Diagnostic Criteria

Guidelines for diagnosis and management of glutaric acidemia type 1 (GA-1) due to deficiency or absence of functional glutaryl-CoA dehydrogenase were developed in 2007 and recently revised .

Suggestive Findings

Scenario 1: Positive Newborn Screening (NBS)

GA-1 should be suspected in infants with a positive NBS result. NBS for GA-1 primarily relies on measuring glutarylcarnitine (C5DC) in dried blood spots, which has been shown to have 96% sensitivity . Positive C5DC values (i.e., those above the cutoff reported by the screening laboratory) require follow-up biochemical testing with either urine organic analysis or quantitative glutaric and 3-hydroxyglutaric acid, with preference for quantitative studies if available.

Source: GeneReviews — "Glutaric Acidemia Type 1"

Differential Diagnosis

Table 2. Other Genes of Interest in the Differential Diagnosis of Glutaric Acidemia Type 1 (GA-1)

Management Guidelines

When glutaric acidemia type 1 (GA-1) is suspected during the diagnostic evaluation (i.e., due to elevated concentration of 3-OH-GA in plasma or urine), metabolic treatment should be initiated immediately. Development and evaluation of treatment plans, training and education of affected individuals and their families, and avoidance of side effects of dietary treatment (i.e., malnutrition, growth failure) require a multidisciplinary approach to care including multiple subspecialists, with oversight and expertise from a specialized metabolic center. The second revision of consensus clinical practice guidelines for the treatment of individuals with GA-1 have recently been published .

Evaluations Following Initial Diagnosis

To establish the extent of disease and needs in an individual following diagnosis of GA-1, the evaluations summarized (if not performed as part of the evaluation that led to diagnosis) are recommended.

Table 3.

Recommended Evaluations Following Initial Diagnosis of GA-1

Evaluation | Comment

Consultation w/metabolic physician / biochemical geneticist specialist metabolic dietician1 | • Transfer to specialist center w/experience in management of inherited metabolic diseases is strongly recommended.

• Consider short hospitalization at center of expertise for inherited metabolic conditions to provide detailed education (natural history, maintenance emergency treatment, prognosis, risks for acute encephalopathic crises) for caregivers.

Source: GeneReviews — "Glutaric Acidemia Type 1"

Clinical Guidance

Avoid the following:

• Excessive dietary protein or protein malnutrition inducing catabolic state

• Prolonged fasting

• Catabolic illness (intercurrent infection; brief febrile illness post-vaccination)

• Inadequate caloric provision during other stressors, especially when fasting is involved (surgery or procedure requiring fasting/anesthesia)

Although there are no data on which to base such a recommendation, given the increased risk of subdural hemorrhage in individuals with GA-1, avoidance or extreme caution with contact sports and physical activities that involve high risk for minor head injuries would appear to be a sensible precaution.

Source: GeneReviews — "Glutaric Acidemia Type 1"

Surveillance Guidelines

Regular evaluations by a metabolic specialist and metabolic dietician are appropriate. See for additional recommended surveillance. Table 9. Recommended Surveillance for Individuals with Glutaric Aciduria Type 1

Source: GeneReviews — "Glutaric Acidemia Type 1"