PT  - JOURNAL ARTICLE
AU  - Willem M A Verhoeven
AU  - Jos I M Egger
AU  - Paddy K C Janssen
AU  - Arie van Haeringen
TI  - Adult male patient with severe intellectual disability caused by a homozygous mutation in the HNMT gene
AID  - 10.1136/bcr-2020-235972
DP  - 2020 Dec 01
TA  - BMJ Case Reports
PG  - e235972
VI  - 13
IP  - 12
4099  - http://casereports.bmj.com/content/13/12/e235972.short
4100  - http://casereports.bmj.com/content/13/12/e235972.full
SO  - BMJ Case Reports2020 Dec 01; 13
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.