Hepatolenticular degeneration-induced hepatic dysfunction with extremely atypical clinical manifestations: a Case Report

Abstract

Hepatolenticular Degeneration (HLD) is a rare condition caused by a genetic copper metabolism disorder and a basal ganglia-dominated degenerative brain disease. Its characteristic clinical features include progressive extrapyramidal symptoms, psychiatric manifestations, cirrhosis, renal impairment, and the Kayser-Fleischer ring. Furthermore, its key diagnostic bases include the ceruloplasmin level, copper oxidase activity, trace copper in the human body, brain Magnetic Resonance Imaging (MRI), and genetic testing. Here, we present an HLD case with atypical clinical manifestations. A 43-year-old male HLD patient presented to our hospital with normal copper oxidase activity and serum copper levels, as well as results of ceruloplasmin testing, slit-lamp examination, and histopathological examination of the liver, which showed no typical manifestations. On the other hand, the genetic testing results showed new mutation sites. To improve our clinical understanding of HLD and reduce the probability of misdiagnosis and missed diagnosis, we discussed and clarified the clinical manifestations, pathogenesis, and diagnosis and treatment of the disease, all based on existing literature.

Keywords: atypical clinical manifestations; case report; hepatic dysfunction; hepatolenticular degeneration; whole exome sequencing.

Figure 1

Key findings of patient at critical time points. ALT, alanine aminotransferase; AST, aspartate aminotransferase; AFP, alpha-fetoprotein; MR, magnetic resonance; HBV, hepatitis B virus serological markers; AIH, autoimmune hepatitis; CTD, connective tissue diseases; CEA, carcinoembryonic antigen; CA19-9, carbohydrate antigen 19-9; CER, ceruloplasmin; WES, whole exome sequencing; LSM, liver stiffness measurement. The figure shows key findings at patient's critical time points.

Figure 2

Brain MRI, liver ultrasonography and corneal K-F ring examination. (A–C) T1, T2, and Flair high signal in the left lentiform nucleus on the brain MRI plain scan; (D–F) Multiple speckled T1WI or slightly lower T2WI high signal shadows, with a high signal on FLAIR in the bilateral cerebral cortex on brain MRI plain scan; (G) Multiple hyperechoic nodules scattered in the liver; and (H, I) Few corneal K-F rings observed during slit-lamp examination.

Figure 3

Monitoring charts for the serum ceruloplasmin level and liver function indexes. (A) Serum ceruloplasmin level monitoring chart; (B) Alanine aminotransferase monitoring chart; (C) Aspartate aminotransferase monitoring chart. Serum ceruloplasmin levels of the patient were slightly low or normal. After diagnosed with HLD in June 19, 2023 and received treatment with copper chelation and liver protection drugs, the patient showed improvement in the liver function indicators between September 25, 2023 and November 29, 2023.

Figure 4

Pathological examination of liver. (A) Hematoxylin-Eosin staining, with turbid and swollen liver cells, visible focal necrosis, mild mixed liver steatosis; (B) Masson's Trichrome staining (+); (C) Reticular Fiber staining (+); (D) Periodic Acid-Schiff staining (+); (E) Copper staining (−); (F) Iron staining (−).