Catching the Culprit: How Chorea May Signal an Inborn Error of Metabolism.

Background: Movement disorders, particularly chorea, are uncommon in inborn errors of metabolism, but their identification is essential for improved clinical outcomes. In this context, comprehensive descriptions of movement disorders are limited and primarily derived from single cases or small patient series, highlighting the need for increased awareness and additional research in this field. Methods: A systematic review was conducted using the MEDLINE database and GeneReviews. The search included studies on inborn errors of metabolism associated with chorea, athetosis, or ballismus. The review adhered to PRISMA guidelines. Results: The systematic review analyzed 76 studies out of 2350 records, encompassing the period from 1964 to 2022. Chorea was observed in 90.1% of the 173 patients, followed by athetosis in 5.7%. Various inborn errors of metabolism showed an association with chorea, with trace elements and metals being the most frequent. Cognitive and developmental abnormalities were common in the cohort. Frequent neurological features included seizures, dysarthria, and optic atrophy, whereas non-neurological features included, among others, facial dysmorphia and failure to thrive. Neuroimaging and biochemical testing played crucial roles in aiding diagnosis, revealing abnormal findings in 34.1% and 47.9% of patients, respectively. However, symptomatic treatment efficacy for movement disorders was limited. Discussion: This study emphasizes the complexities of chorea in inborn errors of metabolism. A systematic approach with red flags, biochemical testing, and neuroimaging is required for diagnosis. Collaboration between neurologists, geneticists, and metabolic specialists is crucial for improving early detection and individualized treatment. Utilizing genetic testing technologies and potential therapeutic avenues can aid in the improvement of patient outcomes.

Dystonic posturing with athetoid movements in stroke without thalamic lesion.

Complex hyperkinetic movement disorders are a rare complication of stroke, frequently involving posterolateral contralateral thalamic lesions. One of the proposed mechanisms for these presentations is proprioceptive impairment, hence not involving deregulation of the basal ganglia-thalamocortical circuits. We report a patient who presented with dystonic posturing and athetoid movements with onset 2 years after right frontoparietotemporal stroke. Brain MRI showed no thalamic lesion. Based on the phenomenology, a diagnosis of pseudochoreoathetosis was proposed. To our knowledge, this is the first case report of poststroke pseudochoreoathetosis without thalamic involvement.

A case of brain-lung-thyroid syndrome. / 脑-肺-ç”²çŠ¶è ºç»¼åˆå¾1例.

Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.

Spectrum of Movement Disorders Among Children With Subacute Sclerosing Panencephalitis: A Cross-Sectional Study.

Background: Subacute sclerosing panencephalitis is a progressive devastating condition due to persistence of mutant measles virus, affecting children and adolescents, characterised by myoclonus, seizures, and neuropsychiatric issues. Movement disorders apart from myoclonus are reportedly uncommon. We aimed to describe frequency and proportion of movement disorders among children with subacute sclerosing panencephalitis, hypothesizing that these occur more frequently than previously reported. Methods: In this cross-sectional study, we enrolled children with subacute sclerosing panencephalitis between 1 month and 18 years of age who fulfilled the diagnosis of subacute sclerosing panencephalitis as per modified Dyken criteria, and examined them for movement disorders. We also assessed their clinical profile and disease severity via Jabbour staging and modified Rankin Scale score. We compared demographic, clinical, and laboratory features of children with and without movement disorders. Results: We enrolled 50 children (36 males; 72%) (age range 1.5-14 years). Of these, 28 (56%) had movement disorders. Among movement disorders, the most frequent was myoclonus (92%), followed by ataxia (9; 18%), chorea-athetosis (7; 14%), dystonia (6; 12%), tremor (4; 8%), repetitive behavior (4; 8%), and parkinsonism (3; 6%). Movement disorders were the presenting feature of subacute sclerosing panencephalitis among 7 children. There were no significant differences in clinical or laboratory features among children with and without movement disorders. Conclusions: Movement disorders were frequent in subacute sclerosing panencephalitis. Hyperkinetic disorders were dominant. Dystonia and chorea-athetosis occurred more commonly among nonmyoclonus movement disorders. Movement disorders may manifest even in earlier stages of subacute sclerosing panencephalitis and may be the heralding feature. Recognition of these features is important to plan management and reduce morbidity.

A case of brain-lung-thyroid syndrome / 中南大学学报(医学版)

Brain-lung-thyroid syndrome is a rare autosomal dominant disorder. More than 100 cases have been reported worldwide, but few cases have been reported in China. In December 2018, a boy with brain-lung-thyroid syndrome, aged 3 years and 10 months, was admitted to Xiangya Hospital of Central South University due to repeated cough for more than 3 years. In infancy of the boy, psychomotor retardation, repeated cough, and hypothyroidism were found. Gene detection showed that there was c.927delc heterozygous variation in NKX2-1 gene (NM-001079668: exon3: c.927delC). The variation of this gene locus has not been reported in relevant literature so far, which indicates a new mutation. According to the above clinical manifestations and examination results, the boy was diagnosed as brain-lung-thyroid syndrome, which mainly characterized by nervous system disorders, accompanied by respiratory manifestations and hypothyroidism. The boy was treated with oral dopasehydrazine to relieve tremor and levothyroxine sodium tablets to relieve hypothyroidism. Anti-infection, atomization, rehabilitation training and other symptomatic supporting treatment were also administered. The boy's language and movement have improved, the thyroid hormone level is normal, and there are still repeated respiratory tract infections.

Crossed Choreoathetosis Caused by Unilateral Thalamic Hemorrhage.

In general, involuntary movements after stroke are due to a disturbance in the unilateral cortico-basal ganglia loop and appear contralateral to stroke lesions. Crossed involuntary movements after unilateral stroke are very rare. We observed a case of crossed involuntary movements in the left upper limb and right lower limb after a right thalamic hemorrhage expanded to the right subthalamic nucleus. We considered a possible three-step theory as the basis of crossed choreoathetosis. This case informs our better understanding of the cortico-basal ganglia loop and involuntary movements after stroke.

Improving the objectivity of the current World Para Swimming motor coordination test for swimmers with hypertonia, ataxia and athetosis using measures of movement smoothness, rhythm and accuracy.

The current protocol for classifying Para swimmers with hypertonia, ataxia and athetosis involves a physical assessment where the individual's ability to coordinate their limbs is scored by subjective clinical judgment. The lack of objective measurement renders the current test unsuitable for evidence-based classification. This study evaluated a revised version of the Para swimming assessment for motor coordination, incorporating practical, objective measures of movement smoothness, rhythm error and accuracy. Nineteen Para athletes with hypertonia and 19 non-disabled participants performed 30 s trials of bilateral alternating shoulder flexion-extension at 30 bpm and 120 bpm. Accelerometry was used to quantify movement smoothness; rhythm error and accuracy were obtained from video. Para athletes presented significantly less smooth movement and higher rhythm error than the non-disabled participants (p < 0.05). Random forest algorithm successfully classified 89% of participants with hypertonia during out-of-bag predictions. The most important predictors in classifying participants were movement smoothness at both movement speeds, and rhythm error at 120 bpm. Our results suggest objective measures of movement smoothness and rhythm error included in the current motor coordination test protocols can be used to infer impairment in Para swimmers with hypertonia. Further research is merited to establish the relationship of these measures with swimming performance.

Brain-lung-thyroid syndrome in a neonate with argininosuccinate lyase deficiency.

Argininosuccinate lyase (ASL) deficiency is a rare autosomal recessive urea cycle disorder. The severe neonatal-onset form is characterised by hyperammonaemia in the first days of life and manifests with a variety of severe symptoms. However, an index of suspicion for additional or alternative diagnoses must be maintained when the patient's presentation is out of keeping with expected manifestations and course. We present a case of a neonate with ASL deficiency and concomitant hypotonia, severe respiratory distress, pulmonary hypertension, systemic hypotension and congenital hypothyroidism. The patient was investigated and subsequently diagnosed with brain-lung-thyroid syndrome, caused by a mutation in the NKX2-1 gene.

[Brain-lung-thyroid syndrome in a newborn with deletion 14q12-q21.1]. / Síndrome cerebro-pulmón-tiroides en un recién nacido con deleción 14q12-q21.1.

INTRODUCTION: In newborns with respiratory failure and interstitial lung disease, it should be approached as chILD (Childhood Interstitial Lung Disease) syndrome to rule out alterations in surfactant metabolism and brain-lung-thyroid syndrome caused by pathogenic variants in the NKX2-1 gene. OBJECTIVE: To pre sent a newborn with chILD syndrome and a large deletion in chromosome 14q12-q21.1. CLINICAL CASE: Newborn patient with respiratory distress since birth, chILD syndrome, and hypothyroidism, in which brain-lung-thyroid syndrome was suspected. He also presented seizures, minor and ma jor abnormalities on physical examination. Microarray analysis revealed a 14.7 Mb deletion in the chromosome 14q12-q21.1, which includes the NKX2-1 gene. CONCLUSION: The brain-lung-thyroid syndrome should be considered in newborns with respiratory distress syndrome and diffuse lung disease (chILD syndrome), especially if they present hypotonia, choreoathetosis, or hypothyroidism. Diagnosis confirmation requires genetic analysis, even more, when there are other abnormalities not explained by the suspected syndrome.

Cluster analysis of impairment measures to inform an evidence-based classification structure in RaceRunning, a new World Para Athletics event for athletes with hypertonia, ataxia or athetosis.

RaceRunning enables athletes with limited or no walking ability to propel themselves independently using a three-wheeled frame that has a saddle, handle bars and a chest plate. For RaceRunning to be included as a para athletics event, an evidence-based classification system is required. This study assessed the impact of trunk control and lower limb impairment measures on RaceRunning performance and evaluated whether cluster analysis of these impairment measures produces a valid classification structure for RaceRunning. The Trunk Control Measurement Scale (TCMS), Selective Control Assessment of the Lower Extremity (SCALE), the Australian Spasticity Assessment Scale (ASAS), and knee extension were recorded for 26 RaceRunning athletes. Thirteen male and 13 female athletes aged 24 (SD = 7) years participated. All impairment measures were significantly correlated with performance (rho = 0.55-0.74). Using ASAS, SCALE, TCMS and knee extension as cluster variables in a two-step cluster analysis resulted in two clusters of athletes. Race speed and the impairment measures were significantly different between the clusters (p < 0.001). The findings of this study provide evidence for the utility of the selected impairment measures in an evidence-based classification system for RaceRunning athletes.

Characterization of the GABRB2-Associated Neurodevelopmental Disorders.

OBJECTIVE: We aimed to characterize the phenotypic spectrum and functional consequences associated with variants in the gene GABRB2, coding for the γ-aminobutyric acid type A (GABAA ) receptor subunit ß2. METHODS: We recruited and systematically evaluated 25 individuals with variants in GABRB2, 17 of whom are newly described and 8 previously reported with additional clinical data. Functional analysis was performed using a Xenopus laevis oocyte model system. RESULTS: Our cohort of 25 individuals from 22 families with variants in GABRB2 demonstrated a range of epilepsy phenotypes from genetic generalized epilepsy to developmental and epileptic encephalopathy. Fifty-eight percent of individuals had pharmacoresistant epilepsy; response to medications targeting the GABAergic pathway was inconsistent. Developmental disability (present in 84%) ranged from mild intellectual disability to severe global disability; movement disorders (present in 44%) included choreoathetosis, dystonia, and ataxia. Disease-associated variants cluster in the extracellular N-terminus and transmembrane domains 1-3, with more severe phenotypes seen in association with variants in transmembrane domains 1 and 2 and the allosteric binding site between transmembrane domains 2 and 3. Functional analysis of 4 variants in transmembrane domains 1 or 2 (p.Ile246Thr, p.Pro252Leu, p.Ile288Ser, p.Val282Ala) revealed strongly reduced amplitudes of GABA-evoked anionic currents. INTERPRETATION: GABRB2-related epilepsy ranges broadly in severity from genetic generalized epilepsy to developmental and epileptic encephalopathies. Developmental disability and movement disorder are key features. The phenotypic spectrum is comparable to other GABAA receptor-encoding genes. Phenotypic severity varies by protein domain. Experimental evidence supports loss of GABAergic inhibition as the mechanism underlying GABRB2-associated neurodevelopmental disorders. ANN NEUROL 2021;89:573-586.

Hypoxaemia and interstitial lung disease in an infant with hypothyroidism and hypotonia.

A 7-month-old-term male infant presented with cough, tachypnoea, hypoxaemia and post-tussive emesis. Clinical history was significant for respiratory failure and pulmonary hypertension in the neonatal period requiring assisted ventilation, congenital hypothyroidism, mild hypotonia, recurrent respiratory infections, hypoxaemia requiring supplemental oxygen and nasogastric tube feeds. Physical examination showed tachypnoea, coarse bilateral breath sounds and mild hypotonia. Chest radiograph revealed multifocal pulmonary opacities with coarse interstitial markings and right upper lobe atelectasis. Following antibiotic therapy for suspected aspiration pneumonia, chest CT scan was performed and showed multiple areas of pulmonary consolidation and scattered areas of bilateral ground-glass opacities. Genetic studies showed a large deletion of chromosome 14q13.1-14q21.1, encompassing the NK2 homeobox 1 (NKX2-1) gene consistent with a diagnosis of brain-thyroid-lung (BTL) syndrome. Our case highlights the importance of genetic studies to diagnose BTL syndrome in infants with hypothyroidism, hypotonia and lung disease.

Eye Gaze Gaming Intervention in Children with Dyskinetic Cerebral Palsy: A Pilot Study of Task Performance and Its Relation with Dystonia and Choreoathetosis.

OBJECTIVES: To investigate the operational competences screen navigation and dwell function underlying eye gaze performance, and the relation of dystonia and choreoathetosis with eye gaze performance in children with dyskinetic cerebral palsy (DCP). METHODS: During a 5-week intervention, ten participants with DCP played eye gaze video games daily for 30 minutes. Six games were used to assess task performance, fixation count, and eye movement accuracy during four measurements. Dystonia and choreoathetosis were evaluated using the Dyskinesia Impairment Scale. RESULTS: Eye gaze performance improved over time (p = .013). Moderate to strong within-subject correlations were found between eye movement accuracy and task performance, and between eye movement accuracy and fixation count. No significant correlations were found with the movement disorders. CONCLUSIONS: Eye gaze technology shows great potential to be a successful computer interface for children with severe DCP, thereby potentially improving their communication skills, participation levels, and quality of life.

Combined mutations of NKX2-1 and surfactant protein C genes for refractory low oxyhemoglobin saturation and interstitial pneumonia: A case report.

RATIONALE: Mutations of the NKX2-1 gene are associated with brain-lung-thyroid syndrome, which is characterized by benign hereditary chorea, hypothyroidism, and pulmonary disease with variable presentation. Surfactant protein C (SFTPC) gene mutations result in chronic interstitial lung disease in adults or severe neonatal respiratory distress syndrome. PATIENT CONCERNS: Recurrent hypoxemia was observed shortly after birth in a baby at a gestational age of 40 weeks and birth weight of 3150 g. The need for respiratory support gradually increased. He had hypothyroidism and experienced feeding difficulties and irritability. DIAGNOSIS: Genetic examination of the peripheral blood revealed combined mutations of the NKX2-1 and SFTPC genes. INTERVENTIONS: The patient was administered respiratory support, antibiotics, low-dose dexamethasone, supplementary thyroxine, venous nutrition, and other supportive measures. OUTCOMES: The patient's guardian stopped treatment 3 months after commencement of treatment, due to the seriousness of his condition and the patient died. LESSONS: Combined mutations of NKX2-1 and SFTPC genes are very rare. Thus, idiopathic interstitial pneumonia with hypothyroidism and neurological disorders require special attention.