Autism in patients with propionic acidemia.
Certain inborn errors of metabolism have been suggested to increase the risk of autistic behavior. In an animal model, propionic acid ingestion triggered abnormal behavior resembling autism. So far only a few cases were reported with propionic acidemia and autistic features. From a series of twelve consecutively diagnosed cases with propionic acidemia, we report on eight patients with autistic features. The patients were followed 2-4 times a year and underwent regular clinical, dietary and laboratory investigations. Psychological evaluation was performed every second to fourth year. All patients were compliant with the standard diet and carnitine supplementation. None of the patients had frequent metabolic decompensations. From the metabolic factors known to impact neuropsychological outcome we detected chronically decreased valine levels and altered valine to leucine ratios in five out of the eight patients. Recurrent lactic acid elevations were present in six out of the eight patients. Five of the eight patients were diagnosed with Autism Spectrum Disorder, four of them had pathogenic variants in PCCB. Disorder according to DSM-IV and/or DSM-5 criteria. One of the patients diagnosed with propionic acidemia by newborn screening had the most significant behavioral features and another was diagnosed with Autism Spectrum Disorder prior to propionic acidemia. We hypothesize that chronic suboptimal intracellular metabolic balance may be responsible for the increased risk for autistic features in propionic acidemia. We propose that patients diagnosed with propionic acidemia should be screened for Autism Spectrum Disorder.
Department of Pediatrics, Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
Peter
P
Witters
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA, USA.
Eric
E
Debbold
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA, USA.
Kea
K
Crivelly
Department of Pediatrics, Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
Kristel
K
Vande Kerckhove
Department of Pediatrics, Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
Karen
K
Corthouts
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA, USA.
Brett
B
Debbold
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA, USA.
Hans
H
Andersson
Department of Psychology, Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
Lena
L
Vannieuwenborg
Department of Psychology, Metabolic Center, University Hospitals Leuven, Leuven, Belgium.
Sam
S
Geuens
Division of Metabolism, Children's Research Center, University Children's Hospital Zurich, Zurich, Switzerland.
Matthias
M
Baumgartner
Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA, USA; Donders Institute for Brain, Neuroscience, Radboudumc, Nijmegen, The Netherlands.
Tamas
T
Kozicz
Department of Psychiatry, Tulane University School of Medicine, New Orleans, LA, USA.
Lisa
L
Settles
Department of Pediatrics, Metabolic Center, University Hospitals Leuven, Leuven, Belgium; Hayward Genetics Center, Tulane University School of Medicine, New Orleans, LA, USA. Electronic address: emoravakozicz@tulane.edu.
Eva
E
Morava
D000293:Adolescent; D000328:Adult; D000818:Animals; D000067877:Autism Spectrum Disorder / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D002648:Child; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007930:Leucine / Q000378:metabolism; D008297:Male; D043586:Methylmalonyl-CoA Decarboxylase / Q000235:genetics*; D015997:Neonatal Screening; D011422:Propionates / Q000378:metabolism; D056693:Propionic Acidemia / Q000150:complications / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D055815:Young Adult
D011422:Propionates; D043586:Methylmalonyl-CoA Decarboxylase; D007930:Leucine; C029658:propionic acid
ASD; Autistic; Dietary therapy; Intellectual disability; Lactic acid; Leucine; Mitochondria; Propionic acid; Valine