Mitochondrial trifunctional protein deficiency caused by a deep intronic deletion leading to aberrant splicing.

Trifunctional protein deficiency (TFP) is a disorder of fatty acid beta-oxidation associated with metabolic, cardiac, and liver dysfunction in severe forms. We present two siblings diagnosed by newborn screening and confirmed by biochemical testing at birth. Their clinical course was complicated by recurrent rhabdomyolysis, retinopathy, and hypoparathyroidism.

Reactivation of mTOR signaling slows neurodegeneration in a lysosomal sphingolipid storage disease.

Sandhoff disease, a lysosomal storage disorder, is caused by pathogenic variants in the HEXB gene, resulting in the loss of β-hexosaminidase activity and accumulation of sphingolipids including GM2 ganglioside. This accumulation occurs primarily in neurons, and leads to progressive neurodegeneration through a largely unknown process. Lysosomal storage diseases often exhibit dysfunctional mTOR signaling, a pathway crucial for proper neuronal development and function.

Differential Tractography: A Biomarker for Neuronal Function in Neurodegenerative Disease.

GM1 gangliosidosis is an ultra-rare inherited neurodegenerative lysosomal storage disorder caused by biallelic mutations in the gene. GM1 is uniformly fatal and has no approved therapies, although clinical trials investigating gene therapy as a potential treatment for this condition are underway. Novel outcome measures or biomarkers demonstrating the longitudinal effects of GM1 and potential recovery due to therapeutic intervention are urgently needed to establish efficacy of potential therapeutics.