CAPOS syndrome is an autosomal dominant neurological disorder caused by mutations in the ATP1A3 gene. Initial symptoms, often fever-induced, include recurrent acute ataxic encephalopathy in childhood, featuring cerebellar ataxia, optic atrophy, areflflexia, sensorineural hearing loss, and in some cases, pes cavus. This report details a case of CAPOS syndrome resulting from a maternal ATP1A3 gene mutation. Both the child and her mother exhibited symptoms post-febrile induction,including severe sensorineural hearing loss in both ears, ataxia, areflexia, and decreased vision. Additionally, the patient's mother presented with pes cavus. Genetic testing revealed a c. 2452G>A（Glu818Lys） heterozygous mutation in theATP1A3 gene in the patient . This article aims to enhance clinicians' understanding of CAPOS syndrome, emphasizing the case's clinical characteristics, diagnostic process, treatment, and its correlation with genotypeic findings.
Humans ; Child ; Female ; Cerebellar Ataxia/diagnosis* ; Talipes Cavus ; Hearing Loss, Sensorineural/diagnosis* ; Optic Atrophy/diagnosis* ; Mutation ; Phenotype ; Sodium-Potassium-Exchanging ATPase/genetics* ; Foot Deformities, Congenital ; Reflex, Abnormal

OBJECTIVE: To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome. METHODS: An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS). RESULTS: The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother. CONCLUSION The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.
Humans ; Infant ; Male ; alpha-Thalassemia/diagnosis* ; Ataxia Telangiectasia Mutated Proteins/genetics* ; East Asian People ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/diagnosis* ; Pedigree ; X-linked Nuclear Protein/genetics*

Niemann-Pick disease type C (NP-C) is a rare autosomal recessive neurovisceral lysosomal lipid storage disorder. The clinical manifestations of the disorder are variable. This report describes the case of a 27-month-old girl with NP-C whose condition had been misdiagnosed as spastic cerebral palsy (CP). She had spasticity, particularly at both ankles, and gait disturbance. Magnetic resonance imaging of the brain revealed findings suspicious of sequelae from a previous insult, such as periventricular leukomalacia, leading to the diagnosis of CP. However, she had a history of hepatosplenomegaly when she was a fetus and her motor development had deteriorated, with symptoms of vertical supranuclear gaze palsy, cataplexy, and ataxia developing gradually. Therefore, NP-C was considered and confirmed with a genetic study, which showed mutation of the NPC1 gene. Thus, if a child with CP-like symptoms presents with a deteriorating course and NP-C-specific symptoms, NP-C should be cautiously considered.
Ankle ; Ataxia ; Brain ; Cataplexy ; Cerebral Palsy ; Child ; Child, Preschool ; Diagnosis ; Female ; Fetus ; Gait ; Humans ; Infant, Newborn ; Leukomalacia, Periventricular ; Magnetic Resonance Imaging ; Muscle Spasticity ; Niemann-Pick Diseases ; Paralysis

BACKGROUND/AIMS: Although symptoms related to the pelvic floor, such as pelvic organ prolapse (POP) and lower urinary tract symptoms (LUTS), are common in patients with chronic constipation (CC), its impact is not clear. Our aims were to investigate the following (1) compare pelvic floor symptom related dysfunction in irritable bowel syndrome with constipation (IBS-C) and functional constipation (FC), and (2) symptom correlation with findings on anorectal manometry (ARM) and balloon expulsion test. METHODS: This was a retrospective analysis of patients with CC undergoing ARM. IBS-C and FC were diagnosed by Rome III criteria. Pelvic Floor Distress Inventory (PFDI-20) was used to measure pelvic floor symptom distress. Constipation Severity Scale was used to assess constipation severity. RESULTS: A total of 107 patients underwent ARM (64 FC, 43 IBS-C). The overall PFDI-20 score in IBS-C was higher compared with FC patients (118.0 vs 79.2, P = 0.001). In those with IBS-C, POP, LUTS, and colorectal symptoms subscales were all higher compared with FC patients (P < 0.05 for each). On multivariable regression, IBS-C (P = 0.001) and higher constipation severity (P = 0.001) were both independently associated with higher PFDI scores. ARM parameters and abnormal balloon expulsion test did not correlate with PFDI scores. CONCLUSIONS: Compared with FC patients, those with IBS-C have significantly higher distress from pelvic floor specific symptoms including POP and LUTS. Higher abdominal pain among IBS-C patients did not entirely explain these findings. A diagnosis of IBS-C and higher constipation severity correlated with PFDI-20 scores, but dyssynergia did not.
Abdominal Pain ; Arm ; Ataxia ; Constipation ; Defecation ; Diagnosis ; Humans ; Irritable Bowel Syndrome ; Lower Urinary Tract Symptoms ; Manometry ; Pelvic Floor ; Pelvic Organ Prolapse ; Retrospective Studies

GLUT1 deficiency is a rare neurometabolic disorder that can be effectively treated with ketogenic diet. However, this condition is underdiagnosed due to its nonspecific, overlapping, and evolving symptoms with age. We retrospectively reviewed the clinical course of nine patients diagnosed with GLUT1 deficiency, based on SLC2A1 mutations and/or glucose concentration in cerebrospinal fluid. The patients included eight boys and one girl who initially presented with seizures (44%, 4/9) or delayed development (44%, 4/9) before 2 years of age, except for one patient who presented with apnea as a neonate. Over the clinical course, all of the children developed seizures of the mixed type, including absence seizures and generalized tonic–clonic seizures. About half (56%, 5/9) showed movement disorders such as ataxia, dystonia, or dyskinesia. We observed an evolution of phenotype over time, although this was not uniform across all patients. Only one child had microcephaly. In five patients, ketogenic diet was effective in reducing seizures and movement symptoms, and the patients exhibited subjective improvement in cognitive function. Diagnosing GLUT1 deficiency can be challenging due to the phenotypic variability and evolution. A high index of clinical suspicion in pediatric and even older patients with epilepsy or movement disorders is key to the early diagnosis and treatment, which can improve the patient's quality of life.
Apnea ; Ataxia ; Cerebrospinal Fluid ; Child ; Clothing ; Cognition ; Dyskinesias ; Dystonia ; Early Diagnosis ; Epilepsy ; Epilepsy, Absence ; Female ; Glucose ; Humans ; Infant, Newborn ; Ketogenic Diet ; Microcephaly ; Movement Disorders ; Phenotype ; Quality of Life ; Retrospective Studies ; Seizures

Swallowing can be affected by a variety of systemic diseases. The etiology of dysphagia in the geriatric population is usually overlooked due mainly to a presumed diagnosis of presbyphagia or difficulty in revealing the direct cause. On the other hand, dysphagia can be a meaningful clinical sign of premalignant systemic disease. A 78-year-old man, without any prior medical or family history, was admitted with the chief complaint of dysphagia with recent aspiration pneumonia. Instrumental swallowing tests revealed a severe degree of dysphagia due to decreased laryngopharyngeal sensation and weakness of the pharyngeal constrictor muscles. Extensive workup, including electromyography and laboratory tests, revealed severe sensorimotor peripheral polyneuropathy related to monoclonal gammopathy. Monoclonal gammopathy of undetermined significance (MGUS) is a premalignant precursor of multiple myeloma, which is characterized by the proliferation of monoclonal proteins. These conditions are often associated with peripheral polyneuropathy, ataxia, and sometimes even muscle weakness. Although dysphagia can occur in other systemic disorders, such as vasculitis or paraneoplastic syndrome-related malignancies, there are few reports of dysphagia related to MGUS. The patient was followed up for three years. The MGUS showed no further progression, but the patient showed no improvement, indicating a protracted clinical course and poor prognosis when dysphagia is related to MGUS.
Aged ; Ataxia ; Deglutition ; Deglutition Disorders ; Diagnosis ; Electromyography ; Hand ; Humans ; Monoclonal Gammopathy of Undetermined Significance ; Multiple Myeloma ; Muscle Weakness ; Muscles ; Paraproteinemias ; Pneumonia, Aspiration ; Polyneuropathies ; Prognosis ; Sensation ; Vasculitis

BACKGROUND AND PURPOSE: The etiologies and frequencies of cerebellar ataxias vary between countries. Our primary aim was to determine the frequency of each diagnostic group of cerebellar ataxia patients in a Korean population. METHODS: We reviewed the medical records of patients who were being followed up between November 1994 and February 2016. We divided patients with cerebellar ataxias into familial and non-familial groups and analyzed the frequency of each etiology. Finally, we categorized patients into genetic, sporadic, secondary, and suspected genetic, but undetermined ataxia. RESULTS: A total of 820 patients were included in the study, among whom 136 (16.6%) familial patients and 684 (83.4%) non-familial cases were identified. Genetic diagnoses confirmed 98/136 (72%) familial and 72/684 (11%) nonfamilial patients. The overall etiologies of progressive ataxias comprised 170 (20.7%) genetic, 516 (62.9%) sporadic, 43 (5.2%) secondary, and 91 (11.1%) undetermined ataxia. The most common cause of ataxia was multiple-system atrophy (57.3%). In the genetic group, the most common etiology was spinocerebellar ataxia (152/170, 89.4%) and the most common subtype was spinocerebellar ataxia-3.38 of 136 familial and 53 of 684 sporadic cases (91/820, 11.1%) were undetermined ataxia. CONCLUSIONS: This is the largest epidemiological study to analyze the frequencies of various cerebellar ataxias in a Korean population based on the large database of a tertiary hospital movement-disorders clinic in South Korea. These data would be helpful for clinicians in constructing diagnostic strategies and counseling for patients with cerebellar ataxias.
Ataxia ; Atrophy ; Cerebellar Ataxia* ; Counseling ; Diagnosis ; Epidemiologic Studies ; Friedreich Ataxia ; Humans ; Korea ; Medical Records ; Spinocerebellar Ataxias ; Tertiary Care Centers

Previously, we defined DRD as a syndrome of selective nigrostriatal dopamine deficiency caused by genetic defects in the dopamine synthetic pathway without nigral cell loss. DRD-plus also has the same etiologic background with DRD, but DRD-plus patients have more severe features that are not seen in DRD because of the severity of the genetic defect. However, there have been many reports of dystonia responsive to dopaminergic drugs that do not fit into DRD or DRD-plus (genetic defects in the dopamine synthetic pathway without nigral cell loss). We reframed the concept of DRD/DRD-plus and proposed the concept of DRD look-alike to include the additional cases described above. Examples of dystonia that is responsive to dopaminergic drugs include the following: transportopathies (dopamine transporter deficiency; vesicular monoamine transporter 2 deficiency); SOX6 mutation resulting in a developmentally decreased number of nigral cells; degenerative disorders with progressive loss of nigral cells (juvenile Parkinson's disease; pallidopyramidal syndrome; spinocerebellar ataxia type 3), and disorders that are not known to affect the nigrostriatal dopaminergic system (DYT1; GLUT1 deficiency; myoclonus-dystonia; ataxia telangiectasia). This classification will help with an etiologic diagnosis as well as planning the work up and guiding the therapy.
Ataxia ; Classification ; Diagnosis ; Dopamine ; Dopamine Agents ; Dystonia* ; Humans ; Parkinson Disease ; Spinocerebellar Ataxias ; Vesicular Monoamine Transport Proteins

PURPOSE: To describe a technique for urodynamic diagnosis of detrusor sphincter dyssynergia (DSD) using urethral pressure measurements and examine potential associations between urethral pressure and bladder physiology among patients with DSD. METHODS: Multiple sclerosis (MS) and spinal cord injured (SCI) patients with known DSD diagnosed on videourodynamics (via electromyography or voiding cystourethrography) were retrospectively identified. Data from SCI and MS patients with detrusor overactivity (DO) without DSD were abstracted as control group. Urodynamics tracings were reviewed and urethral pressure DSD was defined based on comparison of DSD and control groups. RESULTS: Seventy-two patients with DSD were identified. Sixty-two (86%) had >20 cm H₂O urethral pressure amplitude during detrusor contraction. By comparison, 5 of 23 (22%) of control group had amplitude of >20 cm H₂O during episode of DO. Mean duration of urethral pressure DSD episode was 66 seconds (range, 10–500 seconds) and mean urethral pressure amplitude was 73 cm H₂O (range, 1–256 cm H₂O). Longer (>30 seconds) DSD episodes were significantly associated with male sex (81% vs. 50%, P=0.013) and higher bladder capacity (389 mL vs. 219 mL, P=0.0004). Urethral pressure amplitude measurements during DSD were not associated with significant urodynamic variables or neurologic pathology. CONCLUSIONS: Urethral pressure amplitude of >20 cm H2O during detrusor contraction occurred in 86% of patients with known DSD. Longer DSD episodes were associated with larger bladder capacity. Further studies exploring the relationship between urethral pressure measurements and bladder physiology could phenotype DSD as a measurable variable rather than a categorical observation.
Ataxia* ; Diagnosis* ; Electromyography ; Humans ; Male ; Multiple Sclerosis ; Pathology ; Phenotype ; Physiology ; Retrospective Studies ; Spinal Cord ; Spinal Cord Injuries ; Urinary Bladder ; Urodynamics*

Ataxia-telangiectasia (AT; OMIM 208900) is a rare autosomal recessive inherited progressive neurodegenerative disorder, with onset in early childhood. AT is caused by homozygous or compound heterozygous mutations in ATM (OMIM 607585) on chromosome 11q22. The average prevalence of the disease is estimated at 1 of 100,000 children worldwide. The prevalence of AT in the Republic of Korea is suggested to be extremely low, with only a few cases genetically confirmed thus far. Herein, we report a 5-year-old Korean boy with clinical features such as progressive gait and truncal ataxia, both ankle spasticity, dysarthria, and mild intellectual disability. The patient was identified as a compound heterozygote with two novel genetic variants: a paternally derived c.5288_5289insGA p.(Tyr1763*) nonsense variant and a maternally derived c.8363A>C p.(His2788Pro) missense variant, as revealed by next-generation sequencing and confirmed by Sanger sequencing. Based on claims data from the Health Insurance Review and Assessment Service Republic of Korea, we calculated the prevalence of AT in the Republic of Korea to be about 0.9 per million individuals, which is similar to the worldwide average. Therefore, we suggest that multi-gene panel sequencing including ATM should be considered early diagnosis.
Ankle ; Ataxia ; Ataxia Telangiectasia* ; Child ; Child, Preschool ; Databases, Genetic ; Dysarthria ; Early Diagnosis ; Gait ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Insurance, Health ; Intellectual Disability ; Male ; Muscle Spasticity ; Neurodegenerative Diseases ; Prevalence* ; Republic of Korea* ; Spinocerebellar Degenerations