Glutaric Acidemia, Pathogenesis and Nutritional Therapy

• 19 December 2024

Glutaric Acidemia, Pathogenesis and
Nutritional Therapy
Qian Li 1, Chunlan Yang2, Lijuan Feng2, Yazi Zhao2, Yong Su2, Hong Liu2, Hongkang Men3,
Yan Huang2*, Heinrich Körner 4* and Xinming Wang2,4*
1 Department of Pharmacy, Suizhou Hospital, Hubei University of Medicine, Suizhou, China, 2 Department of Pharmacy, First
Affiliated Hospital of Anhui Medical University, Hefei, China, 3 School of Pharmacy, Anhui Medical University, Hefei, China,
4 Key Laboratory of Anti-inflammatory and Immune Medicine, Anhui Collaborative Innovation Center of Anti-inflammatory and
Immune Medicine, Institute of Clinical Pharmacology, Ministry of Education, Anhui Medical University, Hefei, China
Glutaric acidemia (GA) are heterogeneous, genetic diseases that present with specific
catabolic deficiencies of amino acid or fatty acid metabolism. The disorders can be
divided into type I and type II by the occurrence of different types of recessive mutations
of autosomal, metabolically important genes. Patients of glutaric acidemia type I (GA-I)
if not diagnosed very early in infanthood, experience irreversible neurological injury
during an encephalopathic crisis in childhood. If diagnosed early the disorder can be
treated successfully with a combined metabolic treatment course that includes early
catabolic emergency treatment and long-term maintenance nutrition therapy. Glutaric
acidemia type II (GA- II) patients can present clinically with hepatomegaly, non-ketotic
hypoglycemia, metabolic acidosis, hypotonia, and in neonatal onset cardiomyopathy.
Furthermore, it features adult-onset muscle-related symptoms, including weakness,
fatigue, and myalgia. An early diagnosis is crucial, as both types can be managed
by simple nutraceutical supplementation. This review discusses the pathogenesis of
GA and its nutritional management practices, and aims to promote understanding and
management of GA. We will provide a detailed summary of current clinical management
strategies of the glutaric academia disorders and highlight issues of nutrition therapy
principles in emergency settings and outline some specific cases.
Keywords: Glutaric acidemia, pathogenesis, genetic disorders, maintenance therapy, nutrition therapy
INTRODUCTION
Both types of Glutaric acidemia (GA) are autosomal recessive, metabolic disorders. Glutaric
acidemia type I (GA-I) is a katabolic deficiency of the L-lysine, L-hydroxylysine and L-tryptophan
metabolism that was first described in 1975 (1). Its worldwide incidence is ∼1 in 110,000, which
makes it one of the more common inherited metabolic disorders that in total affect one out of
30,000–100,000 children (2). GA- I results primarily, in the accumulation of glutaric acid (GA)
and 3-hydroxyglutaric acid (3-OH-GA) in the urine, and secondarily, in carnitine deficiency (3).

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