Huppke-Brendel syndrome in a seven months old boy with a novel 2-bp deletion in SLC33A1

Metab Brain Dis. 2016 Oct;31(5):1195-8. doi: 10.1007/s11011-016-9854-6. Epub 2016 Jun 15.


Huppke -Brendel syndrome is a new addition to the evolving spectrum of copper metabolism defects. It is an autosomal recessive disorder characterized by congenital cataract, impaired hearing, and developmental delay with low copper and ceruloplasmin. It is caused by defects in SLC33A1 that codes for acetyl CoA transporter protein. Reports on variation in this gene causing human disease is extremely scarce and the metabolic link between this gene and copper metabolism is yet to be identified. Here we report a seven months old infant with Huppke-Brendel Syndrome. In addition to the already reported features, he also had hypo pigmented hair and hypogonadism. His magnetic resonance imaging revealed hypo myelination and cerebellar hypoplasia. Clinical exome sequencing revealed a homozygous two base pair deletion, c.542_543delTG (p.Val181GlyfsTer6) in exon 1 of the SLC33A1. This report expands the phenotypic and genotypic spectrum of Huppke Brendel syndrome.

Keywords: Acetyl co a transporter; Ceruloplasmin; Congenital cataract; Copper; Hypo- myelination; SLC33A1.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Pairing / genetics*
  • Cerebellum / abnormalities
  • Cerebellum / metabolism
  • Ceruloplasmin / genetics
  • Ceruloplasmin / metabolism
  • Copper / metabolism*
  • Developmental Disabilities / diagnosis
  • Developmental Disabilities / genetics
  • Developmental Disabilities / metabolism
  • Fatal Outcome
  • Humans
  • Infant
  • Male
  • Membrane Transport Proteins / genetics*
  • Metabolic Diseases / diagnosis
  • Metabolic Diseases / genetics*
  • Metabolic Diseases / metabolism*
  • Nervous System Malformations / diagnosis
  • Nervous System Malformations / genetics
  • Nervous System Malformations / metabolism
  • Pedigree
  • Sequence Deletion / genetics*
  • Syndrome


  • Membrane Transport Proteins
  • SLC33A1 protein, human
  • Copper
  • Ceruloplasmin

Supplementary concepts

  • Cerebellar Hypoplasia