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IEMbase 0550: SLC33A1-related acetyl-CoA transporter deficiency

Scope

Field Value
IEMbase ID 550
Nosology 22.1.05.01
Gene SLC33A1
External IDs OMIM:614482; ORPHA:300313
Generated mapping MAPPED; Huppke-Brendel_syndrome.yaml
Candidate DisMech targets Huppke-Brendel_syndrome.yaml
Review date 2026-07-07

IEMbase phenotype signal

IEMbase represents SLC33A1-related acetyl-CoA transporter deficiency, with alternate labels congenital cataracts, hearing loss, low serum copper and ceruloplasmin, Huppke-Brendel syndrome, and CCHLND. The record is autosomal recessive, and treatability is unknown. No treatment rows are listed.

The biochemical signal is decreased serum ceruloplasmin and decreased serum copper. Clinical rows include congenital cataract, hearing loss, hypomyelination on MRI, axial muscular hypotonia, cerebellar atrophy, and cerebral atrophy.

DisMech phenotype coverage

Huppke-Brendel_syndrome.yaml is the correct local target. The local entry models biallelic SLC33A1 variants causing AT-1 acetyl-CoA transporter deficiency in the endoplasmic reticulum, defective secretory-pathway acetylation, reduced ceruloplasmin secretion, secondary low serum copper, and a severe neurodevelopmental syndrome with congenital cataracts, hearing loss, developmental delay, cerebellar hypoplasia, and hypomyelination.

The local file also distinguishes the low copper/ceruloplasmin pattern from primary copper deficiency and Wilson disease mimicry.

Concordance and completeness

Judgement: correct high-concordance mapping to Huppke-Brendel_syndrome.yaml.

IEMbase and DisMech agree on SLC33A1 identity, recessive inheritance, AT-1 / acetyl-CoA transporter scope, low serum copper, low ceruloplasmin, congenital cataracts, hearing loss, hypomyelination, and hypotonia. DisMech is stronger for the secretory-pathway acetylation and ceruloplasmin-secretion mechanism.

IEMbase adds compact age-patterned prompts for cerebellar and cerebral atrophy and specifies axial muscular hypotonia.

Curation actions

  • Keep this record mapped to Huppke-Brendel_syndrome.yaml.
  • Consider adding the IEMbase cerebral/cerebellar atrophy and axial-hypotonia wording if supported by existing evidence.
  • Preserve low serum copper as secondary to low ceruloplasmin, not as primary copper deficiency.