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Page 37
May 20-21, 2019 | Rome, Italy
Journal Clinical Psychiatry and Cognitive Psychology | Volume 3
OF EXCELLENCE
IN INTERNATIONAL
MEETINGS
YEARS
Psychiatry 2019
PSYCHIATRY AND
PSYCHOLOGICAL DISORDERS
2nd International Conference on
Monika H Seltenhammer et al., J Clin Psychiatry Cog Psychol 2019, Volume 3
LESCH-NYHAN SYNDROME AND CHILDREN´S MALTREATMENT FORENSIC VERIFICA-
TION OF A RARE INBORN ERROR METABOLIC DISEASE
Monika H Seltenhammer1, Ulrike Resch2, Ursula Windberger3, Chantal Rodgarkia-Dara4, Martin
Kraupp5, Sini Junttila6, Carmen Czepe6 and Andrea M Berzlanovich1
1 Center for Forensic Medicine, Medical University of Vienna, Austria
2 Center for Physiology and Pharmacology, Medical University of Vienna, Austria
3 Center for Biomedical Research, Medical University of Vienna, Austria
4 THP Medical Products, Austria
5 Department of Medical Chemistry, Medical University of Vienna, Austria
6 The Vienna Biocenter Core Facilities GmbH, Austria
Lesch-Nyhan syndrome (LNS) is characterized by neurologic dysfunction, significant cognitive impairment as
well as behavioral disturbances and uric acid overproduction. This rare X-linked inborn genetic disorder is
caused by distinct various mutations in the gene encoding the purine biosynthetic HPRT-1 (Hypoxanthine-gua-
nine phosphoribosyltransferase-1) enzyme. Depending on the degree of mutations, LNS results in more or less
complete deficiency of this enzyme, which catalyzes the conversion hypo-xanthine to inosine monophosphate
(IMP) and guanine to Guanosine monophosphate (GMP). Thus, the deficiency of HPRT activity leads to exces-
sive uric acid production accompanied by (juvenile) gout. The major hallmark of the disease is a persistent
self-injurious behavior due to profound neurological disruptions. HPRT is reasonably supposed to have pleio-
tropic effects on disparate genes and signal transduction pathways within the neuronal system. Furthermore,
here, researchers report about the only one known case of death diagnosed as LNS in Austria. According to the
medical history, the disease was already proven in the lifetime of the boy. Owning to children’s maltreatment
as an essential differential diagnosis of LNS the prosecution ordered a forensic autopsy. Additional examina-
tions with regard to the anamnesis were carried out: Neuropathological-microscopic findings were described,
HPRT-enzyme activity was determined (in comparison with non-LNS cases), micro-RNA and mutation analysis
(NGS sequencing) as well as immunohistochemical approaches were performed. Typical lesions due to distinct
self-injuries could be described. HRPT-1-enzyme activity completely failed, suggesting a severe phenotype
with pronounced mutations. This fact has been independently proven by negative immunohistochemistry of
the HRPT-1 enzyme. Finally, we identified typical micro-RNA signature for our case and characteristic mutations
leading to this severe phenotype. Due to the rareness of this neurogenetic syndrome, every single case may
serve as an important piece of the puzzle in the concept of elucidation of the molecular and cellular basis of
LNS and might be also applicable to other ill-defined rare inborn error metabolic diseases.
Monika H Seltenhammer completed her DVM and PhD from Medical University of Vienna, Austria and Postdoctoral studies from
University of Veterinary Medicine, Max Perutz Laboratories and Medical University of Vienna, Austria, where her core area of scien-
tific work mainly consisted in cancer research (melanoma) and pathology but also immunology, neurology and virology. She has
received several honor and awards. She is a leading member of the scientific staff of Dr. Daniele Ugo Risser at the Department of
Forensic Medicine of the Medical University Vienna, where she specializes in neurobiology and addiction behavior.
BIOGRAPHY