Pearls & Oy-sters: Challenges and Controversies in Wilson Disease

Abstract

Wilson disease (WD) is a genetic disorder of copper metabolism caused by variants in the ATP7B gene, which are inherited in an autosomal recessive pattern. Despite all the advances made on pathogenesis, cellular biology, and genetics, to date, WD remains a diagnostic and therapeutic challenge. With this series of cases, we aim to illustrate the main challenges that clinicians may encounter when dealing with patients with WD: the difficulties with clinical diagnosis, the therapeutic management of WD and the indication for advanced therapies, management during pregnancy, and genotype-phenotype correlations.

Figure 1. Ophthalmologic, Radiologic, and Pathologic Findings In Our Cases

(A) Brain MRI images from case 1. Pontine hypointensities are observed in T1 sequences and hyperintensities in midbrain, pontine nucleus, tegmentum, and periaqueductal gray matter (arrows in the upper left of the figure) in fluid-attenuated inversion recovery-T2 sequences, suggesting the diagnosis of central pontine myelinolysis. It is also shown that the hyperintensity of the midbrain contrasts with the hypointensity of the red nucleus, the pars reticularis of the substantia nigra, and the aquaductus (arrows), which are relatively spared, resembling the face of a panda. Bilateral lenticular hypointensities can also be seen (arrows in the upper right of the figure). (B) Pathologic findings are shown (hematoxylin and eosin stain), both (B.a) macroscopically and (B.b–B.d) microscopically, showing central pontine vacuolization and loss of glial cells. Both findings are consistent with central pontine myelinolisis. (B.b–B.d) Vacuolization is marked with arrowheads and a star in microscopic samples. (C) Kayser-Fleischer ring is marked with an arrow.

Figure 2. Images of a Baby Boy Born to One of the Sisters From Case 3

Penicillamine-induced cutis laxa syndrome in a baby boy born to a mother on d-penicillamine during pregnancy (case 3). The wrinkled appearance of baby's skin can be seen, which is particularly evident in his forehead, lips, neck, and fold areas, such as underarms and groins.