Diagnosis and management of cystinosis: systematic review for a clinical practice guideline.

BACKGROUND

Cystinosis is a rare genetic disorder, with the majority of patients suffering from infantile nephropathic cystinosis, the most severe form. If left untreated, cystinosis causes serious morbidity, initially through progressive kidney and eye disease, followed by systemic and multiorgan involvement, ultimately leading to premature death. In this systematic review, we summarize the evidence for cystinosis to support the development of an evidence-based clinical practice guideline (SELECT - S3 guideline for cystinosis).

METHODS

We searched MEDLINE, Embase, CENTRAL, CINAHL, and other databases for relevant studies published from 1980 onward. We screened literature dually and independently for eligibility. Primary researchers extracted data, rated the risk of bias of included studies, and rated the certainty of the evidence (CoE). Secondary researchers reviewed for completeness and accuracy. We applied a staggered approach, prioritizing available controlled studies and synthesizing results narratively.

RESULTS

We considered 56 studies in our synthesis and assessed findings relevant to 17 of 31 key questions. We identified evidence for 62 of 213 outcomes. Fifty-two outcomes had very low CoE, three low, four moderate, and three high. The moderate and high CoE findings came from indirect comparisons (other chronic multi-organ diseases). There was low evidence that delayed-release cysteamine therapy makes little to no difference on cystine levels compared to immediate-release cysteamine therapy; however, delayed-release cysteamine was associated with a slight increase in adverse events. Starting systemic cysteamine treatment early likely improves renal function compared to a later start. Most included studies lacked a control group, had a high risk of bias, and had a small sample size.

CONCLUSION

Evidence informing the diagnosis and management of cystinosis is limited, with most findings rated as very low certainty. Few direct comparisons involving only individuals with cystinosis yielded low certainty findings, while moderate to high certainty evidence was found only in indirect comparisons. These findings underscore a critical challenge in managing cystinosis: the balancing act of clinical decision-making in the context of lacking evidence. Nonetheless, this systematic review synthesized the best available data for a clinical practice guideline and highlighted specific areas where future research could strengthen the evidence base.

SUPPLEMENTARY INFORMATION

The online version contains supplementary material available at 10.1186/s13023-025-03974-z.