Arginase 1 Deficiency in Patients Initially Diagnosed with Hereditary Spastic Paraplegia.

Abstract

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.

• Authors: Markey C McNutt, Nathan Foreman, Garrett Gotway
• Journal: Movement disorders clinical practice (Mov Disord Clin Pract) Vol. 10 Issue 1 Pg. 109-114 (Jan 2023) ISSN: 2330-1619 [Electronic] United States
• PMID: 36698992 (Publication Type: Journal Article, Review)
• Copyright: © 2022 The Authors. Movement Disorders Clinical Practice published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.