Simplified Approach to Glutaric Acidurias: A Mini-Review

Abstract

Inherited metabolic diseases (IMDs), comprise a large class of genetic diseases affecting the metabolism. Expanded newborn screening from dried dried blood spot (DBS) samples for inborn errors of metabolism has increased the detection of metabolic disorders in asymptomatic newborns and reduced the morbidity and mortality by early interventions. Organic acidurias (OADs) arise from the defects in the intermediary metabolic pathways of carbohydrate, amino acid and fatty acid oxidation, leading to the accumulation of organic acids in tissues and their subsequent excretion in urine. Glutaric acidurias are a group of OADs which have three major types with different genetic mutations affecting different metabolic enzymes. In this mini-review we will compare three types of GA and their genotypes, symptoms, diagnosis, and treatments will be discussed briefly.

A novel mutation in the glutaryl‐CoA dehydrogenase gene (GCDH) in an Iranian patient affected with Glutaric acidemia type 1

“…The third category comes with a late start. 1 The child has symptoms like kidney cysts, hypospadias, cardiomyopathies, metabolic acidosis, sweaty feet odor, hypoglycemia without ketosis, and Rocker Bottom feet. The distinction between type 1 and 2 is that in type 2, the deficiency of Acetyl dehydrogenase does not only result in high secretion glutaric acid, but also increases the secretion of lactic acid, malonic acetate, butyric, isobutritic, 2-methylbutyric and Isovalic.…”

“…The second group the neonatal form without congenital anomalies. The third category comes with a late start 1 . The child has symptoms like kidney cysts, hypospadias, cardiomyopathies, metabolic acidosis, sweaty feet odor, hypoglycemia without ketosis, and Rocker Bottom feet.…”

“…It is an autosomal recessive disorder, and its diagnosis is made after the exclusion of the other types of the disease. It is caused by mutations in the succinylCoA:glutarate‐CoA transferase gene, which causes deficiency of succinate‐hydroxymethylglutarate CoA transferase, and thus a decreased conversion of free glutaric acid to glutaryl‐CoA, without clinical consequences 1 . Several common mutations have been identified so far including A421V in the Amish population in Pennsylvania, 14 IVS 1 + 5G> T in Canadian Indians Oji‐Cree, 15 E365K in Irish, 16 R402W in European population, 16,17 and IVS10‐2A> C in China 18 and Taiwan 19 .…”

“…Continuation of this process leads to the accumulation of organic acids in the tissues and eventually its excretion through the urine. 1 So far, more than 100 different types of organic acids have been found in urine, such as propionic aciduria (PA), methylmalonic aciduria (MMA), branched chain organic aciduria, glutaric acidurias (GAs), and multiple carboxylase deficiencies. 2,3 Glutaric acidurias are a branch of the OADs group that includes three different types caused by different genetic mutations.…”

“…One of the most important class of this classification are organic acidurias (OADs), which are caused by defects in intermediary metabolic pathways of carbohydrate, amino acid, and fatty acid oxidation. Continuation of this process leads to the accumulation of organic acids in the tissues and eventually its excretion through the urine 1 . So far, more than 100 different types of organic acids have been found in urine, such as propionic aciduria (PA), methylmalonic aciduria (MMA), branched chain organic aciduria, glutaric acidurias (GAs), and multiple carboxylase deficiencies 2,3 .…”