Neurologic crises in hereditary tyrosinemia.

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  • Additional Information
    • Source:
      Publisher: Massachusetts Medical Society Country of Publication: United States NLM ID: 0255562 Publication Model: Print Cited Medium: Print ISSN: 0028-4793 (Print) Linking ISSN: 00284793 NLM ISO Abbreviation: N Engl J Med Subsets: MEDLINE
    • Publication Information:
      Original Publication: Boston, Massachusetts Medical Society.
    • Subject Terms:
      Amino Acid Metabolism, Inborn Errors/*complications ; Peripheral Nervous System Diseases/*etiology ; Tyrosine/*blood; Acute Disease ; Adolescent ; Adult ; Amino Acid Metabolism, Inborn Errors/pathology ; Amino Acid Metabolism, Inborn Errors/therapy ; Aminolevulinic Acid/blood ; Child ; Child, Preschool ; Humans ; Hypesthesia/etiology ; Intestinal Pseudo-Obstruction/etiology ; Muscle Hypertonia/etiology ; Pain/etiology ; Peripheral Nerves/pathology ; Self Mutilation/etiology ; Vomiting/etiology
    • Abstract:
      Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.
    • Accession Number:
      42HK56048U (Tyrosine)
      88755TAZ87 (Aminolevulinic Acid)
    • Publication Date:
      Date Created: 19900215 Date Completed: 19900306 Latest Revision: 20220311
    • Publication Date:
      20240829
    • Accession Number:
      10.1056/NEJM199002153220704
    • Accession Number:
      2153931