Alström syndrome in a Chinese girl: a case report and literature review

Background: Alström syndrome (ALMS) is a rare autosomal recessive genetic disorder caused by homozygous or compound heterozygous mutations in the ALMS1 gene. The encoded ALMS1 protein is widely distributed, leading to the complex clinical manifestations of this disease. Currently, there are no effective curative treatments-disease-modifying or curative therapies.

Methods: Here, we report a case of ALMS in a Chinese female patient featuring nystagmus, visual impairment, diabetes mellitus, hepatosplenomegaly, mixed hearing loss, ovarian pedicle torsion, and acanthosis nigricans. Comprehensive clinical data—including anthropometric, laboratory, and imaging findings—were collected. Whole-exome sequencing identified biallelic pathogenic variants in the ALMS1 gene, confirming the diagnosis. For glycemic control, the patient was managed with a combination of insulin aspart, insulin detemir, and metformin.

Results: Whole-exome sequencing identified compound heterozygous mutations in the ALMS1 gene, leading to erroneous ALMS1 protein coding and confirming ALMS. The variant ALMS1 c.4839dupA was identified as a novel likely pathogenic mutation. Currently, there is no definitive treatment for this disease, and management primarily focuses on symptomatic support.

Conclusions: We identified a novel likely pathogenic variant in the ALMS1 gene as the underlying cause of ALMS in this Chinese patient. The clinical presentation highlights the remarkable phenotypic variability of the disorder, a key factor contributing to frequent diagnostic delays or errors. Consequently, early genetic confirmation is imperative to guide appropriate and timely interventions that can significantly improve patient care and quality of life.