High levels of ketone bodies (acetoacetic acid, beta-hydroxybutyric acid, and acetone) in the urine. Ketone bodies are insignificant in the blood and urine of normal individuals in the postprandial or overnight-fasted state.

Excretion of non-amino organic acids in urine.

The imino acids, proline and hydroxyproline, share a renal tubular reabsorptive mechanism with glycine. Iminoglycinuria (IG; 242600), a benign inborn error of amino acid transport, is also a normal finding in neonates and infants under 6 months of age (Chesney, 2001). Early studies of families with iminoglycinuria suggested genetic complexity, with homozygotes developing IG and heterozygotes manifesting only hyperglycinuria (HG) (summary by Broer et al., 2008). A phenotype of combined glucosuria and glycinuria has been described (see 138070).

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

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

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

Cerebral palsy describes a group of permanent disorders of the development of movement and posture, causing activity limitation, that are attributed to nonprogressive disturbances that occurred in the developing fetal or infant brain. The motor disorders of cerebral palsy are often accompanied by disturbances of sensation, perception, cognition, communication, and behavior, by epilepsy, and by secondary musculoskeletal problems.

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.

Hyperreflexia is the presence of hyperactive stretch reflexes of the muscles.

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.

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.

Hypotonia is an abnormally low muscle tone (the amount of tension or resistance to movement in a muscle). Even when relaxed, muscles have a continuous and passive partial contraction which provides some resistance to passive stretching. Hypotonia thus manifests as diminished resistance to passive stretching. Hypotonia is not the same as muscle weakness, although the two conditions can co-exist.

The presence of skeletal muscular atrophy (which is also known as amyotrophy).

Generalized muscular hypotonia (abnormally low muscle tone).

Seborrheic dermatitis is a form of eczema which is closely related to dandruff. It causes dry or greasy peeling of the scalp, eyebrows, and face, and sometimes trunk.

A decreased concentration of glucose in the blood.

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.

Acidosis resulting from accumulation of ketone bodies.

An increased concentration of leucine in the blood.

Concentration of carnitine in the blood circulation below the lower limit of normal.

An increased concentration of ammonia in the blood with sudden onset.

Propionic acidemia is an autosomal recessive metabolic disorder caused by defective functioning in the mitochondrial enzyme propionyl CoA carboxylase (PCC), resulting in the accumulation of propionic acid metabolites, and dysfunction in the respiratory chain and urea cycle pathways. The disorder is clinically heterogeneous. A neonatal-onset form is characterized by poor feeding, vomiting, and fatigue in the first days of life in a previously healthy infant, and if untreated, may be followed by lethargy, seizures, coma, and death. The neonatal form is frequently accompanied by metabolic acidosis with anion gap, ketonuria, hypoglycemia, hyperammonemia, and cytopenia. A late-onset form in older children and adults has a milder phenotype, is less common, and may present with developmental regression, chronic vomiting, protein intolerance, failure to thrive, hypotonia, and occasionally basal ganglia infarction, which may result in dystonia and choreoathetosis, and cardiomyopathy. Metabolically unstable individuals can have an acute decompensation that resembles the neonatal presentation, often precipitated by a catabolic stress such as infection, injury, or surgery, or an excessive intake of intact (i.e., complete, dietary, or natural) protein. Long-term manifestations of neonatal and late onset of propionic acidemia can include growth impairment, intellectual disability, seizures, basal ganglia lesions, pancreatitis, and cardiomyopathy. Other less common manifestations include optic atrophy, hearing loss, premature ovarian insufficiency, and chronic renal failure (summary by Jurecki et al., 2019).

An increased concentration of ammonia in the blood.

A noncongenital process of hair loss, which may progress to partial or complete baldness.