RT Journal Article
SR Electronic
T1 Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene
JF BMJ Case Reports
JO BMJ Case Reports
FD BMJ Publishing Group Ltd
SP e235972
DO 10.1136/bcr-2020-235972
VO 13
IS 12
A1 Willem M A Verhoeven
A1 Jos I M Egger
A1 Paddy K C Janssen
A1 Arie van Haeringen
YR 2020
UL http://casereports.bmj.com/content/13/12/e235972.abstract
AB Histamine is involved in various physiological functions like sleep–wake cycle and stress regulation. The histamine N-methyltransferase (HNMT) enzyme is the only pathway for termination of histamine neurotransmission in the central nervous system. Experiments with HNMT knockout mice generated aggressive behaviours and dysregulation of sleep–wake cycles. Recently, seven members of two unrelated consanguineous families have been reported in whom two different missense HNMT mutations were identified. All showed severe intellectual disability, delayed speech development and mild regression from the age of 5 years without, however, any dysmorphisms or congenital abnormality. A diagnosis of mental retardation, autosomal recessive 51 was made. Here, we describe a severely mentally retarded adolescent male born from second cousins with a homozygous mutation in HNMT. His phenotypic profile comprised aggression, delayed speech, autism, sleep disturbances and gastro-intestinal problems. At early age, regression occurred. Treatment with hydroxyzine combined with a histamine-restricted diet resulted in significant general improvement.