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

An abnormally increased muscular tone that causes fixed abnormal postures. There is a slow, intermittent twisting motion that leads to exaggerated turning and posture of the extremities and trunk.

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.

Encephalopathy is a term that means brain disease, damage, or malfunction. In general, encephalopathy is manifested by an altered mental state.

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.

Spastic weakness affecting all four limbs.

A type of motor delay characterized by a delay in acquiring the ability to control the large muscles of the body for walking, running, sitting, and crawling.

Complete lack of development of speech and language abilities.

An abnormality of the cerebral cortex with fewer gyri but with normal cortical thickness. This pattern is usually often associated with congenital microcephaly.

An increase in size of the ventricular system of the brain.

A profound delay in the achievement of motor or mental milestones in the domains of development of a child.

Delayed myelination in the central nervous system.

An increase in the level of lactate in the brain identified by magnetic resonance spectroscopy (MRS).

Lack of normal alpha rhythm in the EEG. Alpha rhythm has been defined as a rhythm at 8-13 Hz occurring during wakefulness over the posterior regions of the head, generally with higher voltage over the occipital areas. Amplitude is variable but is mostly below 50 microvolt in adults. It is best seen with eyes closed and under conditions of physical relaxation and relative mental inactivity. It is blocked or attenuated by attention, especially visual and mental effort. One should here note the difference between the terms alpha rhythm and alpha activity

Atrophy of the cortex of the cerebrum.

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.

Muscular hypotonia (abnormally low muscle tone) affecting the musculature of the trunk.

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

Impairment of gas exchange within the lungs secondary to a disease process, neoplasm, or trauma, possibly resulting in hypoxia, hypercarbia, or both, but not requiring intubation or mechanical ventilation. Patients are normally managed with pharmaceutical therapy, supplemental oxygen, or both.

An abnormal buildup of lactic acid in the body, leading to acidification of the blood and other bodily fluids.

An elevated concentration of glycine in the blood.

An increased concentration of alanine in the blood.

Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).

Concentration or activity of the alpha-ketoglutarate dehydrogenase complex as measured in cultured fibroblasts is below the limits of normal. This enzyme is a multienzyme complex consisting of 3 protein subunits, oxoglutarate dehydrogenase, also known as alpha-ketoglutarate dehydrogenase or E1k (EC 1.2.4.2.), dihydrolipoyl succinyltransferase (DLST, or E2k; 126063), and dihydrolipoyl dehydrogenase (DLD, or E3; 238331). The complex catalyzes a key reaction in the Krebs tricarboxylic acid cycle.