Infantile Systemic Hyalinosis: A Familiar Symptom Unveiling an Unusual Disease

Infantile systemic hyalinosis is a rare autosomal recessive disorder characterized by the widespread deposition of hyaline material in multiple organs leading to progressive multisystem involvement. Early clinical manifestations are often nonspecific and frequently result in diagnostic delay. We report a seven-month-old female infant born of a third-degree consanguineous marriage who presented with persistent watery diarrhea since early infancy with failure to thrive. Clinical examination showed coarse facial features, hyperpigmentation over joints, perianal rash, and markedly reduced joint mobility with preserved deep tendon reflexes. Laboratory evaluation showed anemia, neutrophilic leukocytosis, elevated inflammatory markers, hypoalbuminemia, and reduced immunoglobulin levels, while stool studies were non-contributory. Upper gastrointestinal endoscopy demonstrated scattered white mucosal lesions suggestive of lymphatic dilation or hyaline deposition. After the exclusion of infectious, metabolic, and malabsorptive causes, a genetic etiology was suspected. Whole exome sequencing identified a homozygous pathogenic frameshift mutation in the ANTXR2 gene (c.1074del; p.Ala359fs), confirming the diagnosis of infantile systemic hyalinosis. This case highlights the importance of considering rare genetic disorders in infants presenting with chronic diarrhea accompanied by joint contractures and skin lesions and emphasizes the role of early genetic testing for definitive diagnosis, appropriate counseling, and optimized supportive care.