TY - JOUR
T1 - Evidence for treatable inborn errors of metabolism cohort of 187 greek patients with autism spectrum (ASD)
AU - Spilioti, Martha
AU - Evangeliou, Athanasios E.
AU - Tramma, Despoina
AU - Theodoridou, Zoe
AU - Metaxas, Spyridon
AU - Michailidi, Eleni
AU - Bonti, Eleni
AU - Frysira, Helen
AU - Haidopoulou, A.
AU - Asprangathou, Despoina
AU - Tsalkidis, Aggelos J.
AU - Kardaras, Panagiotis
AU - Wevers, Ron A.
AU - Jakobs, Cornelis
AU - Michael Gibson, K.
PY - 2013/12/24
Y1 - 2013/12/24
N2 - We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4-14years 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.
AB - We screened for the presence of inborn errors of metabolism (IEM) in 187 children (105 males; 82 females, ages 4-14years 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.
KW - 3-hydroxyisovaleric acid
KW - Autism
KW - Biotin
KW - Inborn errors of metabolism
KW - Ketogenic diet
KW - Lesch-nyhan disease
KW - Phenylketonuria
KW - Succinic semialdehyde dehydrogenase deficiency
UR - http://www.scopus.com/inward/record.url?scp=84891649887&partnerID=8YFLogxK
U2 - 10.3389/fnhum.2013.00858
DO - 10.3389/fnhum.2013.00858
M3 - Article
AN - SCOPUS:84891649887
SN - 1662-5161
VL - 7
JO - Frontiers in Human Neuroscience
JF - Frontiers in Human Neuroscience
IS - DEC
M1 - 858
ER -