Nerve growth factor-tyrosine kinase A pathway is involved in thermoregulation and adaptation to stress: Studies on patients with hereditary sensory and autonomic neuropathy type IV

Neta Loewenthal, Jacov Levy, Ruth Schreiber, Vered Pinsk, Zvi Perry, Zamir Shorer, Eli Hershkovitz

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Hereditary sensory and autonomie neuropathy type IV (HSAN IV) is caused by mutations in the tyrosin kinase A (TrkA) gene, encoding for the high-affinity receptor of nerve growth factor (NGF). The NGF-TrkA system is expressed in many endocrine glands. We hypothesized that HSAN IV represents a natural model for impaired NGF effect on the neuroendocrine system in humans. We have documented the clinical outcome of 31 HSAN IV patients in a single medical center, and investigated their basal endocrine system status. The endocrine system response to thirst was compared between six patients and six healthy children. High rates of mortality (22%) and severe morbidity (30%) have been found in HSAN IV patients. Hypothermia was noted in 40% of the patients and unexplained fever was observed in 56%. Subnormal adrenal function was demonstrated in six (30%) of the patients studied. Furthermore, we found lower plasma norepinephrine (NE) levels in six HSAN IV patients compared with a control group after the thirst test. Our findings emphasize the importance of NGF-TrkA pathway in the physiology of the neuroendocrine system and its response to stress. Inadequate response to stress might contribute to the observed significant mortality, morbidity, and temperature instability in HSAN IV patients.

Original languageEnglish
Pages (from-to)587-590
Number of pages4
JournalPediatric Research
Volume57
Issue number4
DOIs
StatePublished - 1 Apr 2005

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