The first Vietnamese patient who presented late onset of pantothenate kinase-associated neurodegeneration diagnosed by whole exome sequencing: A case report

Abstract

Rationale: Pantothenate kinase-associated neurodegeneration (PKAN), also called Hallervorden-Spatz syndrome, is a rare autosomal recessive disease associated with brain iron accumulation and characterized by progressive dystonia, dementia, and dysarthria symptoms. PKAN, caused by a defective pantothenate kinase 2 (PANK2) gene, is the most common neurodegeneration with a brain iron accumulation (NBIA) group. The "eye of the tiger" sign in the magnetic resonance imaging demonstrated a bilateral hyperintense signal in the basal ganglia region on T2-weighted images, which is a characteristic feature of the diagnosis. PKAN is classified into 2 main types. The early-onset type (classic type) with rapid progression is characterized by symptoms of gait impairment and dystonia leading to loss of ambulation in early childhood. In the later-onset type (atypical type), slow progression usually takes place in the second decade of life with symptoms of neurodegeneration, dystonia, dysarthria, rigidity, choreoathetosis, and motor impairment. Until now, PKAN patients have only been reported in a few countries in Asia such as China, Korea, India, Iran, Taiwan, and Thailand.

Patient concerns: Here we report the first case of PKAN in Vietnam. The patient had a late onset but the disease progresses rapidly with symptoms of dyskinesia, dysphagia, and difficulty speaking.

Diagnoses: Pantothenate kinase-associated neurodegeneration.

Interventions: Whole exome sequencing was performed to identify heterozygous mutations in the PANK2 gene (NM_153638.4) (c.856C>T, p.Arg286Cys and c.1351C>T, p.Arg451Ter) that has been confirmed as the cause of the disease.

Outcomes: In this study, the first Vietnamese patient with late-onset PKAN was diagnosed by the whole exome sequencing method.

Lessons: The patient's case marks an important milestone for the first case in Vietnam. The results of the study will provide a scientific basis for clinicians in the diagnosis and genetic counseling of patients.

Figure 1.

T2 weighted MR imaging in the patient with the “eye of the tiger” sign, which is a characteristic feature of pantothenate kinase-associated neurodegeneration, showed an area of marked hypointensity in the globus pallidus.

Figure 2.

(A) Pedigree and the Sanger sequencing results of the members of the patient’s family. The results show that a heterozygous mutation (c.856C > T, p.Arg286Cys) in the PANK2 gene is detected in the patient and his father, and another heterozygous mutation (c.1351C > T, p.Arg451Ter) is found in the patient, his mother, and his older brother. (B) Position of the mutations in the structure model of the PANK2 protein. PANK2 = pantothenate kinase 2.