Propionic Acidemia

Some friends of mine recently had a baby who was diagnosed with Propionic Acidemia. Apparently this means that the baby cannot digest protein. The parents have talked with the doctors extensively about what they can do to help at home, life expectancy, etc., but they are consistently told that all cases are different and there’s no way to know what to do. Apparently it comes from a mutated (or recessive maybe?) gene that has to exist in both parents for the disease to appear in the child. I don’t think children with this disease live very long, nor do they develop mentally like healthy children. I think the oldest living person with the disease is 18. Any help you might provide would be greatly appreciated.Thanks in advance for your time.
Alli – Stockton, California

Dr. Greene’s Answer:

Propionic acidemia can be a devastating condition, but with careful treatment it is sometimes possible for people with the disease not only to reach adulthood successfully but even to get pregnant and deliver healthy babies!

But for parents whose children have propionic acidemia, the first weeks after the symptoms appear seem like a surreal nightmare. Rather than little bundles of joy, or fussy bundles of colic, these children are floppy and weak. Most often the children get increasingly lethargic and don’t have those wonderful, quiet, alert moments where baby and parent can connect. Not even feeding is a comfort, with vomiting and poor growth being common features. Often no one knows what the problem is, but without quick intervention, the situation can deteriorate quickly to seizures, coma, and death.

And when the diagnosis is finally made, the situation can sound even more bleak than the previous fears of the unknown. A nightmare indeed!

But a new treatment on the horizon may turn out to be a dream come true.

Inborn Error of Metabolism

Propionic acidemia is what we call an inborn error of metabolism. Our bodies use detailed blueprints (our genes) to guide the manufacture of the proteins and enzymes we need to carry out the processes of life. Errors in these genes can lead either to a lack of necessary proteins or to the accumulation of toxic substances.

Most mutations in these genes cause no problem; they are just differences that set individuals apart. But more than 100 known single-gene changes do produce disease. Each of these inborn errors of metabolism is rare, but taken as a group, the conditions are fairly common. They range from very mild to quite severe. Even some of the worst can be successfully treated with something as simple as a dietary change. Others are relentlessly fatal.

Some of my most heart-rending experiences as a physician and as a friend have been watching the devastation caused by inborn errors of metabolism.

Inborn errors of metabolism should be suspected (and often aren’t) in any child with persistent vomiting, failure to thrive, lethargy, abnormal muscle function or tone, unexplained seizures, neurological deterioration, or developmental regression-especially in the absence of obvious congenital anomalies. A family history of a similar condition, a peculiar odor, or physical changes such as a large liver or spleen should also lead one to consider inborn errors.

Propionic Acidemia: An Error in Protein Metabolism

Every time we eat food that contains protein, our bodies use a series of enzymes to break those huge foreign protein molecules into small pieces. These then become the building blocks we reassemble to form the specific human proteins we need.

In people with propionic acidemia, there is an insufficient supply of one of these enzymes (propionyl coenzyme A [CoA] carboxylase). Without the propionyl CoA carboxylase, there is a bottleneck in protein processing. Propionic acid builds up in the blood. This is known to damage the lining of small blood vessels, allowing the propionic acid to leak into the brain and nerve tissues, where it alters behavior and development. Ammonia also accumulates in the blood. This too can damage the brain. Food that is meant to nourish becomes a poison.

More Than One Disease

Propionic acidemia is really more than one disease, depending on the extent of the enzyme deficiency. In some people, the defect is complete, with the early onset of severe symptoms. At the other end of the spectrum, one man had such a mild deficiency that he didn’t develop symptoms until he was 31 years old!

There are now approximately 100 known different mutations to the propionic carboxylase gene (Mol Genet Metab. 2004 83:28). As our understanding of genetics accelerates, I expect that soon we will be able to make precise correlations between the specific genetic defect and the expected clinical course. Even now, though, we can tailor treatments to individual children while recognizing principles that apply to most children.

In general, those with intermediate levels of enzyme deficiency have symptoms that come in separate attacks when levels of protein to be digested are out of balance with the amount of enzyme available. This might be caused by a high-protein diet’s increasing the protein to be digested, or by stress or illness, decreasing enzyme production. Constipation can also trigger an attack because it increases dietary protein available for processing and because gut bacteria can produce additional propionic acid. These attacks can cause a rapid downward spiral in a child’s condition because the vomiting child with poor appetite, desperate for calories, will begin to process his own protein for food, leading to increasing levels of acid.

Laboratory findings during the acute attack reveal excess acid in the blood, low white blood cells (neutropenia), low platelets, and low blood sugar. Ammonia also accumulates in the blood. The level of ammonia often correlates with the severity of the disease, so this is measured to design and monitor treatment.

Treatment of Propionic Acidema

Treatment of acute attacks includes rehydration, correction of acid-base balance, and provision of adequate calories, often through intravenous feedings. Minimal amounts of protein should be given, and this protein should be deficient in the four amino acids that need propionyl CoA carboxylase to digest them (isoleucine, valine, threonine, and methionine). To control the possible production of propionic acid by intestinal bacteria, antibiotic therapy (such as with metronidazole) should be started promptly. Constipation should also be treated. Patients with propionic acidemia may develop carnitine deficiency, presumably as a result of urinary loss of propionylcarnitine. Administration of L-carnitine may be necessary to stop the attack.

Very ill patients with severe acidosis and elevated blood ammonia require dialysis to remove ammonia and other toxic compounds. Although infants with true propionic acidemia are rarely responsive to biotin, this compound should be administered to infants during the initial attack. It is very important in treating other errors of protein metabolism that look very similar.

Long-term treatment includes a low-protein diet (1.0-1.5 g/kg/24 hr). Synthetic proteins deficient in key amino acids (isoleucine, valine, threonine, and methionine) are used to increase the amount of dietary protein (to 1.5-2.0 g/kg/24 hr) while causing minimal change in propionic acid production. Still, natural proteins should comprise most (50-75%) of the dietary protein.

L-carnitine supplementation (50-100 mg/kg/24 hr orally) is also a part of long-term treatment. And thiamin deficiency has been shown to make propionic acidemia worse. Early vitamin supplementation is a good idea for these children-and especially when having an attack.

We used to think that the mental and developmental problems were solely a result of damage done during attacks. Recent evidence, however, suggests that damage may also occur even in the absence of attacks. Head MRI (which shows brain structure) and PET scan (which shows brain function) can be useful for following any silent progression of the disease.

Close monitoring of blood pH, amino acids, urinary content of propionate and its metabolites, and growth curves is necessary to adjust the proper balance of the diet and ensure the success of therapy. Some patients may require chronic alkaline therapy to correct low-grade chronic acidosis. Also, children with propionic acidemia are especially prone to infections. Any infection should be treated promptly.

With this type of regimen, some children do quite well, but treatment must be continued for a lifetime with conventional therapy. In two known cases, the parents believed their children to be cured. They abandoned cumbersome diet and medications, resulting in the sudden death of both children.

Long-term Outcome for Propionic Acidemia

Long-term prognosis is guarded-especially in those who develop symptoms in the first week of life. Seizures occur in about 30% of affected infants. Survival has been improving dramatically in recent years, but death may still occur during an acute attack. Normal development is possible, but most children do have some degree of permanent developmental deficit.

Strictly following a diet tailored to the child tends to improve results. But even apart from diet, outcomes vary considerably. In one family, a brother was diagnosed at 5 years of age, whereas his 13-year-old sister, with the same level of enzyme deficiency, had no symptoms at all!

The great news is that truly curing this disease-not just treating it-may be around the corner! Gene therapy is one method scientists have explored. In gene therapy, a missing or nonfunctioning gene is replaced by a new, functioning gene. In the laboratory, gene therapy for propionic acidemia has already worked (Am J Hum Genet Oct 2007). The hope is bright that within a few years the defect may be curable in humans. Successful gene therapy will not reverse brain or nerve damage but can stop any further damage from occurring-giving the child a chance to grow unfettered. Coupled with important advances in early diagnosis-possible now even before a baby is born-the potential is huge.

Auxiliary liver transplant is another strategy that has been explored for the treatment of inborn errors of metabolism. Affected children are essentially given an extra liver! The donated liver supplies enough of the missing protein to restore normal metabolism. Such transplants in children with propionic acidemia have been so successful that, in some cases, a protein-restricted diet was no longer needed.

As modern technology opens up new doors for a potential cure, one thing we do know about propionic acidemia is that the earlier the disease is detected and treated, the better. I am absolutely thrilled by the recent action of so many states to screen all newborn babies for proprionic acidemia and other genetic diseases.

The National Newborn Screening and Genetics Resource Center keeps an updated list of states and the genetic conditions they routinely look for in their newborn screen. In states where expanded newborn screening is not offered, parents can still have their babies tested by asking their doctors about testing through a private laboratory. I would encourage every family to seek newborn screening if at all possible. Early detection and action can make a major difference in children with propionic acidemia and other inborn errors of metabolism.

Note: One good place to look to learn about ongoing clinical trials is

This is NIH’s one-stop shopping area for information about clinical trials. Here you can access several databases containing facts about both public and privately supported clinical studies. Some of these studies are open to new participants, while others have already completed enrollment.

Dr. Alan Greene

Dr. Greene is a practicing physician, author, national and international TEDx speaker, and global health advocate. He is a graduate of Princeton University and University of California San Francisco.

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  1. Alison

    I just turned 40 this october and i’ve been living with propionic acidemia since birth. I live in memphis, tn. I have a job, drive a car and do all the normal things people do. Have never been in the hospital for any problems. I have to drink a formula milk and take pills but thats it.

  2. Christina

    hi there. I’m 32 ,live in Australia , Greek and have had propionic acidaemia since birth. knowing that there are people out there that can live this long and longer is amazing and inspirational. hopefully a cure comes soon. but docs say I’ve done really well for a person with P.A. so keep at it people.

    • Mariann

      My granddaugter 17 days old today (in Sweden ) has got propionic acidemia. In swedish propionsyrauri.

      What should I do?
      How am I going to think? I will think positive but it`s hard.
      She is so sick…

      Can you give me some tip how to think about the whole situation?

  3. Chloé

    29 from the uk with propionic acidemia. To my knowledge I’m the oldest in the uk x

  4. Deshae Griffin

    The oldest living person was 41 and he just was laid to rest today. Brent Burkett is his name. He was a joy. His was not discover until he was 18 months old and almost died.

  5. Jarrod B.

    Dr. Greene,
    Good early morning To You, my Name Is Jarrod From North Carolina. I Am A So-far Fighter Of Propionic Acidemia. I Was Diagnosed At The Age Of 2, back Then Not Much could Be Found Of this Disability. I Spent 3 weeks In a Coma And almost Died Once. But Anyways, dr. Told My Parents To Not Expect Me To Do Well In School Or Even Graduate High School. It Was A Hard Time But I Spent My Childhood Going In-n-out Of Hospital Not Able To Hold Food Down. I Stopped Taking My L-carnitine Medicine At The age Of 13. And only Go To Hospital once Every Few Years. It Has Been A Hard life, being Small Since I Couldnt Build Muscles Like Those Wrestlers I Watched On Television As a Child, i Still Have A Hard Time Reading Out Loud And i Havent Taken My Carnitine For Over A Decade Now. Ive gotten Kidney Stones Before, and I Have A Hard Time Holding A Normal Job but So Far thank Heavens the Tough Beginning Of childhood Tells Me To tell Others With This Disease Is “Miracles Do Happen” and I Hope To Be an Inspiration To Others. It Is Great Of This News Of A Cure For Future Generations To Come. I hope To Someday Find Out How I Am Surviving With This disability And Can I Help Others Like Me? So Families I pray You Find Hope In This Knowing Now feb. 9 2015 is A Living 28 Yr Old With This Disability. May You Be blessed

    • sue

      My grandson is 4. It’s very inspirational knowing that you are 28 and going strong. You are a true blessing. Hopefully a cure will come soon.

    • Mayda

      God bless you and give you more years to live. My daughter have GA type 1. She is almost 10 months old, but I have hope she will grow and be a healthy girl and live so many years.

    • Bilal hussain


      Both my nephews have this disease. My elder nephew (10 years) got diagnosed at around 8-9 months and was brain damaged badly in the process of finding out. Luckily my younger nephew (6 years) was diagnosed straight away when born. Now my wife is due to give birth to our third child who has 25% chances of this condition and me and my wife are carriers of this disorder.

      • Sana

        Hi Bilal,

        Similar cases from around the world do help to combat one’s pain…hope your child will be well and devoid of niece has been diagnosed with PA..when she was 3 days old..though she is stable..doctors can’t comment exactly on far so good..just wanted to know how is your younger nephew doing who was also diagnosed early..hope Allah cures all our children..

    • Ali

      Hi my brother is 7 and he suffers from proponic acidemia we are from (uk) th doctors say theres not much they can do to help him get better. I wsd wondering if you had the liver transplant?

      • Adeel

        Hi Ali. I am from the UK (Oldham, Greater Manchester) My daughter is 10 months old and has propionic acedmia. She was diagnosed at 3 weeks after having high ammonia. It would be great to get in touch

      • Chloé

        Depending on the severity there is help out there (in the uk) I’m 28 with the condition. Had to fight for my doctor to get me help after years of problems. Found one of the best doctors that knows his stuff x

        • Sana

          Hi Chloe,

          It would be helpful if you could let me know the doc details, my niece in UK has been diagnosed with PA..when she was 3 days old..yours is truly an inspirationalternative story..thanks for sharing..take care.

        • Vongai

          Hi Chloe , this is really inspirational… My daughter who is now nearly 4 was diagnosed at day 3. We have been in and out of hospital especially first two years… She is now much stable but had has global developmental delay… could you please share details of your specialist, we are also in the U.K. … she is under Great Ormandy Street Hospital …


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