Glutaric Acidemia, Pathogenesis and Nutritional Therapy

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.

Exploring genotype–phenotype correlations in glutaric aciduria type 1

“…Still, there are many countries where GA1 is not included in NBS, or where NBS is not performed at all, and where the awareness of this rare disease is lacking, leading to very late diagnosis and a poorer treatment outcome. The differences of treatment strategies in the past, but also a general missed continuity of treatment make the patient comparability difficult 157,158 . An appropriate treatment strategy, continuity and emergency strategy are necessary to improve the patients' outcome 159,160 .…”

Case report: Novel ETFDH compound heterozygous mutations identified in a patient with late-onset glutaric aciduria type II

“…In addition to riboflavin treatment, a low-fat, low-protein, and high-carbohydrate diet should be provided to reduce metabolic disorders and ensure an adequate energy supply. L-carnitine and coenzyme Q10 can also be given to patients with carnitine deficiency and coenzyme Q10 deficiency, respectively (31). Since the high clinical heterogeneity and treatability of late-onset GA II, screening the hot spot mutations in Chinese patients clinically suspected of GA II could be beneficial for its early diagnosis and treatment, during which the WES strategy would be a great tool to identify novel pathogenic spots.…”

Seguimiento bioquímico y dosis de medicamentos de EIM del metabolismo intermedio

“…En la enfermedad de orina con olor a jarabe de maple (arce), causada por una deficiencia en la actividad del complejo de la deshidrogenasa de los alfa cetoácidos de cadena ramificada, cuyo cofactor es la tiamina tampoco, se ha documentado que exista una respuesta favorable con la suplementación en mega dosis. 9,10,11 Cuadro 1 [12][13][14][15][16][17][18][19][20] La terapia de remplazo enzimático se administra de forma intravenosa con enzimas recombinantes y ha sido exitosa en enfermedades de depósito lisosomal tales como la enfermedad de Gaucher y Fabry. Actualmente, algunas enzimas bacterianas modificadas tales como el pegvaliase se están empezando a utilizar por vía subcutánea, como la nueva terapia de sustitución enzimática para pacientes con fenilcetonuria.…”

“…Errores innatos del metabolismo intermedio que responden a megadosis de coenzimas. [12][13][14][15][16][17][18][19][20]…”