Neurological, Neurodevelopmental and Treatment Outcomes in Patients With Pyruvate Dehydrogenase Complex Deficiency
ABSTRACT Objective The aim of this study was to characterize intellectual and motor function, neurological features including epilepsy, treatment response, and adaptive behavior in patients with pyruvate dehydrogenase complex deficiency (PDCD) in Sweden. Methods Forty‐two individuals with genetically confirmed PDCD (86% PDHA1‐related disease) were identified from a nationwide epidemiological study and were included in this cross‐sectional study comprising systematic neurological evaluations (n = 41) and caregiver interviews assessing adaptive behavior (n = 35). Results Intellectual disability was detected in 33/42 (79%) individuals, while 31/35 (89%) demonstrated significant impairments in adaptive functioning. Although 27/39 (69%) were ambulatory, only 8/39 (21%) demonstrated age‐appropriate walking ability. Clinical signs of polyneuropathy were observed in 24/41 (59%), bulbar symptoms in 22/41 (54%), spasticity in 19/41 (46%), ataxia in 13/41 (32%), and dystonia in 9/41 (22%). Lifetime epilepsy was present in 16/41 (39%) of individuals. Ketogenic diet treatment, administered to 30 individuals, was effective in both prenatal‐ and postnatal‐onset disease. Seizure frequency decreased in individuals with epilepsy (8/9; 89%) and relapses of dystonia, ataxia, exercise intolerance, and lactic acidosis were prevented in all affected individuals (15/15). Improvements in communication and motor function were also noted. Discussion Intellectual disability and deficits in adaptive behavior are frequent in PDCD, although cognitive outcomes are more heterogeneous among individuals with postnatal onset. Prenatal onset and epilepsy are associated with severe‐profound intellectual disability. Although most are ambulatory, motor deficits are frequent. A ketogenic diet treatment is a safe and effective therapeutic option, contributing to both seizure control and remission of neurological deterioration relapses.