Neurologic crises in 48 children with tyrosinemia identified on neonatal screening since 1970 are described from the Departments of Genetics, Hopital Sainte Justine, Hopital de Chicoutimi; and Universite Laval, Quebec, Canada. Neurologic crises had occurred in 20 (42%) and began at a mean age of one year leading to 104 hospital admissions. Abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (75%), vomiting or paralytic ileus (69%), muscle weakness (29%), and self-mutilation (8%). Fourteen patients died due to complications of respiratory insufficiency or mechanical ventilation. In 5 patients undergoing hepatic transplantation none had neurologic crises. Urinary excretion of gamma aminolevulinic acid, an intermediate of porphyrin biosynthesis, was elevated during crises and during asymptomatic periods. Axonal degeneration and demyelination were demonstrated by EMG, NCS and neuromuscular biopsies. [1]

COMMENT. This study indicates that episodes of acute severe peripheral neuropathy are common in hereditary tyrosinemia and resemble crises of the neuropathic porphyrias. Hepatic transplantation eliminated the neurologic crisis, the major cause of mortality in these patients.

Abnormal porphyrin metabolism appears to underlie the neurologic crisis of tyrosinemia and is associated with elevated gamma aminolevulinic acid excretion. Therapy for the neurologic crises included adequate caloric intake, respiratory support, and control of pain, hypertension, hyponatremia, and self-mutilation. Gavage with high carbohydrate, high calorie feeds without phenylalanine or tyrosine were employed. Barbiturates and other agents contraindicated in porphyria were avoided.