Angelman syndrome and isovaleric acidemia: What is the link?

Area of Science:

• Genetics
• Metabolic Disorders
• Neurodevelopmental Disorders

Background:

• Angelman syndrome is a genetic disorder affecting neurodevelopment.
• Isovaleric acidemia (IVA) is an inborn error of metabolism that can impact neurodevelopment.
• Paternal uniparental isodisomy of chromosome 15 (UPD 15) is a rare genetic phenomenon.

Purpose of the Study:

• To report a case of Angelman syndrome co-occurring with isovaleric acidemia (IVA).
• To investigate the genetic basis of this rare association.
• To discuss the implications for managing IVA in patients with Angelman syndrome.

Main Methods:

• Case report of a toddler with Angelman syndrome and IVA.
• Genetic analysis to determine the underlying cause of the co-occurrence.
• Review of the literature regarding paternal UPD 15 and co-occurring conditions.

Main Results:

• The co-occurrence was attributed to paternal UPD 15, where the patient inherited two copies of an IVA gene mutation from the father.
• The identified IVA gene variant was likely asymptomatic in this patient, leading to mild organic aciduria.
• This case demonstrates a rare instance of Angelman syndrome associated with a potentially treatable inborn error of metabolism.

Conclusions:

• Paternal UPD 15 can rarely lead to the simultaneous occurrence of Angelman syndrome and inborn errors of metabolism.
• Even when a metabolic disorder appears asymptomatic, its potential impact on neurodevelopment warrants consideration.
• This case underscores the importance of comprehensive genetic evaluation and metabolic screening in individuals with Angelman syndrome.