An increased concentration of an amino acid in the urine.

Orotic aciduria is a rare autosomal recessive disorder characterized by megaloblastic anemia and orotic acid crystalluria that is frequently associated with some degree of physical and mental retardation. These features respond to appropriate pyrimidine replacement therapy, and most cases appear to have a good prognosis. A minority of cases have additional features, particularly congenital malformations and immune deficiencies, which may adversely affect this prognosis (summary by Webster et al., 2001). Bailey (2009) stated that only 2 cases of orotic aciduria without megaloblastic anemia (OAWA) had been reported.

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

Abnormally increased size of the liver.

Forceful ejection of the contents of the stomach through the mouth by means of a series of involuntary spasmic contractions.

The presence of excessive fibrous connective tissue in the liver. Fibrosis is a reparative or reactive process.

Impaired feeding performance of an infant as manifested by difficulties such as weak and ineffective sucking, brief bursts of sucking, and falling asleep during sucking. There may be difficulties with chewing or maintaining attention.

Abnormal accumulation of fluid in the brain.

Cerebellar ataxia refers to ataxia due to dysfunction of the cerebellum. This causes a variety of elementary neurological deficits including asynergy (lack of coordination between muscles, limbs and joints), dysmetria (lack of ability to judge distances that can lead to under- or overshoot in grasping movements), and dysdiadochokinesia (inability to perform rapid movements requiring antagonizing muscle groups to be switched on and off repeatedly).

The complete absence of wakefulness and consciousness, which is evident through a lack of response to any form of external stimuli.

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.

A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.

A proneness to anger, i.e., a tendency to become easily bothered or annoyed.

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.

Concentration of argininosuccinic acid in the cerebrospinal fluid (CSF) above the upper limit of normal.

Alkalosis due to excess loss of carbon dioxide from the body.

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

An increased concentration of glutamine in the blood.

A decreased concentration of arginine in the blood.

An increased level of the non-proteinogenic amino acid argininosuccinic acid in the blood circulation.

An increased concentration of ammonia in the blood.

Trichorrhexis nodosa is the formation of nodes along the hair shaft through which breakage readily occurs. It is thus a focal defect in the hair fiber that is characterized by thickening or weak points (nodes) that cause the hair to break off easily. The result is defective, abnormally fragile hair.

Fragile, easily breakable hair, i.e., with reduced tensile strength.

Hair that lacks the luster (shine or gleam) of normal hair.

Citrin deficiency can manifest in newborns or infants as neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD), in older children as failure to thrive and dyslipidemia caused by citrin deficiency (FTTDCD), and in adults as recurrent hyperammonemia with neuropsychiatric symptoms in citrullinemia type II (CTLN2). Often citrin deficiency is characterized by strong preference for protein-rich and/or lipid-rich foods and aversion to carbohydrate-rich foods. NICCD. Children younger than age one year have a history of low birth weight with growth restriction and transient intrahepatic cholestasis, hepatomegaly, diffuse fatty liver, and parenchymal cellular infiltration associated with hepatic fibrosis, variable liver dysfunction, hypoproteinemia, decreased coagulation factors, hemolytic anemia, and/or hypoglycemia. NICCD is generally not severe and symptoms often resolve by age one year with appropriate treatment, although liver transplantation has been required in rare instances. FTTDCD. Beyond age one year, many children with citrin deficiency develop a protein-rich and/or lipid-rich food preference and aversion to carbohydrate-rich foods. Clinical abnormalities may include growth restriction, hypoglycemia, pancreatitis, severe fatigue, anorexia, and impaired quality of life. Laboratory changes are dyslipidemia, increased lactate-to-pyruvate ratio, higher levels of urinary oxidative stress markers, and considerable deviation in tricarboxylic acid (TCA) cycle metabolites. One or more decades later, some individuals with NICCD or FTTDCD develop CTLN2. CTLN2. Presentation is sudden and usually between ages 20 and 50 years. Manifestations are recurrent hyperammonemia with neuropsychiatric symptoms including nocturnal delirium, aggression, irritability, hyperactivity, delusions, disorientation, restlessness, drowsiness, loss of memory, flapping tremor, convulsive seizures, and coma. Symptoms are often provoked by alcohol and sugar intake, medication, and/or surgery. Affected individuals may or may not have a prior history of NICCD or FTTDCD.