PA29 A rare case of infantile systemic hyalinosis due to <i>ANTXR2</i> gene mutation

Abstract Infantile systemic hyalinosis (ISH) is a rare but fatal autosomal recessive multisystem disease under the umbrella of hyaline fibromatoses syndromes. It is characterized by multiorgan deposition of hyaline secondary to a dysfunctional anthrax toxin receptor 2 gene (ANTXR2). ISH presents with a range of diagnostically challenging clinical features including skin lesions, joint contractures and systemic complications. We present the case of an 8-month-old girl who endured a rapid, terminal progression of the condition, where the pathognomonic cutaneous signs served to be pivotal in early diagnosis, highlighting the role of multidisciplinary input to ensure quality patient care, in the absence of established curative or definitive treatments. Our patient, of Middle Eastern descent, was born at 36 + 1 weeks’ gestation via spontaneous vaginal delivery to consanguineous parents in an otherwise unremarkable pregnancy. She had low birth centiles (25–50) and was noted to have an unexplained right-sided Erb’s palsy in early infancy. This evolved into paucity of movements from the painful contracture stiffness, affecting the large joints of the upper and lower limbs bilaterally. The stiffness progressively worsened into severe physical disability and chronic debilitating pain, refractory to rehabilitative physiotherapy. She also demonstrated feeding difficulties alongside persistent diarrhoea, which was unresponsive to supportive nutritional and dietetic intervention, gradually declining into 2–9% growth centiles. At 3 months of age, she developed abnormal skin turgor. Further dermatological assessment showed dependent, puffy oedema in her extremities, and macular hyperpigmentation over bony prominences of her bilateral medial malleoli and meta­carpophalangeal joints of her hands. Skin biopsy revealed normal histology; however, genetic testing revealed a homozygous pathogenic missense mutation in the ANTXR2 gene. By 6 months of age, she struggled to thrive due to multisystemic failures including protein-losing enteropathy, pancreatic exocrine failure and collateral immune compromise. A multidisciplinary decision was made for palliative care with supportive intravenous fluid resuscitation, antimicrobial therapy, pain relief and nutritional support. However, while in hospice, she succumbed to urosepsis at 8 months of age. This case illustrates the awareness of the dermatological manifestations of ISH to aid diagnosis. Given the scarcity of cases reported in the current literature and the multisystem manifestations with a poor outcome, a multidisciplinary approach towards recognizing and holistically managing these cases is critical.