Arginase 1 Deficiency in Patients Initially Diagnosed with Hereditary Spastic Paraplegia

Research output: Contribution to journalArticlepeer-review


Background: Arginase 1 Deficiency (ARG1-D) is a rare autosomal recessive urea cycle disorder (UCD) characterized by pathologic elevation of plasma arginine and debilitating manifestations. Based on clinical commonalities and low disease awareness, ARG1-D can be diagnosed as hereditary spastic paraplegia (HSP), leading to treatment delays. Cases: A Hispanic woman with unremarkable medical history experienced progressive lower-limb spasticity in her 20s and received a diagnosis of HSP. She developed significant gait abnormalities and is unable to walk without assistance. More recently, two Hispanic brothers with childhood-onset manifestations including lower-limb spasticity, developmental delays, and seizures presented with suspected HSP. All three patients were ultimately diagnosed with ARG1-D based on plasma arginine several-fold above normal levels and loss-of-function ARG1 variants. Disease progression occurred before ARG1-D was correctly diagnosed. Literature Review: Retrospective analyses demonstrate that diagnostic delays in ARG1-D are common and can be lengthy. Because of clinical similarities between ARG1-D and HSP, such as insidious onset and progressive spasticity, accurate diagnosis of ARG1-D is challenging. Timely ARG1-D diagnosis is critical because this UCD is a treatable genetic cause of progressive lower-limb spasticity. Conclusions: Arginase 1 Deficiency should be considered in HSP differential diagnosis until biochemically/genetically excluded, and should be routinely included in HSP gene panels.

Original languageEnglish (US)
Pages (from-to)109-114
Number of pages6
JournalMovement Disorders Clinical Practice
Issue number1
StatePublished - Jan 2023


  • differential diagnosis
  • hyperargininemia
  • inborn error of metabolism
  • spasticity
  • urea cycle disorder

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


Dive into the research topics of 'Arginase 1 Deficiency in Patients Initially Diagnosed with Hereditary Spastic Paraplegia'. Together they form a unique fingerprint.

Cite this