What are the other Names for this Condition? (Also known as/Synonyms)

• ACY1 Deficiency Disorder
• ACY1D Disorder
• Deficiency of Aminoacylase-1 Enzyme

What is Aminoacylase 1 Deficiency Disorder? (Definition/Background Information)

• Aminoacylase 1 Deficiency (ACY1D) Disorder is an inborn error of metabolism marked by a characteristic pattern of urinary N-acetyl amino acid excretion and neurologic symptoms
• Most individuals with ACY1D Disorder identified so far are children who underwent selective screening tests for inborn errors of metabolism prompted mainly by delayed psychomotor development or by the occurrence of seizures. However, there is a considerable phenotypic variability between ACY1D individuals
• ACY1D is transmitted as an autosomal recessive trait

(Source: Neurological conditions associated with Aminoacylase 1 deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Who gets Aminoacylase 1 Deficiency Disorder? (Age and Sex Distribution)

• Aminoacylase 1 Deficiency Disorder is a rare congenital disorder, with less than 20 cases being reported in the medical literature. The exact prevalence of the disorder is not known
• The presentation of symptoms typically begins in childhood
• Both males and females may be affected
• Worldwide, individuals of all racial and ethnic groups may be affected

What are the Risk Factors for Aminoacylase 1 Deficiency Disorder? (Predisposing Factors)

• A positive family history may be an important risk factor, since Aminoacylase 1 Deficiency Disorder can be inherited
• Children of consanguineous parents may have an increased risk for this deficiency disorder

It is important to note that having a risk factor does not mean that one will get the condition. A risk factor increases one’s chances of getting a condition compared to an individual without the risk factors. Some risk factors are more important than others.

Also, not having a risk factor does not mean that an individual will not get the condition. It is always important to discuss the effect of risk factors with your healthcare provider.

What are the Causes of Aminoacylase 1 Deficiency Disorder? (Etiology)

Aminoacylase 1 Deficiency Disorder is caused by biallelic mutations in the ACY1 gene (3p21.2). It is transmitted as an autosomal recessive trait

• Aminoacylase 1 catalyzes the formation of free amino acids from N-acetylated precursors
• The enzyme is strongly expressed in the human brain and is a potential modifier affecting the severity or manifestation of different neurologic diseases

(Source: Neurological conditions associated with Aminoacylase 1 deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Autosomal recessive type of inheritance: Autosomal recessive conditions are traits or disorders that occur when two copies of an abnormal gene have been inherited on a non-sex chromosome. If both parents have an autosomal recessive condition, there is a 100% likelihood of passing on the mutated genes to their children. If, however, only one mutant copy of the gene is inherited, the individual will be a carrier of the condition, but will not be present with any symptoms. Children born to two carriers, have a 25% chance of being homozygous dominant (unaffected), a 50% chance of being heterozygous (carrier), and a 25% chance of being homozygous recessive (affected).

What are the Signs and Symptoms of Aminoacylase 1 Deficiency Disorder?

The signs and symptoms of Aminoacylase 1 Deficiency Disorder may vary among affected individuals, and include:

• Acute encephalopathy
• Cerebellar atrophy; cerebral atrophy
• Delayed CNS myelination
• Generalized hypotonia
• Global developmental delay
• Hyperactivity
• Hypertelorism
• Muscle weakness
• Seizures
• Sensorineural hearing impairment
• Wide nasal bridge

(Source: Aminoacylase 1 Deficiency Disorder; Genetic and Rare Diseases Information Center (GARD) of National Center for Advancing Translational Sciences (NCATS), USA.)

How is Aminoacylase 1 Deficiency Disorder Diagnosed?

• The diagnosis of Aminoacylase 1 Deficiency Disorder is made by gas chromatography-mass spectrometry (GC-MS) analysis of urinary organic acids revealing increased levels of N-acetylated amino acids, including methionine, glutamine, alanine, leucine, glycine, valine, and isoleucine derivatives, or by NMR spectroscopy of urine
• The diagnosis can be confirmed by identification of mutations in the ACY1 gene and by detection of reduced ACY1 enzyme activity in Epstein-Barr virus (EBV)-transformed lymphoblasts or in fibroblasts

(Source: Neurological conditions associated with Aminoacylase 1 deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Many clinical conditions may have similar signs and symptoms. Your healthcare provider may perform additional tests to rule out other clinical conditions to arrive at a definitive diagnosis.

What are the possible Complications of Aminoacylase 1 Deficiency Disorder?

The potential complications of Aminoacylase 1 Deficiency Disorder may include:

• Inability to walk
• Delay in speech development
• Risk of falls and injury due to seizures
• Intellectual disability
• Autism

Complications may occur with or without treatment, and in some cases, due to treatment also.

How is Aminoacylase 1 Deficiency Disorder Treated?

There is no cure for Aminoacylase 1 Deficiency Disorder, since it is a genetic condition. Treatment is usually given to manage the signs and symptoms and any complication that develops

How can Aminoacylase 1 Deficiency Disorder be Prevented?

Aminoacylase 1 Deficiency Disorder may not be preventable, since it is a genetic disorder.

• Genetic testing of the expecting parents (and related family members) and prenatal diagnosis (molecular testing of the fetus during pregnancy) may help in understanding the risks better during pregnancy
• If there is a family history of the condition, then genetic counseling will help assess risks, before planning for a child
• Active research is currently being performed to explore the possibilities for treatment and prevention of inherited and acquired genetic disorders
• Regular medical screening at periodic intervals with tests and physical examinations are recommended

What is the Prognosis of Aminoacylase 1 Deficiency Disorder? (Outcomes/Resolutions)

• Due to the small number of individuals known to have Aminoacylase 1 Deficiency Disorder and due to the young age of the reported patients, the clinical course cannot be fully predicted and the prognosis is unknown
• Characterization of additional patients and long-term follow-up are indicated

(Source: Neurological conditions associated with Aminoacylase 1 deficiency; Orphanet, National Institute of Health and Medical Research (INSERM), Paris.)

Additional and Relevant Useful Information for Aminoacylase 1 Deficiency Disorder:

The following DoveMed website link is a useful resource for additional information:

http://www.dovemed.com/diseases-conditions/rare-disorders/