Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD).
Τίτλος | Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD). |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Spilioti, M., Evangeliou A. E., Tramma D., Theodoridou Z., Metaxas S., Michailidi E., Bonti E., Frysira H., Haidopoulou A., Asprangathou D., Tsalkidis A. J., Kardaras P., Wevers R. A., Jakobs C., & K Gibson M. |
Journal | Front Hum Neurosci |
Volume | 7 |
Pagination | 858 |
Date Published | 2013 |
ISSN | 1662-5161 |
Abstract | We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4-14 years old) who presented with confirmed features of autism spectrum disorder (ASD). Twelve patients (7%) manifested increased 3-hydroxyisovaleric acid (3-OH-IVA) excretion in urine, and minor to significant improvement in autistic features was observed in seven patients following supplementation with biotin. Five diagnoses included: Lesch Nyhan syndrome (2), succinic semialdehyde dehydrogenase (SSADH) deficiency (2), and phenylketonuria (1) (2.7%). Additional metabolic disturbances suggestive of IEMs included two patients whose increased urine 3-OH-IVA was accompanied by elevated methylcitrate and lactate in sera, and 30 patients that showed abnormal glucose-loading tests. In the latter group, 16/30 patients manifested increased sera beta hydroxybutyrate (b-OH-b) production and 18/30 had a paradoxical increase of sera lactate. Six patients with elevated b-OH-b in sera showed improved autistic features following implementation of a ketogenic diet (KD). Five patients showed decreased serum ketone body production with glucose loading. Twelve of 187 patients demonstrated non-specific MRI pathology, while 25/187 had abnormal electroencephalogram (EEG) findings. Finally, family history was positive for 22/187 patients (1st or 2nd degree relative with comparable symptomatology) and consanguinity was documented for 12/187 patients. Our data provide evidence for a new biomarker (3-OH-IVA) and novel treatment approaches in ASD patients. Concise 1 sentence take-home message: Detailed metabolic screening in a Greek cohort of ASD patients revealed biomarkers (urine 3-hydroxyisovaleric acid and serum b-OH-b) in 7% (13/187) of patients for whom biotin supplementation or institution of a KD resulted in mild to significant clinical improvement in autistic features. |
DOI | 10.3389/fnhum.2013.00858 |
Alternate Journal | Front Hum Neurosci |
PubMed ID | 24399946 |
PubMed Central ID | PMC3871708 |