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Neurologic crises in hereditary tyrosinemia
G Mitchell1, J Larochelle, M Lambert
1Department of Genetics, Hôpital Sainte Justine, Montreal, PQ, Canada.
The New England Journal of Medicine
|February 15, 1990
Summary
Hereditary tyrosinemia frequently causes severe neurologic crises in children, characterized by pain, weakness, and paralysis. These episodes of peripheral neuropathy are common and can be fatal, highlighting a critical but often overlooked aspect of the disease.
Area of Science:
- Biochemistry
- Neurology
- Genetics
Background:
- Hereditary tyrosinemia is a metabolic disorder affecting tyrosine breakdown.
- It commonly leads to liver and kidney failure, and cancer.
- Neurologic symptoms are known but often underestimated.
Purpose of the Study:
- To describe the frequency and characteristics of neurologic crises in children with hereditary tyrosinemia.
- To investigate potential biochemical markers for these crises.
- To understand the underlying pathology of the neurologic manifestations.
Main Methods:
- Retrospective analysis of 48 children with hereditary tyrosinemia identified via neonatal screening since 1970.
- Clinical evaluation of neurologic crisis symptoms, hospital admissions, and outcomes.
- Biochemical analysis of blood and urine, including tyrosine, succinylacetone, aminotransferases, and delta-aminolevulinic acid.
- Electrophysiologic studies and neuromuscular biopsies in affected patients.
Main Results:
- 20 out of 48 children (42%) experienced neurologic crises starting around age one.
- Crises involved severe pain, hypertonia, vomiting, weakness, and self-mutilation, leading to 104 hospital admissions.
- Eight children needed mechanical ventilation; 14 died. Survivors typically recovered between episodes.
- No reliable biochemical marker was identified; delta-aminolevulinic acid was elevated but not specific.
- Pathology revealed axonal degeneration and demyelination.
Conclusions:
- Acute, severe peripheral neuropathy is a common and serious complication of hereditary tyrosinemia.
- These neurologic crises share similarities with those seen in neuropathic porphyrias.
- Early recognition and management of these neurologic events are crucial for improving outcomes in hereditary tyrosinemia.