aminoacylase 1 deficiency

Aminoacylase 1 deficiency is an inherited metabolic condition that primarily affects the brain and other body systems. It results from pathogenic variants in the ACY1 gene, which provides instructions for an enzyme that normally breaks down N-acetylated amino acids. Symptoms usually begin in infancy or early childhood and include neurological and developmental concerns such as seizures and low muscle tone. Fewer than one in a million people are thought to be affected worldwide, making it an exceptionally rare diagnosis. Because awareness and testing have improved over time, additional individuals are now being identified earlier in life.

The condition is first suspected when newborns or infants show feeding difficulties, generalized hypotonia, and episodes of acute encephalopathy or seizures. Neurological features dominate the clinical picture, and many children experience global developmental delay that can affect cognitive and motor skills. Imaging studies often reveal cerebral cortical atrophy, and some individuals have structural brain changes such as a thin corpus callosum or small cerebellar vermis. Cardiovascular signs like bradycardia, breathing problems including apnea, or gastrointestinal symptoms such as vomiting may accompany the neurological findings. Not all individuals experience all features, and severity varies considerably, with some children having milder muscle weakness while others face recurrent tonic-clonic seizures.

Aminoacylase 1 deficiency is caused by alterations in the ACY1 gene. The ACY1 enzyme normally removes acetyl groups from specific amino acids so they can be reused or broken down; when the enzyme is absent or not working properly, N-acetyl amino acids accumulate and likely contribute to neurological dysfunction. The condition is inherited in an autosomal recessive pattern, meaning a child must receive one altered ACY1 gene from each parent to be affected. Parents who share a common ancestor are more likely to carry the same rare variant, so the condition can be more common in related families. Carrier parents usually have no symptoms but have a 25 percent chance with each pregnancy of having an affected child. Genetic counseling can help families understand carrier testing, reproductive options, and implications for other relatives.

Currently, management focuses on supportive care and symptom control. Seizure management under a neurologist, nutritional support for feeding difficulties, and physical or occupational therapy to address hypotonia are typical components of care. Because multiple organ systems can be involved, a multidisciplinary team that may include neurology, gastroenterology, cardiology, nutrition, and developmental specialists is recommended. Regular surveillance for emerging complications, such as monitoring growth, neurological status, and respiratory function, helps clinicians intervene early and adjust therapies as a child’s needs change. Families are encouraged to discuss individualized treatment plans and emerging research with their healthcare team.

Long-term outcomes vary widely between individuals. Some children achieve meaningful developmental progress with early intervention, while others experience persistent neurological challenges that require ongoing support. Complications such as uncontrolled seizures or severe feeding problems can affect overall health, but proactive management often improves quality of life. Outcomes described in medical literature continue to evolve as standards of care improve. Families often find it helpful to connect with genetic counselors and specialists familiar with metabolic and developmental disorders, and support groups can provide practical advice and emotional connection.