AUTHOR=Kirk Frederik Teicher , Munk Ditte Emilie , Ek Jakob , Birk Møller Lisbeth , Bendixen Thorup Mette , Hvid Danielsen Erik , Vilstrup Hendrik , Ott Peter , Damgaard Sandahl Thomas TITLE=Case report: Huppke–Brendel syndrome in an adult, mistaken for and treated as Wilson disease for 25 years JOURNAL=Frontiers in Neurology VOLUME=13 YEAR=2022 URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2022.957794 DOI=10.3389/fneur.2022.957794 ISSN=1664-2295 ABSTRACT=Background

Huppke–Brendel (HB) syndrome is an autosomal recessive disease caused by variants in the SLC33A1 gene. Since 2012, less than ten patients have been reported, none survived year six. With neurologic involvement and ceruloplasmin deficiency, it may mimic Wilson disease (WD).

Objectives and methods

We report the first adult patient with HB.

Results

The patient suffered from moderate intellectual disability, partial hearing loss, spastic ataxia, hypotonia, and unilateral tremor of parkinsonian type. At age 29, she was diagnosed with WD based on neurology, elevated 24H urinary copper, low ceruloplasmin, and pathological 65Cu test. Approximately 25 years later, genetic testing did not support WD or aceruloplasminemia. Full genome sequencing revealed two likely pathogenic variants in SLC33A1 which combined with re-evaluation of neurologic symptoms and MRI suggested the diagnosis of HB.

Conclusion

Adult patients with HB exist and may be confused with WD. Low ceruloplasmin and the absence of ATP7B variants should raise suspicion.