DIAGNOSING
ARGINASE 1 DEFICIENCY

Early and accurate diagnosis of
Arginase 1 Deficiency is crucial1-3

The key to making a definitive diagnosis

Persistently elevated levels of arginine distinguish ARG1‑D from other neurometabolic and neurologic disorders4

  • ARG1‑D may be misdiagnosed as CP or HSP at initial presentation, as these diseases have overlapping manifestations5

Delays in diagnosis are associated with poor clinical outcomes in patients with ARG1‑D1-3,6

  • Delays in diagnosis during childhood may lead to disease progression and worse clinical outcomes as an adult1-3,6
  • Hyperammonemia is not a hallmark of ARG1‑D, and acute episodes of hyperammonemia occur infrequently7-9
Differential diagnosis of Arginase 1 Deficiency (ARG1‑D).

High plasma arginine levels are the key to differentiating ARG1‑D
from other UCDs, CP, and HSP4,9

THE IMPACT OF A MISSED DIAGNOSIS

Delays in diagnosis are common, leading to disease progression and worse clinical outcomes1,5

ARG1‑D can be diagnosed in patients of all ages, from infancy and toddlerhood to adolescence and adulthood

Due to limitations of newborn
screening, ARG1‑D may be missed10,11

  • Determining arginine cutoff levels in screening is problematic as the transfer of metabolites, such as arginine, from mother to baby may compromise testing10,11
  • Screening algorithms and arginine cutoff levels vary10
  • ARG1‑D is not routinely a primary screening target2,10

Delays in diagnosis have been reported (mean delay of 4.3 years [range 0–20 years])1

In its initial presentation, 3 major manifestations of ARG1‑D appear in early childhood:

  • Lower and upper limb spasticity1,5
  • Seizures1,5
  • Global developmental delay/intellectual disability1,5

Newborn screening for ARG1‑D is not routinely performed in many US states and testing is inconsistent, causing potential delays in diagnosis2,10

ARG1‑D may be misdiagnosed as CP or HSP at initial presentation, due to the presence of overlapping manifestations5

Inconsistent newborn screening per state, variable screening algorithms, and lack of disease awareness may also cause delays in diagnosis1,2,10

Delays in diagnosis coupled with late onset of manifestations led to initial intervention at ~6 years of age1,*

*A hypothesis-generating study of physician responses in a cohort of 19 patients with ARG1‑D (13 male, 6 female, ranging from 1 to 45 years) compared with a matched control of 19 healthy patients (12 male, 7 female, ranging from 1 to 44 years).1

DIAGNOSING ARG1‑D

Key manifestations

  • Progressive spasticity5,12-14
  • Aversion to protein1,5,14
  • Impaired mobility/gait5,12,14

AND/OR

Medical history

  • Atypical CP5
  • Idiopathic spasticity5,15
  • HSP with unknown etiology5
  • Episodes of hyperammonemia1,12

Other manifestations may include:

Neurological

  • Seizures5,7
  • Speech impairment5,16
  • Intellectual disability5,7,12

Developmental

  • Global developmental delay5
  • Behavioral abnormalities1,12
  • Learning disabilities5

Functional

  • Lower and upper limb spasticity1,12
  • Toe walking1,12
  • Growth impairment5,12,15

ELEVATED LEVELS OF ARGININE ARE THE HALLMARK OF ARG1‑D4

Evaluate the results of a plasma amino acid panel for high levels of plasma arginine (>115 μmol/L)17

If high levels of plasma arginine are present, confirm with a genetic test†

†Due to the genetic heterogeneity of ARG1 genotypes, not all mutations causing ARG1‑D have been identified.

Recognizing the manifestations of ARG1‑D in your practice

  • Evaluate complete medical, dietary, family, and social history, and perform a thorough physical exam

The importance of a geneticist on the care team

  • Diagnosis can be readily made by measuring plasma arginine levels and confirmed with a genetic test
  • Specialists who manage ARG1‑D include a metabolic or genetic specialist

If you suspect your patient may have ARG1‑D, confirm a diagnosis with the THINK ARGININE™ Diagnostic Program

Do you suspect your patient may have ARG1‑D?

Symptom Navigator

The Symptom Navigator can help you learn more
and connect you to information and resources.

Order a no-charge genetic test for your patients‡

If your patient received newborn screening results that may indicate ARG1‑D, confirm the diagnosis with genetic testing.

‡Eligibility requirements apply.

TESTING FOR ARGINASE 1 DEFICIENCY§

Diagnostic testing can be ordered for any patient 40 years or younger living in the US who is suspected of having
Arginase 1 Deficiency (ARG1‑D) based on:

of the following:

Elevated arginine valueǁ

Presumptive positive newborn
screening for ARG1‑Dǁ

Family history of ARG1‑D

OR at least 2 of the following:

Protein aversion
Seizures

Spasticity
Progressive loss of ambulation

Global developmental delay

§Eligibility requirements apply.

ǁDocumentation required.

The THINK ARGININE™ Diagnostic Program provides access to no-charge
sponsored genetic testing and services for ARG1‑D patients and physicians

If your patient received newborn screening results that may indicate ARG1‑D, confirm the
diagnosis with genetic testing.

Early detection has its advantages

  • Early intervention has been shown to have a positive impact later in life2,3
Arginase 1 Deficiency (ARG1‑D) - order amino acid panel and genetic test

If you suspect your patient may have ARG1‑D

Early diagnosis of ARG1‑D could potentially reduce the burden
of the disease.2,3 Order a no-charge sponsored genetic test*

*Eligibility requirements apply.

References:
1. Huemer M et al. J Inherit Metab Dis. 2016;39:331-340. 2. Diez-Fernandez C et al. Hum Mutat. 2018;39:1029-1050. 3. Edwards RL et al. J Inherit Metab Dis. 2009;32:S197-S200. 4. De Deyn PP et al. In: De Deyn PP et al, eds. Guanidino Compounds in Biology and Medicine. London, UK: John Libbey & Company Ltd; 1997:53-69. 5. Carvalho DR et al. Pediatr Neurol. 2012;46:369-374. 6. Bakhiet M et al. Medicine (Baltimore). 2018;97:e10780. 7. NORD. The Physician’s Guide to Urea Cycle Disorders. 2012. https://www.filiere-g2m.fr/images/NORD_Physician_Guide_to_Urea_Cycle_Disorders.pdf. Accessed August 26, 2022. 8. Scaglia F, Lee B. Am J Med Genet C Semin Med Genet. 2006;142C:113-120. 9. Burrage LC et al. Hum Mol Genet. 2015;24:1-11. 10. Therrell BL et al. Mol Genet Metab. 2017;121:308-313. 11. Pitt JJ. Clin Biochem Rev. 2010;31:57-68. 12. Crombez EA, Cederbaum SD. Mol Genet Metab. 2005;84:243-251. 13. Cai X et al. Medicine (Baltimore). 2018;97:e9880. 14. Sin YY et al. J Mol Med (Berl). 2015;93:1287-1296. 15. Prasad AN et al. J Child Neurol. 1997;12:301-309. 16. Sun A et al. In: Adam MP et al, eds. GeneReviews®. Seattle, WA: University of Washington, Seattle; 2020. https://www.ncbi.nlm.nih.gov/books/NBK1159/. Accessed July 15, 2022. 17. Lüneburg N et al. J Nutr. 2011;141:2186-2190.