History and Physical
A 10-year-old female with a history of developmental delay since the first year of life developed gait instability and nystagmus at the age of 3, followed by progressive motor and language regression. There was no relevant family or perinatal history.
Neurologic examination revealed horizontal nystagmus, axial hypotonia, dysmetria, and tremor of the upper limbs. Additionally, there was spastic quadriparesis with pyramidal signs. The patient had a visual connection with the environment but lacked verbal language.
Diagnostic Workup
Laboratory testing for ceruloplasmin, copper, alpha-fetoprotein, cholesterol, vitamin levels, and albumin were all within normal ranges. Intermediary metabolism studies showed no significant alterations. Laboratory evaluation, including lipofuscinosis and congenital disorders of glycosylation, was unremarkable.
Genetic consultation was requested. Karyotype was normal 46, XX. DNA methylation and genetic testing for Friedrich ataxia and Fragile X syndrome were negative. Electromyography and nerve conduction studies showed axonal compromise of the sciatic and popliteal nerves.
Serial brain MRI between 2 and 5 years of age demonstrated progressive cerebellar atrophy ( Figs. 69.1 and 69.2 ). By 10 years of age, cerebral atrophy had also developed, with excessive mineralization in the bilateral globus pallidus and substantia nigra ( Fig. 69.3 ). Targeted genetic testing revealed a pathogenic variant in the Phospholipase A 2 -group VI ( PLA2G6 ) gene.
PLA2G6 -associated neurodegeneration. Brain MRI at 2 years of age. Axial T2 with fat suppression shows (A) cerebellar atrophy and (B and C) mild hypointense mineralization of substantia nigra and globus pallidus.
PLA2G6 -associated neurodegeneration. Brain MRI at 5 years. (A) Axial T2 and (B) sagittal postcontrast T1 show progression of cerebellar atrophy (circle).
