Ketogenic diet improves renal Fanconi syndrome in nephropathic cystinosis: first human proof-of-principle from an n-of-1 pediatric study

Cystinosis is a rare inherited metabolic disorder caused by pathogenic variants in the CTNS gene and characterized by progressive lysosomal cystine accumulation in virtually all organs and tissues. Clinically, the disease presents with renal Fanconi syndrome (RFS) during the first year of life and, if left untreated, progresses to end-stage kidney disease around the age of 10 years. In addition to renal involvement, cystinosis affects multiple extra-renal organs, including the eyes, thyroid gland, muscles, brain, pancreas, and gonads. Treatment with the cystine-depleting agent cysteamine delays disease progression. In two rodent models of cystinosis (mouse and rat), a ketogenic diet (KD) has recently been shown to markedly improve features of RFS and chronic kidney injury. Inspired by these findings, we initiated KD treatment in a 7-year-old boy with cystinosis and RFS. The diet was administered via a gastrostomy tube for six months. Following an initial adaptation period, the intervention was well tolerated. After three and six months of treatment, we observed substantial improvements in proximal tubular reabsorption and growth. In addition, KD treatment was associated with improvements in several patient-reported outcome measures. In conclusion, this single-case observation provides preliminary clinical evidence supporting the translational potential of ketogenic dietary therapy in cystinosis. These findings strengthen the rationale for prospective clinical studies to evaluate the safety, feasibility, and efficacy of KD in a larger cohort of patients with cystinosis.