Increased concentration of uracil in the urine.

The amount of dihydrouracil in the urine, normalized for urine concentration, is above the upper limit of normal.

The amount of dihydrothymine in the urine, normalized for urine concentration, is above the upper limit of normal.

The amount of thymine in the urine, normalized for urine concentration, is above the upper limit of normal.

Clubfoot is a congenital limb deformity defined as fixation of the foot in cavus, adductus, varus, and equinus (i.e., inclined inwards, axially rotated outwards, and pointing downwards) with concomitant soft tissue abnormalities (Cardy et al., 2007). Clubfoot may occur in isolation or as part of a syndrome (e.g., diastrophic dysplasia, 222600). Clubfoot has been reported with deficiency of long bones and mirror-image polydactyly (Gurnett et al., 2008; Klopocki et al., 2012).

Short (hypoplastic) phalanx of finger, affecting one or more phalanges.

A deficiency or slowing down of growth pre- and postnatally.

Failure to thrive (FTT) refers to a child whose physical growth is substantially below the norm.

Congenital absence of the anus, i.e., the opening at the bottom end of the intestinal tract.

Impaired ability to eat related to problems gathering food and getting ready to suck, chew, or swallow it.

Autism, the prototypic pervasive developmental disorder (PDD), is usually apparent by 3 years of age. It is characterized by a triad of limited or absent verbal communication, a lack of reciprocal social interaction or responsiveness, and restricted, stereotypic, and ritualized patterns of interests and behavior (Bailey et al., 1996; Risch et al., 1999). 'Autism spectrum disorder,' sometimes referred to as ASD, is a broader phenotype encompassing the less severe disorders Asperger syndrome (see ASPG1; 608638) and pervasive developmental disorder, not otherwise specified (PDD-NOS). 'Broad autism phenotype' includes individuals with some symptoms of autism, but who do not meet the full criteria for autism or other disorders. Mental retardation coexists in approximately two-thirds of individuals with ASD, except for Asperger syndrome, in which mental retardation is conspicuously absent (Jones et al., 2008). Genetic studies in autism often include family members with these less stringent diagnoses (Schellenberg et al., 2006). Levy et al. (2009) provided a general review of autism and autism spectrum disorder, including epidemiology, characteristics of the disorder, diagnosis, neurobiologic hypotheses for the etiology, genetics, and treatment options. Genetic Heterogeneity of Autism Autism is considered to be a complex multifactorial disorder involving many genes. Accordingly, several loci have been identified, some or all of which may contribute to the phenotype. Included in this entry is AUTS1, which has been mapped to chromosome 7q22. Other susceptibility loci include AUTS3 (608049), which maps to chromosome 13q14; AUTS4 (608636), which maps to chromosome 15q11; AUTS6 (609378), which maps to chromosome 17q11; AUTS7 (610676), which maps to chromosome 17q21; AUTS8 (607373), which maps to chromosome 3q25-q27; AUTS9 (611015), which maps to chromosome 7q31; AUTS10 (611016), which maps to chromosome 7q36; AUTS11 (610836), which maps to chromosome 1q41; AUTS12 (610838), which maps to chromosome 21p13-q11; AUTS13 (610908), which maps to chromosome 12q14; AUTS14A (611913), which has been found in patients with a deletion of a region of 16p11.2; AUTS14B (614671), which has been found in patients with a duplication of a region of 16p11.2; AUTS15 (612100), associated with mutation in the CNTNAP2 gene (604569) on chromosome 7q35-q36; AUTS16 (613410), associated with mutation in the SLC9A9 gene (608396) on chromosome 3q24; AUTS17 (613436), associated with mutation in the SHANK2 gene (603290) on chromosome 11q13; AUTS18 (615032), associated with mutation in the CHD8 gene (610528) on chromosome 14q11; AUTS19 (615091), associated with mutation in the EIF4E gene (133440) on chromosome 4q23; and AUTS20 (618830), associated with mutation in the NLGN1 gene (600568) on chromosome 3q26. (NOTE: the symbol 'AUTS2' has been used to refer to a gene on chromosome 7q11 (KIAA0442; 607270) and therefore is not used as a part of this autism locus series.) There are several X-linked forms of autism susceptibility: AUTSX1 (300425), associated with mutations in the NLGN3 gene (300336); AUTSX2 (300495), associated with mutations in NLGN4 (300427); AUTSX3 (300496), associated with mutations in MECP2 (300005); AUTSX4 (300830), associated with variation in the region on chromosome Xp22.11 containing the PTCHD1 gene (300828); AUTSX5 (300847), associated with mutations in the RPL10 gene (312173); and AUTSX6 (300872), associated with mutation in the TMLHE gene (300777). A locus on chromosome 2q (606053) associated with a phenotype including intellectual disability and speech deficits was formerly designated AUTS5. Folstein and Rosen-Sheidley (2001) reviewed the genetics of autism.

A state of disinterest, listlessness, and indifference, resulting in difficulty performing simple tasks or concentrating.

A seizure is an intermittent abnormality of nervous system physiology characterized by a transient occurrence of signs and/or symptoms due to abnormal excessive or synchronous neuronal activity in the brain.

Functional neurological abnormalities related to dysfunction of the pyramidal tract.

Hyperactivity is a condition characterized by constant and unusually high levels of activity, even in situations where it is deemed inappropriate.

A degree of language development that is significantly below the norm for a child of a specified age.

An abnormality of the cerebral white matter.

Intellectual disability, previously referred to as mental retardation, is characterized by subnormal intellectual functioning that occurs during the developmental period. It is defined by an IQ score below 70.

Any structural abnormality of the pyramidal tract, whose chief element, the corticospinal tract, is the only direct connection between the brain and the spinal cord. In addition to the corticospinal tract, the pyramidal system includes the corticobulbar, corticomesencephalic, and corticopontine tracts.

A state of abnormally strong desire for sleep during the daytime.

The concentration of dihydrouracil in the cerebrospinal fluid (CSF) is above the upper limit of normal.

Sudden and involuntary contractions of one or more muscles brought on by physical exertion.

Asymmetric head shape, which is usually a combination of unilateral occipital flattening with ipsilateral frontal prominence, leading to rhomboid cranial shape.

Head circumference below 2 standard deviations below the mean for age and gender.

The concentration of aspartate aminotransferase (AST) in the blood circulation is above the upper limit of normal.

An abnormally high concentration in the circulation of alanine aminotransferase (ALT).

Metabolic acidosis (MA) is characterized by a fall in blood pH due to a reduction of serum bicarbonate concentration. This can occur as a result of either the accumulation of acids (high anion gap MA) or the loss of bicarbonate from the gastrointestinal tract or the kidney (hyperchloremic MA). By definition, MA is not due to a respirary cause.

An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

Concentration of fructose 1,6-bisphosphate aldolase in the blood circulation above the upper limit of normal.

An abnormal reduction in dihydropyrimidine dehydrogenase (NADP+) level.

Concentration of uracil in the blood circulation is above the normal range.

An increased concentration of dihydrouracil in the blood circulation. Dihydrouracil is an intermediate in the catabolism of uracil that is also known as 5,6-dihydrouracil.

Concentration of the nucleobase thymine in the blood circulation above the normal range.

Activity of dihydropyrimidinase in the liver below the lower limit of normal.