A Clinical Neurological Approach to the Child With Adenosine Deaminase Deficiency

Area of Science:

• Pediatric Neurology
• Immunology
• Biochemistry

Background:

• Severe combined immunodeficiency (SCID) due to adenosine deaminase (ADA) deficiency is a rare genetic disorder.
• ADA deficiency leads to toxic substrate accumulation in tissues, notably the brain, causing neurological symptoms.
• Neurological manifestations include seizures, developmental disorders, hypotonia, and sensorineural hearing loss, which are not reversed by hematopoietic stem cell transplantation.

Purpose of the Study:

• To characterize the neurological complications in children with ADA deficiency SCID.
• To propose an efficient neurological assessment protocol using electrophysiological, radiological, and neurocognitive studies.

Main Methods:

• A descriptive, observational study (retrospective and prospective) was conducted.
• Patients with confirmed ADA deficiency SCID were evaluated between 1996 and 2021.
• Neurological assessments included clinical evaluation, neuroimaging, and electrophysiological studies.

Main Results:

• Ten patients with ADA deficiency SCID were analyzed.
• All patients exhibited neurodevelopmental delay; common findings included hypotonia (6/10), sensorineural hearing loss (4/10), and language delay (3/10).
• Neuroimaging revealed brain calcifications (4/10) and enlarged subarachnoid spaces (2/10); epilepsy developed in two patients.

Conclusions:

• Neurological involvement and neuroimaging abnormalities are frequent in pediatric ADA deficiency SCID.
• Central nervous system substrate accumulation is a likely cause, but chronic infections must be excluded.
• Pediatric neurologists should be integral to the multidisciplinary care of these patients.