A Case Report: Diagnostic Route of a Patient with PLA2G6-Infantile Neuroaxonal Dystrophy and Familial Hyperlipidemia

The PLA2G6 gene, located on chromosome 22, is responsible for the synthesis of phospholipase A2, an enzyme that breaks down the fatty acyl groups of phospholipids. As a result of pathogenic variants of the gene, enzyme activity is impaired and oxidative damage occurs in phospholipid membranes.

A 17-month-old girl presenting with complaints of delayed walking and hearing loss was evaluated for inherited metabolic disorders. Metabolic screening revealed elevated levels of C22 and C24 in the very long-chain fatty acids (VLCFAs) analysis. First of all, PEX gene testing and then whole exome sequencing (WES) did not reveal any peroxisomal or inherited metabolic disorders; however, a heterozygous pathogenic variant was identified in the LDLR gene, which may explain the patient's elevated cholesterol levels. The patient's brain magnetic resonance imaging revealed bilateral posterior periventricular deep white matter hyperintensities, with subsequent development of cerebellar atrophy. Whole genome sequencing analysis identified a pathogenic homozygous variant in the deep intronic region of the PLA2G6 (NM_003560.4: c.2035-926G>A) gene according to the ACMG 2015 criteria. Our patient was diagnosed with PLA2G6-infantile neuroaxonal dystrophy.

Hyperlipidemia is a common finding, and it can cause misleading elevations in VLCFAs. This case report highlights the importance of detailed genetic analysis in the diagnosis of such cases.