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PubMed This is a summary of 14 peer-reviewed journal articles Updated
Pediatrics

Understanding Histidinemia: A Guide for Parents

At a Glance

Histidinemia is a benign metabolic variant, not a dangerous disease. Caused by an underactive enzyme, it leads to high histidine levels but does not affect intelligence or development. Decades of research confirm that children with histidinemia do not need special diets or treatment to thrive.

It is completely normal to feel a wave of fear, confusion, or even shock when you receive a call saying your newborn’s screening test came back positive for a metabolic genetic disorder [1]. For most parents, those words sound incredibly heavy, as if the healthy future you imagined for your child has suddenly shifted [1].

The most important thing to know right now is that histidinemia is almost universally regarded by modern medicine as a benign metabolic variant, not a dangerous disease [2][2]. While the terminology sounds serious, the reality for the vast majority of children is a perfectly normal, healthy life [2].

What is Histidinemia?

To understand histidinemia, it helps to think of the body as a chemistry lab. Your baby’s body uses enzymes (specialized proteins) to break down the food they eat. One of the building blocks of protein is an amino acid called histidine [3].

In children with histidinemia, a specific enzyme called histidase is either missing or not working at full capacity [3]. Because the “recycling” process for this amino acid is blocked, histidine levels build up in the blood and urine [2].

Why Doctors Aren’t Worried

In the 1970s and 80s, histidinemia was included in many newborn screening programs because doctors worried that high histidine levels might cause developmental delays [4]. However, massive, decades-long studies changed everything.

Researchers in places like Japan and Quebec followed thousands of children with histidinemia for over 20 years [2][4]. They discovered:

  • No Difference in Intelligence: Children with histidinemia had the same IQ scores and developmental progress as children without it [2].
  • No Need for Treatment: Even children who were not put on a special diet did just as well as those who were [2].

If It’s Benign, How Was My Baby Diagnosed?

Because the condition didn’t cause health problems, Japan stopped routine screening for it in 1993, and it is not included in the United States’ Recommended Uniform Screening Panel (RUSP) [4][5].

You might be wondering: How did my baby test positive if they don’t screen for it anymore? Today, histidinemia is usually detected because your state or country uses an expanded metabolic screening panel that still catches it, or it appears as an incidental finding when doctors are screening for other conditions [5].

Histidinemia is one of the most common “biological quirks” discovered through screening:

  • In Japan: Approximately 1 in 8,000 newborns [4].
  • In Quebec, Canada: Approximately 1 in 8,000 newborns [4].
  • In the U.S. and Europe: Approximately 1 in 20,000 to 1 in 30,000 newborns [4].

Navigating the “Vulnerable Child” Feeling

It is common for parents to feel protective or “on edge” after a screening scare [1]. This is sometimes called vulnerable child syndrome, where parents continue to see a healthy child as fragile even after being told everything is okay [1].

Remember that your baby is the same child they were before the test results arrived. Modern science has moved away from treating histidinemia as a “disease” because the evidence shows that these children grow, learn, and thrive just like their peers [2]. While your doctor may suggest a follow-up test to confirm the levels, this is usually a standard precaution.

Explore more about Histidinemia:

01

The Biology of Histidinemia and How It Is Diagnosed

Learn about the biology and diagnosis of histidinemia in newborns. Understand HAL gene variations, inheritance, high histidine levels, and confirmatory testing.

02

Symptoms, History, and the "Scary Internet Search"

Learn why a histidinemia diagnosis shouldn't scare you. Discover the history behind outdated myths about speech delays, IQ, and why it's considered benign.

03

Standard of Care and Living a Normal Life

Learn the standard of care for histidinemia. Understand why a special diet is not needed, how routine monitoring works, and why your child can live a normal life.

Common questions in this guide

Is histidinemia a dangerous genetic disease?
Modern medicine universally considers histidinemia to be a benign metabolic variant rather than a dangerous disease. Extensive long-term studies have shown that children with this condition live healthy lives and have normal intelligence and development.
What causes high histidine levels in newborns with histidinemia?
High histidine levels are caused by a missing or underactive enzyme called histidase. Without enough of this enzyme working properly, the body cannot fully break down the amino acid histidine from food, causing it to build up in the blood and urine.
Why did my baby test positive if histidinemia isn't routinely screened for?
Your baby likely tested positive because your state or country uses an expanded newborn metabolic screening panel. Although routine screening for histidinemia was largely discontinued when it was proven benign, it frequently appears as an incidental finding on these broader tests.
Does my baby need a special diet or treatment for histidinemia?
No, decades of medical research have proven that children with histidinemia do not require any special diet or medical treatment. Children who consume a standard diet develop and thrive just as well as those placed on restricted diets.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Does our state or country still routinely screen for histidinemia, or was this an expanded screen?
  2. 2.Can you explain why histidinemia is now considered a 'benign variant' rather than a disease?
  3. 3.What were our baby’s specific histidine levels, and how do they compare to the typical 'benign' range?
  4. 4.Are there any specific symptoms or developmental milestones we should watch for, even though most kids do fine?

Questions For You

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References

References (5)
  1. 1

    Absorbing it all: A meta-ethnography of parents' unfolding experiences of newborn screening.

    White AL, Boardman F, McNiven A, et al.

    Social science & medicine (1982) 2021; (287()):114367 doi:10.1016/j.socscimed.2021.114367.

    PMID: 34534781
  2. 2

    The self-assembly of L-histidine might be the cause of histidinemia.

    Ajikumar A, Premkumar AKN, Narayanan SP

    Scientific reports 2023; (13(1)):17461 doi:10.1038/s41598-023-44749-5.

    PMID: 37838762
  3. 3

    Spiropyran-modified upconversion nanocomposite as a fluorescent sensor for diagnosis of histidinemia.

    Su J, Li Y, Gu W, Liu X

    RSC advances 2020; (10(45)):26664-26670 doi:10.1039/d0ra03711g.

    PMID: 35515791
  4. 4

    Newborn Screening in Japan-2021.

    Tajima T

    International journal of neonatal screening 2022; (8(1)) doi:10.3390/ijns8010003.

    PMID: 35076455
  5. 5

    Implementation of Newborn Screening for Conditions in the United States First Recommended during 2010-2018.

    Singh S, Ojodu J, Kemper AR, et al.

    International journal of neonatal screening 2023; (9(2)) doi:10.3390/ijns9020020.

    PMID: 37092514

This page provides educational information about histidinemia in newborns. It is not a substitute for professional medical advice, and you should always discuss newborn screening results with your pediatrician.

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