Classification and differential diagnosis of Wilson’s disease

Abstract

Wilson's disease is characterized by hepatic and extrapyramidal movement disorders (EPS) with variable manifestation primarily between age 5 and 45. This variability often makes an early diagnosis difficult. A classification defines different clinical variants of Wilson's disease, which enables classifying the current clinical findings and making an early tentative diagnosis. Until the unequivocal proof or an autosomal recessive disorder of the hepatic copper transporter ATP7B has been ruled out, differential diagnoses have to be examined. Laboratory-chemical parameters of copper metabolism can both be deviations from the norm not related to the disease as well as other copper metabolism disorders besides Wilson's disease. In addition to known diseases such as Menkes disease, occipital horn syndrome (OHS), Indian childhood cirrhosis (ICC) and ceruloplasmin deficiency, recently discovered disorders are taken into account. These include MEDNIK syndrome, Huppke-Brendel syndrome and CCS chaperone deficiency. Another main focus is on differential diagnoses of childhood icterus correlated with age and anaemia as well as disorders of the extrapyramidal motor system. The Kayser-Fleischer ring (KFR) is qualified as classical ophthalmologic manifestation. The recently described manganese storage disease presents another rare metabolic disorder with symptoms similar to Wilson's disease. As this overview shows, Wilson's disease fits into a broad spectrum of internal and neurological disease patterns with icterus, anaemia and EPS.

The Patient-Reported Experience of Living with Wilson Disease

“…The resulting inability to regulate Cu levels leads to the accumulation of toxic amounts of Cu in patients with Wilson disease, which causes liver damage and neurological signs and symptoms [4]. Prevalence is estimated to be 1 in 30,000 people, but this is likely an underestimate since many cases go undiagnosed and there are no recent population-based epidemiological studies with updated prevalence estimates [1,5,6]. Recent molecular studies also indicate a potential greater prevalence [6].…”

Wilson’s Disease: Diagnosis of Wilson’s Disease in Ethiopian Young Sisters

“…Bilateral hyperintensities in basal ganglia is spotted in T1-weighted MRI imaging. Genetic testing for SLC30A10 gene mutation settles the diagnosis [ 8 ].…”

“…Axial T 2 -weighted and FLAIR-MRI images suggest bilateral hyperintensities on basal ganglia, brain stem, and cerebellum. "Face of the giant panda" in the midbrain is classic MRI sign [2][3][4][5][6][7][8][9][10][11]. Diagnosis of Wilson's disease is established by the scoring system proposed by "8 th International Meeting on Wilson Disease and Menkes Disease, Leipzig (2001)," which encompasses the combination of clinical signs, biochemical parameters, histologic findings, and mutation analysis of ATP7B gene [6].…”

Laser Ablation Inductively Coupled Plasma Spectrometry: Metal Imaging in Experimental and Clinical Wilson Disease

“…In sum, diagnosis and classification of Cu overload occurring in WD, and its discrimination from other related metal metabolism or storage diseases, requires a high index of suspicion and is based on a combination of clinical signs, biochemical tests, measurements on hepatic Cu, and mutation analysis [21,23].…”