Alagille Syndrome Associated with Xerophthalmia
A 3-year-old boy was examined at our institution due to severe bilateral ocular-surface disease, more severe in the right eye. His medical history included neonatal cholestatic jaundice, which prompted us to make a thorough systemic evaluation. Liver biopsy revealed paucity of the intrahepatic bile ducts. Cardiac echography revealed a left-to-right shunt through an atrial septal defect and mild stenosis of the pulmonary arteries. Vertebral structure was normal on X-ray. The patient was first examined at our clinic at the age of 9 months, and a prominent posterior embryotoxon was noted bilaterally (fig. ). The combination of typical facial characteristics including a prominent forehead, bulbous nose and pointed chin together with systemic and ocular findings led to a clinical diagnosis of Alagille syndrome. His parents were reluctant to have genetic testing performed. During infancy, the main complaint was his failure to thrive, and a percutaneous endoscopic gastrostomy tube was inserted for added caloric supplementation along with the fat-soluble vitamins. The patient suffered from a significant developmental delay (e.g. he started walking only at the age of 2.5 years) and severe growth retardation under full caloric and pancreatic-enzyme supplementation (at the age of 3.5 years, he weighed 7.2 kg, which is below the 3rd percentile). He received chronic daily treatment with ursodeoxycholic acid and supplementation with the fat-soluble vitamins (AquADEKs, 1 ml until the age of 1 year, and then 2 ml; 1 ml contains vitamin A as 87% β-carotene and 13% palmitate, 5,751 IU which is 383% of the daily value for infants).\nSeveral months prior to examination at our clinic, he started complaining of severe bilateral ocular irritation. Because of constant eye-rubbing, it was assumed that he suffered from vernal keratoconjunctivitis, and he was treated with topical antihistamines. After failing to improve with this treatment, he was referred for our examination. At the initial evaluation, a central corneal ulcer was noted in the right eye, with marked opacity and central thinning of the cornea. The cornea in the left eye displayed mild opacities and diffuse superficial punctate keratitis. The fundus could not be seen in the right eye, but in the left eye, mild tilting and optic-disc pallor were noted as well as a few retinal pigmentary changes. A culture taken from the corneal ulcer in the right eye was positive for Staphylococcus mitis. The patient was treated with intensive topical cefamezine, garamycin and lubrication, and experienced a gradual improvement. Three weeks after his initial presentation to our clinic, the corneal infiltrate resolved, but a marked thinning remained. He underwent amniotic membrane transplantation with lower punctual occlusion (fig. ). Due to the clinical findings and his systemic condition, a suspicion of vitamin A deficiency was raised. This was confirmed by serum analysis of vitamin A, which measured 2 μg/dl; this is significantly lower than the normal range of 30–120 μg/dl. There were no Bitot's spots in either eye. It should be noted that, due to the patient's significant developmental delay, visual acuity could not be measured and he was unable to articulate any complaint regarding reduced vision or nyctalopia. The vitamin A supplementation was further increased and it resulted in a gradual improvement of the degree of ocular discomfort within the following months. The irritation had resolved, the patient was no longer rubbing his eyes, and the right cornea was adequately covered by conjunctival epithelium.