Children's Autism Metabolome Project

The purpose of this study is to identify a metabolite signature in blood plasma and/or urine
using a panel of biomarker metabolites that differentiate children with autism spectrum
disorder (ASD) from children with delayed development (DD) and/or typical development (TD),
to develop an algorithm that maximizes sensitivity and specificity of the biomarker profile,
and to evaluate the algorithm as a diagnostic tool.

A secondary objective is to define metabolites capable of classifying subtypes of ASD that
may increase understanding of the metabolic basis of the condition, as well as inform on
personalized therapy.

The population targeted for this study includes children aged 18 months to 48 months,
diagnosed with ASD or DD using behavioral criteria, and TD children, identified as having no
indications of ASD or DD using behavioral criteria. The target size for each of the three
groups is 500 children, for a total of 1500 subjects. The targeted male:female ratio is 4:1
in all three groups. If the diagnostic biomarkers identified in the study do not perform well
in females during the biomarker discovery phase, the study may be expanded to recruit more
females to examine the possibility of a female-specific diagnostic test.

Subjects will be qualified for entry into the study and will be invited to participate. On
the first study day, subjects' parents will sign an informed consent form and will be asked
questions on the mother's pregnancy and of both parents' medical history. A complete medical
history, a physical examination, and information needed to obtain a diagnosis of ASD, DD, or
TD will be obtained on the study subject. If possible, a urine sample will be collected
during the visit. Up to four tubes of blood (<25 mLs total) will be drawn at the clinic
during the visit or within 14 days following this initial visit. An overnight fast is
required prior to the visit where blood will be taken from the subject. A subset of the
subjects will be asked to return to the clinic 30-60 days later to obtain a replicate
metabolic profile.

The study will be divided into a biomarker discovery/method development phase followed by a
validation phase of the analytical methods and algorithm that will be used in the clinical
test.

The first 375 subjects enrolled in each group (ASD, DD, TD) will be used in the
discovery/training set and the remaining 125 subjects will be held aside for use as a
validation set. The training set will be used for discovery of the biomarkers and development
of the analytical methods intended for the diagnostic test. The validation sample set will be
used to evaluate performance of the final clinical methods and algorithms.

Consent will also be sought from all subjects for follow-up contact up to 2 years following
enrollment to determine the accuracy of the original behavioral diagnosis. Subjects chosen
for follow-up will be identified based on the strength of the diagnosis from the behavioral
scores and physician assessments as well as the biomarker profiles observed in individuals.

Inclusion Criteria:

- Age of greater or equal to 18 months and less than or equal to 48 months

- Fulfills the definition of an autism spectrum disorder, developmentally delayed, or
typically developing child in the age range 18-48 months, as determined by a clinician
or certified practitioner of the appropriate tests and who is knowledgeable in the
field; and

- Has parental (or other legal guardian ) informed consent to participate.

Exclusion Criteria:

- Diagnosis with a chronic condition that could interfere with a diagnosis of ASD or DD,
(e.g.: a known history of Fragile X, Rett syndrome, Down syndrome, tuberous sclerosis,
trisomy 21, inborn errors of metabolism or other genetic disorder that includes some
symptoms of autism)

- Fetal alcohol syndrome, or other serious neurological disorder

- Other serious metabolic disorder, psychiatric disorder, or medical condition involving
the liver, kidney, pulmonary, cardiovascular or endocrine systems

- A second child within a family in which a sibling has already been enrolled.

- A child who has previously participated in the CAMP-01 study