Klüver-Bucy syndrome associated with a recessive variant in HGSNAT in two siblings with Mucopolysaccharidosis type IIIC (Sanfilippo C).
Klüver-Bucy syndrome (KBS) comprises a set of neurobehavioral symptoms with psychic blindness, hypersexuality, disinhibition, hyperorality, and hypermetamorphosis that were originally observed after bilateral lobectomy in Rhesus monkeys. We investigated two siblings with KBS from a consanguineous family by whole-exome sequencing and autozygosity mapping. We detected a homozygous variant in the heparan-α-glucosaminidase-N-acetyltransferase gene (HGSNAT; c.518G>A, p.(G173D), NCBI ClinVar RCV000239404.1), which segregated with the phenotype. Disease-causing variants in this gene are known to be associated with autosomal recessive Mucopolysaccharidosis type IIIC (MPSIIIC, Sanfilippo C). This lysosomal storage disease is due to deficiency of the acetyl-CoA:α-glucosaminidase-N-acetyltransferase, which was shown to be reduced in patient fibroblasts. Our report extends the phenotype associated with MPSIIIC. Besides MPSIIIA and MPSIIIB, due to variants in SGSH and NAGLU, this is the third subtype of Sanfilippo disease to be associated with KBS. MPSIII should be included in the differential diagnosis of young patients with KBS.
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Hao
H
Hu
Department of Neuropediatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Christoph
C
Hübner
Metabolic Unit, University Hospital Hamburg-Eppendorf, Hamburg, Germany.
Zoltan
Z
Lukacs
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Luciana
L
Musante
NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Esther
E
Gill
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Thomas F
TF
Wienker
Max Planck Institute for Molecular Genetics, Berlin, Germany.
Hans-Hilger
HH
Ropers
Department of Neuropediatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.|NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Ellen
E
Knierim
Department of Neuropediatrics, Charité-Universitätsmedizin Berlin, Berlin, Germany.|NeuroCure Clinical Research Center, Charité-Universitätsmedizin Berlin, Berlin, Germany.
Markus
M
Schuelke
D000123:Acetyltransferases / Q000235:genetics*; D002648:Child; D059472:Exome; D005260:Female; D005808:Genes, Recessive; D006720:Homozygote; D006801:Humans; D020232:Kluver-Bucy Syndrome / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D009084:Mucopolysaccharidosis III / Q000150:complications / Q000175:diagnosis / Q000235:genetics*; D010641:Phenotype; D035781:Siblings
D000123:Acetyltransferases; C514442:HGSNAT protein, human