Reporting from the Hospital for Sick Children, Great Ormono Street, London WC1, the authors have selected 13 cases, 10 boys and 3 girls, with progressive neuronal degeneration of childhood (PNDC) that was complicated by liver disease and confirmed at post mortem in 11. During life, PNDC may be suspected by a characteristic clinical course, abnormal liver function tests, and abnormalities of EEG (grossly asymmetric, very slow activity of high amplitude mixed with polyspikes), VER, and CAT (cortical and central atrophy and areas of low density of the white matter). It is proposed that the term PNDC be reserved for a distinct syndrome characterized by normal initial development followed by developmental retardation and later onset of intractable seizures and liver degeneration, and by autosomal recessive inheritance.

Four patients received sodium valproate; 2 may have died from valproate toxicity although both had abnormal liver enzymes prior to treatment. Phenytoin was probably blameless; 8 patients never received it and the liver pathology of fatty degeneration, necrosis, and cirrhosis was not that expected in phenytoin toxicity.

Brain pathology revealed cortical atrophy with predilection for the calcarine cortex, astrocytic proliferation, and spongy degeneration also involving the thalamus, basal ganglia, and brainstem. Hippocampal sclerosis and cerebellar infarcts resembled epileptic anoxic changes in some patients. [1]

COMMENT: The syndrome of diffuse progressive degeneration of the cerebral gray matter was first described by Alpers in 1931. Ford (1951) differentiated infantile and juvenile types and reported familial cases. Huttenlocher et al (1976) emphasized a coincident hepatic cirrhosis. The cause is unknown. The cerebral pathology resembles anoxic encephalopathy secondary to status epilepticus in some reported cases and the liver disease might be the result of anticonvulsant toxicity, notably sodium valproate. In the author’s cases, however, these causative factors were not generally accepted as primary, and a genetically determined metabolic explanation was preferred.