UMMS Affiliation

Department of Pediatrics

Publication Date

2020-11-01

Document Type

Article

Disciplines

Congenital, Hereditary, and Neonatal Diseases and Abnormalities | Nutritional and Metabolic Diseases | Pediatrics

Abstract

Glutaric acidemia type 1 (GA1) is a disorder of cerebral organic acid metabolism resulting from biallelic mutations of GCDH. Without treatment, GA1 causes striatal degeneration in > 80% of affected children before two years of age. We analyzed clinical, biochemical, and developmental outcomes for 168 genotypically diverse GA1 patients managed at a single center over 31 years, here separated into three treatment cohorts: children in Cohort I (n = 60; DOB 2006-2019) were identified by newborn screening (NBS) and treated prospectively using a standardized protocol that included a lysine-free, arginine-enriched metabolic formula, enteral l-carnitine (100 mg/kg*day), and emergency intravenous (IV) infusions of dextrose, saline, and l-carnitine during illnesses; children in Cohort II (n = 57; DOB 1989-2018) were identified by NBS and treated with natural protein restriction (1.0-1.3 g/kg*day) and emergency IV infusions; children in Cohort III (n = 51; DOB 1973-2016) did not receive NBS or special diet. The incidence of striatal degeneration in Cohorts I, II, and III was 7%, 47%, and 90%, respectively (p < .0001). No neurologic injuries occurred after 19 months of age. Among uninjured children followed prospectively from birth (Cohort I), measures of growth, nutritional sufficiency, motor development, and cognitive function were normal. Adherence to metabolic formula and l-carnitine supplementation in Cohort I declined to 12% and 32%, respectively, by age 7 years. Cessation of strict dietary therapy altered plasma amino acid and carnitine concentrations but resulted in no serious adverse outcomes. In conclusion, neonatal diagnosis of GA1 coupled to management with lysine-free, arginine-enriched metabolic formula and emergency IV infusions during the first two years of life is safe and effective, preventing more than 90% of striatal injuries while supporting normal growth and psychomotor development. The need for dietary interventions and emergency IV therapies beyond early childhood is uncertain.

Keywords

Arginine, Carnitine, Dystonia, Glutaric acidemia, Lysine, Medical food, Striatal degeneration

Rights and Permissions

© 2020 The Authors. This is an open access article under the CC BY license (http://creativecommons.org/licenses/BY/4.0/).

DOI of Published Version

10.1016/j.ymgme.2020.09.007

Source

Strauss KA, Williams KB, Carson VJ, Poskitt L, Bowser LE, Young M, Robinson DL, Hendrickson C, Beiler K, Taylor CM, Haas-Givler B, Hailey J, Chopko S, Puffenberger EG, Brigatti KW, Miller F, Morton DH. Glutaric acidemia type 1: Treatment and outcome of 168 patients over three decades. Mol Genet Metab. 2020 Nov;131(3):325-340. doi: 10.1016/j.ymgme.2020.09.007. Epub 2020 Oct 4. PMID: 33069577. Link to article on publisher's site

Journal/Book/Conference Title

Molecular genetics and metabolism

Comments

Full author list omitted for brevity. For the full list of authors, see article.

Related Resources

Link to Article in PubMed

PubMed ID

33069577

Creative Commons License

Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.

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