Mutations in DDHD1, encoding a phospholipase A1, is a novel cause of retinopathy and neurodegeneration with brain iron accumulation

Eur J Med Genet. 2017 Dec;60(12):639-642. doi: 10.1016/j.ejmg.2017.08.015. Epub 2017 Aug 14.

Abstract

Defects of phospholipids remodelling and synthesis are inborn errors of metabolism responsible for various clinical presentations including spastic paraplegia, retinopathy, optic atrophy, myo- and cardiomyopathies, and osteo-cutaneous manifestations. DDHD1 encodes a phospholipase A1, which is involved in the remodelling of phospholipids. We previously described a relatively pure hereditary spastic paraplegia (HSP) phenotype associated with mutations in DDHD1. Here we report a complex form of HSP associated with retinal dystrophy and a pattern of neurodegeneration with brain iron accumulation (NBIA) on brain MRI, due to a novel homozygous mutation in DDHD1. This observation enlarges the clinical spectrum of DDHD1-associated disorders and sheds light on a new aetiology for syndromes associating retinopathy and NBIA. It also emphasizes the role of complex lipids in the retina.

Keywords: DDHD1; Hereditary spastic paraplegia; NBIA; Phospholipids; Retinopathy.

Publication types

  • Case Reports

MeSH terms

  • Brain / diagnostic imaging
  • Homozygote
  • Humans
  • Iron Metabolism Disorders / diagnosis
  • Iron Metabolism Disorders / genetics*
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mutation*
  • Neuroaxonal Dystrophies / diagnosis
  • Neuroaxonal Dystrophies / genetics*
  • Optic Atrophies, Hereditary / diagnosis
  • Optic Atrophies, Hereditary / genetics*
  • Phospholipases A1 / genetics*
  • Spastic Paraplegia, Hereditary / diagnosis
  • Spastic Paraplegia, Hereditary / genetics*
  • Syndrome

Substances

  • Phospholipases A1

Supplementary concepts

  • Neurodegeneration with brain iron accumulation (NBIA)