Leukodystrophy in Tanzania: A Case Study Highlighting Diagnostic Dilemmas and Clinical Implications

Abstract

ABSTRACT Leukodystrophies are rare inherited neurodegenerative disorders characterized by progressive white matter dysfunction and neurological decline. In low‐resource settings, limited access to advanced neuroimaging, biochemical investigations, and genetic testing often delays diagnosis and complicates differentiation from more common infectious, nutritional, and hematological conditions. We describe a 16‐month‐old boy who presented with lower limb weakness, irritability, feeding difficulties, and skin abnormalities during an acute respiratory infection. Initial evaluation raised differential diagnoses including tuberculosis, lymphoma, and leukemia because of overlapping clinical and laboratory features. Neuroimaging demonstrated bilateral periventricular white matter abnormalities and frontotemporal atrophy suggestive of leukodystrophy, with the clinical and radiologic presentation being compatible with suspected metachromatic leukodystrophy (MLD). Subsequent exome sequencing identified a variant in the fructose‐1,6‐bisphosphatase 2 (FBP2) gene associated with childhood‐onset leukodystrophy. However, definitive biochemical and molecular confirmation for MLD, including ARSA enzyme activity, urinary sulfatide analysis, and ARSA/PSAP sequencing, was not available. The patient showed partial clinical improvement following supportive management, including treatment for intercurrent infection and vitamin D deficiency. This case highlights the diagnostic challenges of suspected leukodystrophies in under‐resourced environments, where clinical suspicion often exceeds available diagnostic capacity. Furthermore, it underscores the global disparity in access to specialized metabolic and genetic testing, emphasizing the need for improved multidisciplinary collaboration and expanded diagnostic infrastructure to support timely diagnosis, counseling, and management of rare neurological disorders.