Evidence for treatable inborn errors of metabolism in a cohort of 187 Greek patients with autism spectrum disorder (ASD).

[phenylketonuria]

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 (1 st 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 .

Diseases
Validation

Diseases presenting "elevated methylcitrate" symptom

phenylketonuria

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