Glutaric Aciduria Type 1: Symptoms Mimic Shaken Baby Syndrome

Case Note Hannan:
On July 22, 1991, 8-month-old Kelly Hannan fell and hit her head. She was taken to the doctor, lethargic and limp. From there she was rushed to Denver Children’s Hospital where a CT scan revealed bleeding in her brain and eyes. The doctors diagnosed Shaken Baby Syndrome. Kelly was placed in a foster home while Denver Social Services and the police investigated. More than three months later, Kelly was diagnosed with Glutaric Aciduria Type 1. The Hannans filed a lawsuit against the individuals and institutions that had handled the case, claiming that the delayed diagnosis had prevented proper treatment. They settled out of court for an undisclosed sum and are not allowed to talk about the case (1).
Case Note Sandoval:
On December 16, 2001, baby Michael Sandoval was unresponsive. His mother Lisa called 911 and Michael was rushed to the hospital. Doctors suspected that Lisa had shaken her son violently, and Child Protective Services believed that Michael’s father had failed to stop the abuse. Michael and two older siblings were removed from the home and an investigation was launched. Four days later, Michael was diagnosed with Glutaric Aciduria Type 1 (2). However, it still took approx. 3 weeks for the Sandovals to be cleared of the charges.
What is Glutaric Aciduria?

Glutaric Aciduria, also called Glutaric Acidemia, is a relatively rare inherited error of metabolism. There are two types: 1 and 2. The symptoms of type 1 are remarkably similar to those seen in Shaken Baby Syndrome and often include subdural hematoma (bleeding in the brain) and retinal hemorrhage (bleeding in the eyes). A number of cases have initially been misdiagnosed as child abuse with the result that proper treatment was delayed (3,4,5,6,7). Sadly, many doctors continue to be unaware that an organic condition can mimic Shaken Baby Syndrome. In one case, the doctor testified that she did not screen for the disorder because it was “unlikely.” But “unlikely” is not the same as “beyond a reasonable doubt.” Caretakers who are falsely accused of shaking an infant should insist that Glutaric Aciduria Type 1 be screened out as a possible cause of the injuries.

History of Glutaric Aciduria type 1 (GA-1)

The condition was first discovered by Dr. Stephen Goodmen at the University of Colorado in 1975(8). He published about a year after Dr. John Caffey’s article “The Whiplash Shaken Infant Syndrome”(9). Since then, several hundred articles have appeared in the medical literature.

As early as May 1977, Gregersen et al. recommended screening for organic aciduria in all children with unexplained neurological symptoms (10). In January 1979, Whelan et al. wrote: “any infant with central nervous system dysfunction of undetermined etiology (origin) should be screened for organic acids” (11). Their advice went largely unheeded, and in June 1996, Hoffmann et al. wrote: “We are convinced that this disorder frequently remains undiagnosed and misdiagnosed” (4). He reported an average delay in diagnosis of 15 months after the onset of the disease. One common misdiagnosis was post-encephalitic cerebral palsy.
Reporter Robert Kowalski learned that Glutaric Aciduria Type 1 was being misdiagnosed as child abuse and conducted an investigation. His findings were published in the October 6, 1996 edition of The Sunday Denver Post. The American Medical Association reprinted an excerpt of the article in a newsletter that went out to its 300,000 members. This led to heightened awareness and more screening. But sadly, many doctors remain unaware that an organic disease can cause the “hallmark” symptoms of Shaken Baby Syndrome.

What is Glutaric aciduria type 1 (GA-1)?

Glutaric Aciduria Type 1 is an inherited error of metabolism caused by one of at least 38 genetic mutations (12) with an “autosomal recessive mode of inheritance.” Nearly everyone has some defective recessive genes without knowing it. With GA-1, both parents carry a recessive gene that “matches up” and passes on to the child. Each child of such parents has a one in four chance of having the disorder. Glutaric aciduria is relatively common in some isolated populations such as the Amish of Pennsylvania and is more likely to show up when parents are related in some way. Köhler and Hoffmann report that the expected incidence in central Europe and the U.S. is about 1 in 30,000. Only about 100 confirmed cases exist in the U.S. at this time, but many doctors suspect the condition is frequently undiagnosed or misdiagnosed.

Metabolism is the sum total of the chemical processes by which food is changed into energy in our bodies. A child with glutaric aciduria is unable to metabolize (break down) certain proteins properly. The excess proteins create a toxic, acidic environment in the blood that can lead to irreversible neurological damage.

Children with glutaric aciduria often start life normally. They may seem healthy for several months and then progressively deteriorate, or an acute episode may be triggered by stress related to infection, surgery, or vaccinations (13, 14). Even a mild illness can lead to permanent brain injury, paralysis, or death. Fever, pain, and stress can increase the rate of metabolism. The onset of acute symptoms can follow skipped meals when a child is ill with a cold or the flu. The body then begins to metabolize (break down) muscle proteins for energy. This happens normally and accounts for the aches and pains of the flu. But patients with glutaric aciduria lack the enzyme (glutaryl-CoA dehydrogenase) that breaks down glutaric acid into water and carbon dioxide, an essential step in the process. Toxic levels of acid build up in the blood and body tissues. Seizures and brain damage can follow within a matter of hours.

Specifically, the liver in a person with GA-1 is unable to break down the amino acids lysine, hydroxylysine, and tryptophan (13).

What are the symptoms of GA-1?

Not everyone with the condition has the same symptoms. Some people do not have apparent symptoms and have not been diagnosed until adulthood (15). The following signs have been reported to occur in patients, but are not present in every case:

Macrocephaly (enlarged head)
Rapid head growth
Lack of head control
Developmental delay
Difficulty sitting
Deviation of gaze to the right
Movement disorder (unusual involuntary movements)
Dystonic posturing (unusual body postures)
Hypotonia (lethargy, sleepiness, “limpness”)
Spasticity or jerking movements
Profuse sweating

Medical tests such as a CT scan or MRI may reveal:

Frontotemporal cerebral atrophy (wasting away or shrinking of some of the brain)
Bitemporal arachnoid cysts
Widening of the Sylvian fissure
Delayed myelination
Basal ganglia atrophy
Subdural hematomas
Retinal hemorrhages in 20-30% of patients (3)

It has been proposed that in patients with cerebral atrophy, the shrinking of the brain’s hemispheres stretches the bridging veins across the enlarged subdural space (16). These stretched veins can bleed following a minor injury. Hoffmann wrote: “Chronic subdural effusions or hematomas (collections of blood) following relatively mild traumas occur frequently and may be mistaken as child abuse. Hematomas and subdural effusions in GDD (glutaryl-CoA dehydrogenase deficiency) probably result from minor traumas superimposed on preexisting widening of the subarachnoidal spaces. Subdural effusions and hematomas, even if associated with retinal hemorrhages, should therefore be considered as symptoms possibly associated with inborn errors of metabolism”(4).

How is Glutaric aciduria type 1 diagnosed?

Ideally, the disorder is diagnosed before acute symptoms appear because treatment can delay or prevent the most serious damage. Newborn screening by tandem mass spectrometry is available, but only a few states, including Pennsylvania, are now screening all newborns. There is a growing movement to include GA-1 among newborn screening tests because, although it is rare, its effects are devastating.

The first test is generally an organic acid analysis of urine. Glutaric acid is not normally present in urine, so a finding of it there makes the diagnosis likely. Sometimes, however, urine tests are normal because excretion is not constant (11,17,18). In such cases, increased concentrations of glutaric acid may be found in the cerebrospinal fluid.

The diagnosis is confirmed by measuring the activity of the enzyme glutaryl-CoA dehydrogenase in cultured skin fibroblasts or leukocytes. Fibroblasts are the large, flat, oval cells found in connective tissues and they are responsible for the formation of fibers. Leukocytes are white blood cells and are important in the body’s defense against infection.

A DNA test is also possible. The mutation occurs on the GCDH gene. If any of a deceased child¹s tissue is available, it can be determined whether he/she had the disorder.

How can GA-1 be treated?

There is no cure for GA-1. Children who are known to have the genetic condition are generally put on a low protein diet that restricts their intake of lysine and tryptophan. Oral riboflavin, L-carnitine, and tocopherol may also be given (13). In acute episodes, administration of sugar water intravenously can slow or stop the symptoms. The drug dextramethoraphan (present in some cough syrups) is thought to protect glutaric aciduria patients from brain injury when they are most vulnerable, during fevers and illnesses.

These treatments have been pioneered by Dr. Holmes Morton, an expert on inherited errors of metabolism. He received the Albert Schweitzer Prize for Humanitarianism in 1993 for his work with the Amish and Mennonite populations in Pennsylvania.


In conclusion, GA-1 should be screened out whenever Shaken Baby Syndrome is suspected, especially when there are no broken bones, and always when frontotemporal atrophy or widening of the Sylvian fissure is found. Hartley et al. wrote in 2001: “It has been suggested that multidisciplinary social assessment, expert ophthalmoscopy, radiographic skeletal survey supplemented by either a bone scan or repeat survey, coagulation screening, and neuroradiologic investigations should be mandatory in the investigations of infants with subdural hemorrhage. We propose that screening for GA-1 should be added to these investigations.” (3).

These links will lead you to other resources on GA-1:

International Organization of Glutaric Acidemia
RD #4, Box 299-A
Blairsville, PA 15717
Phone: 724-459-0179

Organic Acidemia Association
13210 35th Avenue North
Plymouth, MN 55441
Phone: 763-559-1797

Dr. Holmes Morton
P.O. Box 6086
Lancaster, PA 17607-6086
Phone: 717-872-7546

Allison’s Page, with links to resources for parents

Bibliographies in these articles will lead you to other articles.

1.Kowalski, Robert. Wrong diagnosis leads to child-abuse charges. The Sunday Denver Post, October 6, 1996, p. 28A.
Michael¹s whole story is told at:
2.Hartley LM, Mrcp B, Khwaja OS, Verity CM, Frcpch B. Glutaric aciduria type 1 and nonaccidental head injury. Pediatrics. 2001 Jan;107(1):174-5.
3.Hoffmann GF, Athanassopoulos S, Burlina AB, Duran M, de Klerk JB, Lehnert W, Leonard JV, Monavari AA, Muller E, Muntau AC, Naughten ER, Plecko-Starting B, Superti-Furga A, Zschocke J, Christensen E. Clinical course, early diagnosis, treatment, and prevention of disease in glutaryl-CoA dehydrogenase deficiency. Neuropediatrics. 1996 Jun;27(3):115-23.

4.Kafil-Hussain NA, Monavari A, Bowell R, Thornton P, Naughten E, O’Keefe M. Ocular findings in glutaric aciduria type 1. J Pediatr Ophthalmol Strabismus. 2000 Sep-Oct;37(5):289-93.

5.Köhler M, Hoffmann GF. Subdural haematoma in a child with glutaric aciduria type I. Pediatr Radiol. 1998 Aug;28(8):582.

6.Morris AA, Hoffmann GF, Naughten ER, Monavari AA, Collins JE, Leonard JV. Glutaric aciduria and suspected child abuse. Arch Dis Child. 1999 May;80(5):404-5.

7.Goodman SI, Markey SP, Moe PG, Miles BS, Teng CC. Glutaric aciduria; a “new” disorder of amino acid metabolism. Biochem Med. 1975 Jan;12(1):12-21.

8.Caffey J. The whiplash shaken infant syndrome: manual shaking by the extremities with whiplash-induced intracranial and intraocular bleedings, linked with residual permanent brain damage and mental retardation. Pediatrics. 1974 Oct;54(4):396-403.

9.Gregersen N, Brandt NJ, Christensen E, Gron I, Rasmussen K, Brandt S. Glutaric aciduria: clinical and laboratory findings in two brothers. J Pediatr. 1977 May;90(5):740-5.

10.Whelan DT, Hill R, Ryan ED, Spate M. L-Glutaric acidemia: investigation of a patient and his family. Pediatrics. 1979 Jan;63(1):88-93.

11.Zafeiriou DI, Zschocke J, Augoustidou-Savvopoulou P, Mauromatis I, Sewell A, Kontopoulos E, Katzos G, Hoffmann GF. Atypical and variable clinical presentation of glutaric aciduria type I. Neuropediatrics. 2000 Dec;31(6):303-6.

12.Stutchfield P, Edwards MA, Gray RG, Crawley P, Green A. Glutaric aciduria type I misdiagnosed as Leigh’s encephalopathy and cerebral palsy. Dev Med Child Neurol. 1985 Aug;27(4):514-8.

13.Alkan A, Baysal T, Yakinci C, Sigirci A, Kutlu R. Glutaric aciduria type I diagnosed after poliovirus immunization: magnetic resonance findings. Pediatr Neurol. 2002 May;26(5):405-7.

14.Amir N, Elpeleg ON, Shalev RS, Christensen E. Glutaric aciduria type I: enzymatic and neuroradiologic investigations of two kindreds. J Pediatr. 1989 Jun;114(6):983-9.

15.Woelfle J, Kreft B, Emons D, Haverkamp F. Subdural hemorrhage as an initial sign of glutaric aciduria type 1: a diagnostic pitfall. Pediatr Radiol. 1996 Nov;26(11):779-81.

16.Campistol J, Ribes A, Alvarez L, Christensen E, Millington DS. Glutaric aciduria type I: unusual biochemical presentation. J Pediatr. 1992 Jul;121(1):83-6.

17.Pineda M, Ribes A, Busquets C, Vilaseca MA, Aracil A, Christensen E. Glutaric aciduria type I with high residual glutaryl-CoA dehydrogenase activity. Dev Med Child Neurol. 1998 Dec;40(12):840-2