Autism Spectrum Disorder in a Child with Propionic Acidemia

Abstract

Autism is a neurodevelopmental disorder characterized by a combination of reciprocal social deficits, communication impairment, and rigid ritualistic interests. While autism does not have an identifying cause in most of the cases, it is associated with known medical conditions in at least 10% of cases. Although uncommon, cases of autism have also been reported in association with metabolic disorders. In this brief report, we describe the occurrence of autism in a 7-year-old girl with propionic acidemia (PA), a common form of organic aciduria resulting from the deficiency of propionyl-CoA carboxylase and characterized by frequent and potentially lethal episodes of metabolic acidosis often accompanied by hyperammonemia. It is particularly common in countries with high rates of consanguinity. Early diagnosis of autism in patients with metabolic disorders is important since autistic features are sometimes the most disruptive of all the child's problems. This facilitates providing the needed behavioral services not otherwise available for children with metabolic disorders.

Short-chain fatty acid fermentation products of the gut microbiome: implications in autism spectrum disorders

“…Furthermore, behaviors and gut symptoms improve following the elimination of these products from the diet (17, 106) or the eradication of PPA-producing bacteria by broad-spectrum antibiotics (109). Moreover, symptom exacerbation associated with propionic acidemia and its related conditions bears some resemblance to that reported in ASDs (86, 92, 93). Stool (67) and serum studies from patients with ASDs provide further evidence linking PPA to the condition, as patients with ASDs have metabolic dysfunction, including impairments in B12, glutathione, or carnitine metabolism (110, 111) and mitochondrial disorder/dysfunction (20), which are consistent with the effects of PPA on cellular metabolism (46, 51, 53).…”

“…For example, a number of inherited and acquired conditions, such as propionic/methylmalonic acidemia, biotinidase/holocarboxylase deficiency, ethanol/valproate exposure, and, as discussed, mitochondrial disorders, are all known to result from elevations of PPA and other SCFAs, partly through the formation of propionyl coenzyme A (CoA) and sequestration of carnitine (20, 46, 51, 91). Collectively, these conditions present at varying ages with developmental delay and regression, seizure/movement disorder, metabolic acidosis, and gastrointestinal symptoms, which also change in severity with fluctuating PPA levels and markers of mitochondrial dysfunction that are somewhat reminiscent of ASDs (86, 92, 93). …”

“…Interestingly, some other patients, including identical twins of more severely affected siblings, may present later in life with varying severities of the disorder, often without measurable increases in blood or urine PPA or metabolites. Treatment includes reduction of carbohydrate and protein contents in the diet, eradication of PPA-producing bacteria, and carnitine supplementation to improve PPA clearance, which have some benefit (46, 86, 92, 93). …”

Autism in patients with propionic acidemia

“…Furthermore, amino acid levels in autistic patients have been reported as significantly different from non-autistic control groups [3,5,14]. Inborn errors of metabolism such as propionic acidemia have been suggested to increase the risk for autism in a few cases [4,18]. Interestingly in another case report partial biotinidase deficiency, leading among others to decreased activity of propionyl-CoA carboxylase, the defective enzyme in PA, could also cause ASD [13].…”

Can psychiatric childhood disorders be due to inborn errors of metabolism?

“…Benvenuto [15] names PKU, adenylosuccinase deficit, SLOS, creatine deficiency syndromes and mitochondrial disorders as possible causes of syndromic autism. Case reports of autism in association with acute intermittent porphyria [16], propionic academia [17] and L-2-hydroxyglutaric aciduria [18] were found. Kaluzna-Czaplinska [19] focusses on the role of homocysteine in autism.…”