Sign Up for a Free Account
  • Updated 08.18.2022
  • Released 11.28.1994
  • Expires For CME 08.18.2025

Glutaric aciduria



Glutaric aciduria or acidemia type I is biochemically characterized by an accumulation of putatively neurotoxic glutaric and 3-hydroxyglutaric acid and nontoxic glutarylcarnitine. The majority of untreated individuals manifest dystonia due to striatal injury in infancy. Long-term observational studies, however, have demonstrated that one third of neonatally screened individuals still develop neurologic symptoms. Furthermore, progressive white matter abnormalities, subependymal nodules, malignant brain tumors, and chronic kidney disease have been reported in a subgroup of patients, raising concerns about the long-term disease outcome and highlighting the need for safer and more effective therapies. In this update, the author discusses the results of five studies demonstrating enlargement of the optic chiasm as a novel imaging finding. The studies showed that individuals with the high-excreter biochemical subtype have a higher risk of incidental subdural hematomas and cognitive dysfunction compared to those with the low-excreter subtype and confirmed the major impact of early diagnosis and therapeutic quality on the neurologic outcome of affected individuals.

Key points

• The precondition for preventing striatal injury is identifying patients during the newborn period when asymptomatic and starting metabolic treatment immediately.

• Intensified emergency treatment should be started without delay and before neurologic symptoms occur during each putatively threatening episode, such as infectious disease.

• Treatment should be initiated and patients should be followed by an interdisciplinary team of metabolic specialists, dieticians, psychologists, neurologists, physical therapists, and occupational therapists.

• In a neonatally screened population, quality of therapy becomes the major predictor of neurologic outcome and survival.

Historical note and terminology

Glutaric aciduria or acidemia type I (glutaryl-CoA dehydrogenase [GCDH] deficiency) was first described in 1975 (27) and is caused by inherited deficiency of GCDH (EC, an essential enzyme for the catabolism of lysine, hydroxylysine, and tryptophan (18; 21). The human GCDH gene was assigned to chromosome 19p13.13 (29).

First observational studies included patients from the Amish community (76; 75), Saulteaux/Ojibwa (Oji-Cree) First Nations (30), and European patients (37; 36; 16; 50). The first meta-analysis evaluated published case reports of the prescreening era describing 115 post-symptomatically treated patients (05). The second meta-analysis evaluated long-term observational studies of individuals identified by neonatal screening programs (N=261) in comparison to those diagnosed after the onset of symptoms (N=386) (10). An international cross-sectional study enrolling 279 patients investigated the impact of the diagnosis and mode of therapy on the neurologic outcome and survival (46). Development of tandem mass spectrometry-based programs for expanded neonatal screening has provided the opportunity to diagnose affected individuals before onset of irreversible striatal damage (53), and to start prospective follow-up studies (76; 77; 45; 06; 33; 11).

At present, more than 700 patients have been reported worldwide. A guideline for diagnosis and management has been introduced (42) and revised twice (43; 13), and the beneficial effect of using this guideline has been confirmed (33; 11; 10; 77).

The EIMD Patient Registry is an international registry for intoxication type metabolic diseases and includes follow-up data for over 250 patients (48).

A variety of studies have focused on the pathogenetic mechanisms involved in acute neurodegeneration of this disease using in vitro and in vivo models and have been reviewed by various authors (47; 38; 81). Gcdh-deficient mice, an animal model for this disease, have been developed and are still under investigation (40; 65; 64; 66; 85; 84; 20; 69).

This is an article preview.
Start a Free Account
to access the full version.

  • Nearly 3,000 illustrations, including video clips of neurologic disorders.

  • Every article is reviewed by our esteemed Editorial Board for accuracy and currency.

  • Full spectrum of neurology in 1,200 comprehensive articles.

  • Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660



ISSN: 2831-9125