Clinical Spectrum of TGM6-Related Movement Disorders: A New Report with a Pooled Analysis of 48 Patients.

Background Spinocerebellar ataxias (SCAs) are a diverse group of progressive neurodegenerative disorders. Until now, more than 20 genes have been implicated to be associated with this phenotype and TGM6 is one of these genes, associated with spinocerebellar ataxia-35 (SCA-35). The majority of disease-causing variants in the TGM6 gene predominantly have been reported from China and Taiwan and the association with Parkinson's disease (PD) have also been reported recently. Methods We report the first Indian case with SCA-35 in a 16-year-old-boy with atypical age of onset at 9 years, prominent extrapyramidal features, intellectual disability, and a novel missense mutation in the TGM6 gene. We also reviewed and collated all previously published cases with pathogenic TGM6 variants. Results Including the index case, 54 cases were identified from 10 relevant articles in literature and 48 cases had adequate clinical details to be included in the pooled analysis. Around two-thirds of reported cases had SCA-35 phenotype, with cerebellar atrophy. Onset in the majority of cases was the fourth decade of life onwards. A proportion of SCA-35 cases also had spasmodic torticollis, impaired proprioception, extrapyramidal features, and myoclonic jerks. The patients with PD had often early-onset milder symptoms, slower progression, and favorable response to levodopa/carbidopa. One patient each presented with episodic ataxia and dystonic tremor of the upper limb. Most of the cases had missense mutations, without any definite hotspot or genotype-phenotype correlation. Conclusions TGM6 mutation should be suspected in patients with SCA like presentation, especially when it is accompanied by extrapyramidal features, spasmodic torticollis, impaired proprioception, or myoclonus.

Megaloblastic wobbliness: A reversible neurological condition.

BACKGROUND: Vitamin B12 deficiency has been associated with a very wide spectrum of neurologic manifestations and the majority of cases occur in infants, pregnant women, and elderly people. In children, common neurological complications include neuropathy, neuropsychiatric features, infantile tremor syndrome, developmental delay, cognitive decline, spastic paraparesis due to subacute combined degeneration of cord, seizures, encephalopathy, extrapyramidal features, and neuropathy. Vitamin B12 is known to cause sensory ataxia, along with impaired position and vibration sense, as well as variable spasticity, as a part of subacute combined degeneration of the spinal cord. However, only a few cases of isolated cerebellar ataxia caused by vitamin B12 deficiency have been reported in published literature. METHODS AND RESULTS: We are reporting a case of isolated cerebellar ataxia progressing over months in a 13-year-old boy. He also had associated knuckle hyperpigmentation, megaloblastic anemia and his magnetic resonance imaging of the brain was normal. Complete blood count showed hemoglobin of 8.6 gm/dl and peripheral smear showed macrovalocytes and few hypersegmented neutrophils. Serum vitamin B12 level was low (134 pg/mL). He was started on daily intramuscular vitamin B12 supplementation and he showed a favorable response after the first week. CONCLUSIONS: Clinicians need to consider vitamin B12 deficiency as one of the rare etiological possibilities in children presenting with isolated subacute onset/chronic ataxia, as supplementation of this vitamin is likely to cause a complete reversal of ataxia in such children.

Immunomodulatory effects of temperature and pH of water in an Indian freshwater sponge.

Eunapius carteri, a freshwater sponge of India, inhabits the ponds and lakes and experiences variations of temperature and pH of water throughout the year. Sponges bear evolutionary and ecological importance with limited information on their immunological attribute and adaptational resilience in a changing environment. This paper reports temperature and pH specific responses of immune related parameters in sponge maintained in the experimental conditions of laboratory. Innate immunological parameters like phagocytosis and generation of cytotoxic molecules like superoxide anion, nitric oxide and phenoloxidase activity were estimated in E. carteri at different environmentally realistic water temperatures (10, 20, 30 and 40°C) and pH (6.4, 7.4 and 8.4). Phagocytosis and cytotoxicity are established as important immune parameters of invertebrates. Calalase, an antioxidant enzyme and phosphatases are involved in pathogen destruction and are considered as components of innate immunity. Activities of catalase, acid and alkaline phosphatases were estimated in E. carteri at different thermal regimes and pH. Modulation of phagocytic and cytotoxic responses and the activities of catalase and phosphatases at different water temperatures and pH indicated temperature and pH specific immunological status of E. carteri. Present investigation deals with the effects of selected hydrological parameters on the fundamental immune related parameters in sponge indicating its adaptational plasticity. Immunological resilience of this species in the face of variation of water temperature and pH is thought to be a special adaptive feature of sponge, a reported "living fossil".

Density shift, morphological damage, lysosomal fragility and apoptosis of hemocytes of Indian molluscs exposed to pyrethroid pesticides.

Bellamya bengalensis (Gastropoda: Prosobranchia) and Lamellidens marginalis (Bivalvia: Eulamellibranchiata) are the molluscs of Indian freshwater ecosystem and important biological resources. These edible species bear economical, ecological, nutritional and medicinal importance. Natural habitat of these organisms is under the ecological threat of contamination by cypermethrin and fenvalerate, the common pyrethroid pesticides of India. Hemocytes are chief immunoeffector cells of molluscs which exhibit responsiveness against environmental toxins and perform diverse immunological functions including phagocytosis, encapsulation and cytotoxicity. Experimental exposure of cypermethrin and fenvalerate resulted in significant shift in density and morphological damage in hemocytes of B. bengalensis and L. marginalis respectively. Pyrethroid induced fragility and destabilization of hemocyte lysosomal membrane was recorded and proposed as an indication of toxin induced stress in molluscs. Apoptosis is an immunologically important cellular response which is modulated by environmental toxins. Pyrethroid exposure suppressed the physiological level of apoptosis and necrosis in hemocytes of B. bengalensis and L. marginalis indicating possible impairment of apoptosis mediated immunoprotection. Differential responses of B. bengalensis and L. marginalis hemocytes may be due to species specificity, toxin specificity, nonidentical immune strategies of Gastropoda and Bivalvia, specific habitat preference and related ecological niches.

A comparative analyses of morphological variations, phagocytosis and generation of cytotoxic agents in flow cytometrically isolated hemocytes of Indian molluscs.

A comparative analyses of hemocytes of molluscs, Pila globosa (Gastropoda: Prosobranchia), Bellamya bengalensis (Gastropoda: Prosobranchia) and Lamellidens marginalis (Bivalvia: Eulamellibranchiata) were carried out for morphotype and subpopulation identification, analyses of phagocytosis and generation of cytotoxic agents. Flow cytometry and microscopic analyses of hemocytes revealed the existence of agranulocytes (blast like cells, round hyalinocytes and spindle hyalinocytes), semigranulocytes (semigranular asterocytes and round semigranulocytes) and granulocytes (round granulocytes, spindle granulocytes and granular asterocytes) as three morphotypes. In P. globosa, granulocytes and semigranulocytes and in B. bengalensis granulocytes and agranulocytes are the chief phagocytes and major producers of superoxide anion and nitric oxide. In L. marginalis, granulocytes were identified as principal phagocytes with prominent activity of superoxide anion and nitric oxide. Highest activity of phenoloxidase was recorded in the agranulocytes of P. globosa with moderate activities among other morphotypes of all three species. Differential result may be due to species specific response, non-identical habitat preference and related adaptation of the species to their different ecological niches.