Autopsy Findings in AGTPBP1 Gene-Related Infantile Neurodegeneration: A Case Report and Review of Literature

Homozygous mutations in the AGTPBP1 gene are associated with childhood-onset neurodegeneration and cerebellar atrophy (CONDCA). These mutations disrupt neuronal maintenance, leading to progressive motor and cognitive deficits. This case highlights the pathological findings and systemic complications in a 4.5-month-old boy with this rare genetic disorder.

A 4.5-month-old boy presented with global developmental delay and progressively worsening floppiness of the body for the past 2 months. There was a history of similar illness in his previous sibling, who died at 2.5 months of age. The serum creatine kinase of the index child was mildly elevated. Antemortem muscle biopsy had revealed the presence of neurogenic atrophy. Peripheral blood count revealed persistent lymphopenia (ALC range: 1,270/μL to 2,482/μL). The child developed severe respiratory distress and succumbed to his illness at 5 months of age. The autopsy revealed the atrophy of cerebellar folia with a striking reduction of Purkinje and granular cells and preserved molecular layer. There was thinning of the corpus callosum and anterior horn cell degeneration in the spinal cord. Lung examination demonstrated fibrinous bronchitis, bronchiolitis, and pneumonia; a result of adenovirus infection confirmed by electron microscopy and PCR. The thymus was absent. Genetic testing identified a homozygous mutation in the AGTPBP1 gene (c2833C>T), confirming the diagnosis of CONDCA.

This is the first autopsy description of CONDCA with detailed neuropathological evaluation. Although cerebellar atrophy is well known, this case reveals a wider neuropathological change and thymic aplasia in such patients. This case highlights the structural consequences of the AGTPBP1 gene-associated enzyme deficiency crucial for post-translational modifications of tubulin, resulting in the degeneration of specific sets of neurons and immune deficiency secondary thymic involvement.