[A case of spastic paraplegia 48 with a novel mutation in the AP5Z1 gene]

Rinsho Shinkeigaku. 2020 Aug 7;60(8):543-548. doi: 10.5692/clinicalneurol.60.cn-001419. Epub 2020 Jul 7.
[Article in Japanese]


We describe an additional patient with spastic paraplegia 48 (SPG48). A 52-year-old woman with gradually increasing gait disturbance was admitted to our hospital. When she was 47 years old, acquaintances noted a shuffling gait. Gait worsening was evident at 48 years. Spastic gait was apparent at 50, and she required a walking stick at 54. Her elder brother had similar gait disturbance. No consanguinity was known. Neurologic examination at 52 disclosed spasticity and moderate weakness in the lower limbs. Spasticity and brisk reflexes in all limbs. Laboratory studies including HTLV-1 titer detected no abnormalities. MRI demonstrated mild corpus callosum narrowing and prominent anterior periventricular hyperintensities in fluid attenuation inversion recovery images. In limb muscles, electromyography (EMG) showed a chronic neurogenic pattern including reduced interference. Gene analysis identified compound homozygosity in exon 7 of adaptor-related protein complex 5 subunit zeta 1 (AP5Z1), including a novel frameshift mutation, c.1662_1672del;p.Glu554Hfs*15 in the patient, and a heterozygous missense mutation in asymptomatic family members, including her mother, two siblings, and a daughter. The frameshift mutation is considered a pathogenic variant according to American College of Medical Genetics and Genomics standards and guidelines. Based on clinical features, imaging findings and genetic abnormalities, we diagnosed this patient with SPG48. Mutations in AP5Z1, which encodes the ζ subunit of AP-5, underlie SPG48. The AP-5 adaptor protein complex, which is mutated in SPG48, binds to both spastizin and spatacsin. While hereditary spastic paraplegias generally are clinically and genetically heterogenous, SPG48, SPG11, and SPG15 are clinically similar.

Keywords: adaptor-related protein complex 5 subunit zeta 1 (AP5Z1); autosomal recessive; corpus callosum narrowing; hereditary spastic paraplegia; spastic paraplegia 48 (SPG48).

Publication types

  • Case Reports
  • Review

MeSH terms

  • Adaptor Proteins, Vesicular Transport / genetics*
  • Cerebral Ventricles / diagnostic imaging
  • Cerebral Ventricles / pathology
  • Corpus Callosum / diagnostic imaging
  • Corpus Callosum / pathology
  • Female
  • Frameshift Mutation*
  • Gait Disorders, Neurologic / etiology
  • Genes, Recessive
  • Homozygote
  • Humans
  • Magnetic Resonance Angiography
  • Male
  • Middle Aged
  • Paraparesis, Spastic / complications
  • Paraparesis, Spastic / genetics*


  • AP5Z1 protein, human
  • Adaptor Proteins, Vesicular Transport