<unk>  is characterized by an array of signs and symptoms including mental and motor developmental delays, infantile seizures refractory to anticonvulsants, ataxia, dystonia, dysarthria, opsoclonus, spasticity, other paroxysmal neurologic phenomena and sometimes deceleration of head growth also known as microcephaly. The presence and severity of symptoms vary considerably between affected individuals. Individuals with the disorder generally have frequent seizures (epilepsy), often beginning in the first months of life. In newborns, the first sign of the disorder may be involuntary eye movements that are rapid and irregular. Patients typically begin to experience seizures between three and six months of age, but some occur much later. Other seizure types may occur, including generalized tonic clonic, focal, myoclonic, atypical absence, atonic, or unclassified. Mothers of infants with this disorder usually have uneventful pregnancies and deliveries, with the child appearing normal and within typical birth weight and length ranges. Infants with<unk>  syndrome have a normal head size at birth, but the growth of the brain and skull is slow, in severe cases resulting in an abnormally small head size (microcephaly). Typically, seizures start between one and four months in 90% of cases with abnormal eye movements and apneic episodes preceding the onset of seizures in some cases. Seizures usually are complex to begin with and later become more generalized. Seizure frequency is variable and a history of decreasing frequency during times of ketosis may prompt a diagnosis. It is estimated that 10% of individuals with<unk>  do not have seizures and symptoms are typically less severe in these cases. Most of these non-epileptic cases will still have developmental delay, intellectual delays, and movement disorders such as ataxia, alternating hemiplegia, or dystonia. Some symptoms may be present all the time (like walking difficulties), while other signs may come and go (like seizures or poor balance). These findings can be clustered under three major domains: cognition, behavior and movement. Effects The syndrome can cause infantile seizures refractory to anticonvulsive drugs, developmental delay, acquired microcephaly and neurologic manifestations including spasticity, hypotonia, and ataxia. The frequency, severity, and types of seizures may vary considerably among<unk>  patients and do not necessarily correspond to the severity of other symptoms. Most seizures in<unk>  patients are not easily treated with anti-seizure medications. A minority of<unk>  patients (approximately 10%) do not experience seizures. Cognitive symptoms often become apparent as developmental milestones are delayed. Cognitive deficits range from subtle learning difficulties to severe intellectual disabilities. Often speech and language are impaired. Behavioral symptoms affect relations with other people and may include short attention span, intractability, and delays in achieving age-appropriate behaviors. Sociability with peers, however, is a strength in<unk>  patients. Movement symptoms relate to the quality of motor functions. Walking may be delayed or difficult because legs are stiff (spasticity), balance is poor (ataxia) or posture is twisted (dystonia). Fine motor deficits may affect speech quality and manipulative skills, such as writing. These abnormalities may be constant or intermittent (paroxysmal). Paroxysmal exercise-induced dyskinesia (PED) may also be present. Other intermittent symptoms may include headaches, confusion, and loss of energy. Episodes of confusion, lack of energy/stamina, and/or muscle twitches may occur; particularly during periods without food. Some young patients experience occasional abnormal eye movements that may resemble opsoclonus or nystagmus. The rapid eye movements that some<unk> 1 patients exhibit are rapid, multidirectional, and there is often a head movement in the same direction as the eye movement. These abnormal eye movements were recently named aberrant gaze saccades. Hemiplegia or alternating intermittent hemiplegia may occur in some patients and mimic stroke-like symptoms. Another characteristic of<unk>  is that symptoms are sensitive to food (e.g. symptoms that can be temporarily improved by intake of carbohydrates), and symptoms may be worse in the morning upon and just after waking. All symptoms may be aggravated or triggered by factors such as hunger, fatigue, heat, anxiety, and sickness. The symptom picture for each patient may evolve and change over time as children with<unk>  grow and develop through adolescence and into adulthood. Data on adult<unk> DS are just emerging. Changes in symptomatology over time include a shift from infantile-childhood onset epilepsy to adolescent-adult onset movement disorders including PED.
GLUT1 deficiency
Glutaminase deficiency
Glycerol kinase deficiency
WNT4 deficiency
Multiple carboxylase deficiency
Pyruvate kinase deficiency
2,4 Dienoyl-CoA reductase deficiency
NGLY1 deficiency