TY - JOUR
TI - Evidence for treatable inborn errors of metabolism in a cohort of 187
Greek patients with autism spectrum disorder (ASD)
AU - Spilioti, Martha
AU - Evangeliou, Athanasios E.
AU - Tramma, Despoina and
AU - Theodoridou, Zoe
AU - Metaxas, Spyridon
AU - Michailidi, Eleni
AU - Bonti,
AU - Eleni
AU - Frysira, Helen
AU - Haidopoulou, A.
AU - Asprangathou, Despoina
AU - and Tsalkidis, Aggelos J.
AU - Kardaras, Panagiotis
AU - Wevers, Ron A.
AU - and Jakobs, Cornelis
AU - Gibson, K. Michael
JO - Frontiers in Human Neuroscience
PY - 2013
VL - 7
TODO - null
SP - null
PB - Frontiers Research Foundation
SN - null
TODO - 10.3389/fnhum.2013.00858
TODO - autism; inborn errors of metabolism; biotin; ketogenic diet;
3-hydroxyisovaleric acid; Lesch-Nyhan disease; succinic semialdehyde
dehydrogenase deficiency; phenylketonuria
TODO - 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.
ER -