Infantile neuroaxonal dystrophy (INAD) is a rare neurodegenerative disease. Two boys aged 3 years and 4 years and 2 months respectively, were admitted to the hospital due to delayed mental and motor development. There were no abnormalities at birth, and both children had low muscle strength and tension on admission. One child was not able to stand alone and had impaired vision. Electromyography showed neurogenic damage, and head MRI revealed cerebellar atrophy. High-throughput sequencing revealed compound heterozygous mutations in the PLA2G6 gene in the two children. The mutations (IVS11-1G>T and c.1984C>G) in one child were new mutations, and immunohistochemistry showed a reduction in the protein expression of PLAG6 in the muscular tissue of this child. INAD has the main clinical manifestations of psychomotor developmental regression and cerebellar atrophy. High-throughput sequencing can help with clinical diagnosis.
Child, Preschool ; Group VI Phospholipases A2 ; genetics ; Humans ; Magnetic Resonance Imaging ; Male ; Mutation ; Neuroaxonal Dystrophies ; genetics ; Neurodegenerative Diseases ; genetics

Carrier Proteins ; genetics ; Evoked Potentials, Auditory, Brain Stem ; Humans ; Infant ; Iron Metabolism Disorders ; genetics ; physiopathology ; Male ; Mutation ; Neuroaxonal Dystrophies ; genetics ; physiopathology ; Spasms, Infantile ; genetics ; physiopathology

Pantothenate kinase-associated neurodegeneration (PKAN) is a neurodegenerative disorder characterized by iron accumulation in the globus pallidus (GP) of the brain (neurodegeneration with brain iron accumulation [NBIA]), which is characterized by dystonia and spasticity resulting in postural difficulties. A 33-month-old boy was admitted with a pronounced gait disturbance. Marked hypertonicity in the patient's both calf muscles was noted, resulting in waddling with repeated slip-falls. NBIA was suspected by high T2 intensity in the GP on brain MRI, then it was confirmed by detecting PANK2 mutation. Botulinum toxin-A injection was administered to both calf muscles. After 2 weeks, a decrease in spasticity and an increase in range of motion were observed, and consequently, an increase in the patient's gait stability with both heels touching the ground, enabling him to walk straight independently. A definitive treatment for NBIA has not been established, and a symptomatic therapy is currently the mainstay of treatment in this case. This is the first case report of botulinum toxin injection for treatment of gait disturbance caused by spasticity in an infantile-onset PKAN.
Botulinum Toxins ; Brain* ; Child, Preschool ; Dystonia ; Gait ; Globus Pallidus ; Heel ; Humans ; Iron* ; Magnetic Resonance Imaging ; Male ; Muscle Spasticity* ; Muscles ; Neurodegenerative Diseases ; Pantothenate Kinase-Associated Neurodegeneration ; Range of Motion, Articular

OBJECTIVETo investigate the clinical symptoms and potential mutations in the PLA2G6 gene for a child with infantile neuroaxonal dystrophy.

METHODSClinical data of the patient was collected. The coding regions of PLA2G6 gene was subjected to Sanger sequencing using blood DNA from the patient and her parents.

RESULTSThe patient has presented with psychomotor regression and hypotonia, followed by development of tetraparesis. A novel homozygous mutation G68A in the PLA2G6 gene was found by DNA sequencing, while her parents were both heterozygous carriers.

CONCLUSIONThe psychomotor regression and tetraparesis of the patient was caused by infantile neuroaxonal dystrophy due to a novel homozygous mutation in the PLA2G6 gene, which was inherited from her parents.

Adult ; Base Sequence ; Brain ; diagnostic imaging ; Child, Preschool ; DNA Mutational Analysis ; Female ; Group VI Phospholipases A2 ; genetics ; Homozygote ; Humans ; Magnetic Resonance Imaging ; Male ; Molecular Sequence Data ; Mutation ; Neuroaxonal Dystrophies ; diagnostic imaging ; genetics ; Radiography

OBJECTIVE: Neurodegeneration with brain iron accumulation (NBIA) represents a group of inherited movement disorders characterized by iron accumulation in the basal ganglia. Recent advances have included the identification of new causative genes and highlighted the wide phenotypic variation between and within the specific NBIA subtypes. This study aimed to investigate the current status of NBIA in Korea. METHODS: We collected genetically confirmed NBIA patients from twelve nationwide referral hospitals and from a review of the literature. We conducted a study to describe the phenotypic and genotypic characteristics of Korean adults with atypical pantothenate kinase-associated neurodegeneration (PKAN). RESULTS: Four subtypes of NBIA including PKAN (n = 30), PLA2G6-related neurodegeneration (n = 2), beta-propeller protein-associated neurodegeneration (n = 1), and aceruloplasminemia (n = 1) have been identified in the Korean population. The clinical features of fifteen adults with atypical PKAN included early focal limb dystonia, parkinsonism-predominant feature, oromandibular dystonia, and isolated freezing of gait (FOG). Patients with a higher age of onset tended to present with parkinsonism and FOG. The p.R440P and p.D378G mutations are two major mutations that represent approximately 50% of the mutated alleles. Although there were no specific genotype-phenotype correlations, most patients carrying the p.D378G mutation had a late-onset, atypical form of PKAN. CONCLUSIONS: We found considerable phenotypic heterogeneity in Korean adults with atypical PKAN. The age of onset may influence the presentation of extrapyramidal symptoms.
Adult ; Age of Onset ; Alleles ; Basal Ganglia ; Brain ; Dystonia ; Freezing ; Gait ; Gene Frequency ; Genetic Association Studies ; Humans ; Iron ; Korea ; Movement Disorders ; Neurodegenerative Diseases ; Pantothenate Kinase-Associated Neurodegeneration* ; Parkinsonian Disorders ; Phenotype ; Population Characteristics* ; Referral and Consultation ; Weather

PURPOSE: Pantothenate kinase-associated neurodegeneration (PKAN), also known as neurodegeneration with brain iron accumulation is an extremely rare degenerative disease. The present study reports a case of retinal pigmentary changes in PKAN. CASE SUMMARY: A 6-year-old girl presented with night blindness and developmental delay. Neurologic examination revealed toe gait and dystonia. Ocular examination showed retinal pigmentary change in the entire retina without optic atrophy. Brain magnetic resonance imaging showed iron deposits in the basal ganglia, the so-called "eye of the tiger" sign. Genetic tests confirmed a mutation in the gene encoding pantothenate kinase 2. Electroretinography demonstrated severe loss of rod and cone responses, prominently reduced in the rod response. The patient was diagnosed with PKAN and pharmacologic treatment started. CONCLUSIONS: In the case of systemic neurological abnormalities with pigmentary retinal change, PKAN should be considered as a differential diagnosis.
Basal Ganglia ; Brain ; Diagnosis, Differential ; Dystonia ; Electroretinography ; Gait ; Humans ; Iron ; Magnetic Resonance Imaging ; Neurologic Examination ; Night Blindness ; Optic Atrophy ; Pantothenate Kinase-Associated Neurodegeneration ; Phosphotransferases ; Phosphotransferases (Alcohol Group Acceptor) ; Retina ; Retinal Degeneration ; Retinaldehyde ; Toes

Hallervorden-Spatz disease (HSD) is a rare autosomal-recessive hereditary disorder characterized by the early onset of progressive movement alterations, including dystonia, rigidity, choreoathetosis, and mental deterioration. HSD is also associated with a variety of psychiatric symptoms, primarily depression and mental deterioration. However, psychosis has rarely been reported as a major symptom of HSD. We report two siblings who presented psychiatric symptoms as major clinical presentations, accompanied by ataxic and spastic gait, dysarthria, and typical neuroimaging findings of HSD. A 14-year-old girl presented complex motor tics, stereotypic behavior and anxiety symptoms. Her older brother, a 16-year-old boy, presented prominent auditory hallucinations, persecutory delusions and social withdrawal symptoms. Psychiatric symptoms were improved after atypical antipsychotic treatment. HSD is a rare disease but should be carefully considered in the diagnosis of patients with both motor disorder and various psychiatric symptoms.
Adolescent ; Anxiety ; Delusions ; Depression ; Dysarthria ; Dystonia ; Gait Disorders, Neurologic ; Hallucinations ; Humans ; Neuroimaging ; Pantothenate Kinase-Associated Neurodegeneration ; Psychotic Disorders ; Rare Diseases ; Siblings ; Substance Withdrawal Syndrome ; Tics

Neurodegeneration with brain iron accumulation (NBIA) is a disorder characterized by various mixtures of extrapyramidal, pyramidal or psychiatric abnormalities associated with iron accumulation in the basal ganglia. The mutations in the pantothenate kinase gene (PANK2) were found in approximately two thirds of the patients with NBIA. We report three patients wtih NBIA, and two of them showed mutations in the PANK2 gene.
Basal Ganglia ; Brain ; Humans ; Iron ; Iron Metabolism Disorders ; Neuroaxonal Dystrophies ; Phosphotransferases ; Phosphotransferases (Alcohol Group Acceptor)

Adolescent ; Female ; Humans ; Magnetic Resonance Imaging ; Male ; Pantothenate Kinase-Associated Neurodegeneration ; diagnosis

OBJECTIVETo study pantothenate kinase 2 (PANK2) gene mutations in Chinese patients with Hallervorden-Spatz syndrome (HSS).

METHODSPANK2 gene mutations were detected by PCR, DNA sequence analyses, restriction enzyme digestion and PCR-single strand conformation polymorphism in 5 patients, 3 unaffected family members and 51 unrelated healthy persons.

RESULTSNovel compound heterozygous PANK2 gene mutations, A803G and T1172A, in exons 3 and 5, respectively, were found in one patient. At the same time, 3 types of single nucleotide polymorphisms, -38 t>a in 5'-UTR, IVS1+42 c>a and G77C in exon 1, were confirmed; among them, -38 t>a, IVS1+42 c>a, were first reported.

CONCLUSIONPANK2 gene mutations can cause HSS in Chinese patients.

Adolescent ; Adult ; Base Sequence ; Child ; China ; DNA Mutational Analysis ; Female ; Humans ; Male ; Middle Aged ; Mutation ; Pantothenate Kinase-Associated Neurodegeneration ; genetics ; Pedigree ; Phosphotransferases (Alcohol Group Acceptor) ; genetics ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Young Adult