The Importance of Clinical Findings in the Evaluation of Genetic Testing A Pseudo-Gaucher

Gaucher disease is an autosomal recessive lysosomal storage disorder resulting from reduced or absent glucocerebrosidase enzyme activity due to pathogenic mutations in the GBA gene. The disease is classified into three main forms: Type 1 (non-neuropathic), Type 2 (acute neuropathic), and Type 3 (subacute neuropathic). Type 1 is the most prevalent form of the disease and is characterised by clinical features such as hepatosplenomegaly, anemia, bone pain, and growth retardation. In this case report, we present the genetic evaluation of a 10-year-old male patient with bilateral knee and Achilles tendon pain accompanied by intermittent numbness in the hands, as well as his family members is presented. Given the presence of previously diagnosed Gaucher patients within the family, a genetic analysis was performed with a preliminary diagnosis of Gaucher disease. Two previously reported pathogenic mutations in the GBA gene were identified, and comparison of familial genetic data revealed that these mutations were located in cis configuration, indicating that the index case was a carrier, not an affected individual. The findings point to a rare mutational combination of N409S and V499M occurring in cis, which may represent a population-specific pattern in Turkey. This study highlights the critical importance of interpreting genetic testing results in conjunction with clinical and biochemical findings for the accurate diagnosis of genetic disorders.