Glutaric Acidemia, Pathogenesis and Nutritional Therapy.

Qian Li,Yazi Zhao,Heinrich Körner,Hong Liu,Hongkang Men,Chunlan Yang,Yong Su,Lijuan Feng,Yan Huang,Xinming Wang

doi:10.3389/fnut.2021.704984

Abstract

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.

Highlights

Both types of Glutaric acidemia (GA) are autosomal recessive, metabolic disorders
Glutaric acidemia type II (GA-II) is an inherited deficiency of acyl-CoA dehydrogenases, such as short, medium, and long-chain acyl CoA dehydrogenases, which is caused by a defect in either electron transfer flavoprotein (ETF) or electron transfer flavoprotein dehydrogenase (ETFDH) [5]
Individuals should immediately start emergency treatment in hospital: [1] intravenous injections of Glucose, it may need to provide 12– 15 g/kg/24 h of glucose for 0–1 years, 10–12 and 8–10g/kg/24 h for 1–3 and 3–6 year of age, if persistent hyperglycemia >150– 180 mg/dL (>8–10 mmol/L) and/or glucosuria occurs, start insulin and adjust the infusion rate according to serum glucose; [2] Protein intake: Stop natural protein for up to 24 h, and reintroduce and increase stepwise until maintenance treatment is reached within 48–72 h, amino acid mixtures (AAM) should be administered according to maintenance therapy; [3] L- carnitine: 100 mg/kg/d via intravenous infusion

Summary

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]. This treatment is followed by maintenance therapy that combines low lysine diet with lysine-free, tryptophan-reduced amino acid supplements (AAS) and prevention of secondary carnitine depletion by carnitine supplementation.

Results

Conclusion