical resources in your community. Depending on the signs and symptoms your child experiences, your baby’s doctor may work with other doctors who specialize in treating the liver or brain. Some children with hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) have developmental delays. If you think that your baby is not meeting their developmental milestones, ask your baby’s doctor about the next steps in accessing a developmental evaluation and care.
Because HHH is a genetic condition, you may want to talk with a genetics specialist. A genetic counselor or geneticist can help you understand the causes of the condition, discuss genetic testing for HHH, and understand what this diagnosis means for other family members and future pregnancies. Speak with your baby’s doctor about getting a referral. The Clinic Services Search Engine offered by the American College of Medical Genetics and Genomics (ACMG) and the Find a Genetic Counselor tool on the National Society of Genetic Counselors (NSGC) website are two good resources for you or your baby's health care provider to use to identify local specialists.
Families' Experiences
At this time we have not located a family story for this particular condition. If your family is affected by hyperornithinemia-hyperammonemia-homocitrullinuria syndrome (HHH) and you would like to share your story, please contact us so other families may learn from your experience.
References & Sources
Visit MedlinePlus Genetics for more condition information
Visit NIH Rare Diseases Clinical Research Network(RDCRN) for more information on urea cycle disorders
ACT Sheets
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