Patients with the classic neonatal PDE experience Seizures soon after birth. In retrospect, many mothers describe rhythmic movements in the uterus (womb) that may start in the late second trimester and which likely represent fetal seizures. Affected neonates frequently have periods of irritability, unusual eye and facial movements, fluctuating tone, and poor feeding (encephalopathy) that precede the onset of clinical seizures. Abnormal Apgar scores (which measure heart rate, respiration, muscle tone, reflex Irritability and color at birth plus one minute and at birth plus five minutes) and cord blood gases may also be seen. Under such conditions, it is not uncommon for these infants to be diagnosed initially as laboring under insufficient oxygen with consequent damage to the nervous system. Similar periods of encephalopathy may be seen in older infants with PDE, particularly prior to the onset of a recurrence of clinical seizures. Pyridoxine-treated patients who have been lax in taking their medicine (non-compliant) or those patients whose daily vitamin requirement may have increased due to growth or an intercurrent infection (particularly Fever or gastroenteritis) may also experience recurrent seizures.
Many atypical presentations of PDE have been described. These include late onset Seizures (up to two years of age, and in very rare instances into adolescence), Seizures which initially respond to anticonvulsant drugs and then become intractable, Seizures during early life which do not respond to pyridoxine but which then come under control with pyridoxine several months later, and patients with prolonged seizure-free intervals (up to 5.5 months) which occur after discontinuing pyridoxine.
Patients with PDE may have various types of clinical seizures. While dramatic presentations consisting of prolonged Seizures and/or recurrent episodes of shorter Seizures associated with a long-lasting loss of consciousness (status epilepticus) are considered to be the typical feature of affected individuals, PDE patients may also have recurrent self-limited events including partial seizures, generalized seizures, atonic seizures, myoclonic events and infantile spasms. On EEG, patients with PDE may also have electrographic Seizures without clinical correlates.
A variable degree of Intellectual disability is common in these patients. Patients whose Seizures appear earlier in life are more likely to show diminished cognitive function. Some clinical reports conclude that the length of the delay in diagnosis and initiation of effective pyridoxine treatment may be related to increased handicaps. Future cognitive function is also likely related to the type of genetic mutation underlying PDE in a particular patient, as well as any associated abnormalities in brain development. Few formal psychometric assessments in patients with PDE have been performed. The limited studies performed to date indicate that in these patients verbal intellectual function is more impaired than non-verbal skills. While significant neurodevelopmental disabilities and psychiatric disorders may be present in some PDE patients, it is important that parents know that patients with PDE may have normal intellectual function.