Anorexia as the first clinical manifestation of von Hippel-Lindau syndrome

Abstract

Hemangioblastomas (HBs) of the brain may present without neurological symptoms over a long period of time due to their benignity and slow growth. We herein present the case of a female patient who developed a HB of the fourth ventricle presenting only with severe weight loss and anorexia. The patient was screened for mutations in all 3 exons of the VHL gene using Sanger sequencing, and was found to have a nonsense mutation in the VHL gene (single-nucleotide change causing a premature stop codon: c.481C>T; p.Arg161*), causing formation of a truncated protein, consistent with von Hippel-Lindau syndrome (VHLs). The patient was first misdiagnosed with anorexia nervosa (AN) due to the lack of other symptoms. Molecular diagnosis allows further investigation of other VHLs-related tumors and timely, appropriate treatment. However, misdiagnosing anorexia nervosa may lead to poor prognosis and even death; thus, differential diagnosis is crucial in all such cases. The present case report provides evidence that fourth ventricular lesions may affect food intake control and satiety, and highlights the importance of accurate molecular diagnosis.

Keywords: VHL gene; anorexia; fourth ventricle; hemangioblastoma; von Hippel-Lindau syndrome.

Figure 1

Brain magnetic resonance imaging. (A) Solid and cystic expansive lesion formation within the inferior aspect of the fourth ventricle, extending inferiorly to the foramen magnum and superiorly to the cervical vertebral canal. (B and C) The lesion had a heterogeneous signal, facilitated the diffusion of water molecules, exhibited intense contrast enhancement, (D) signs of significant increase in relative blood flow and blood volume, was associated with adjacent ectatic vessels and posterior cranial fossa cisterns, and measured 6.1x3.2x3.0 cm (craniocaudally x laterolaterally x anteroposteriorly, respectively). (A) Fiesta T2-weighted sequence (sagittal view). (B and C) Gadolinium-enhanced T1-weighted sequence (axial and sagittal views). (D) perfusion-weighted sequence (axial view).

Figure 2

VHL sequencing. A missense mutation (c.481C>T) causing a premature stop codon (p.Arg161*) and a truncated VHL protein (black box, c.481 location; nucleotide C (blue line) was changed to T (red line) in heterozygosity. VHL, von Hippel-Lindau.