Manganese transport disorder: novel SLC30A10 mutations and early phenotypes.

BACKGROUND: SLC30A10 mutations cause an autosomal recessive disorder, characterized by hypermanganesaemia, polycythemia, early-onset dystonia, paraparesis, or late-onset parkinsonism, and chronic liver disease. This is the first identified inborn error of Mn metabolism in humans, reported in 10 families thus far. METHODS: Methods for this study consisted of clinical examination, neuroimaging studies (MRI), serum dosages, and SLC30A10 genetic analysis. RESULTS: We describe early disease manifestations (including videos) in 5 previously unreported Indian children, carrying novel homozygous SLC30A10 mutations. Gait and speech disturbances, falls, dystonias, and central hypotonia were the presenting neurological features, starting within the first 5 years of life. All children also had severe hypermanganesemia, polycythemia, variable degree of liver disease, and marked brain MRI T1 hyperintensities. CONCLUSIONS: Our findings expand the mutational and clinical spectra of this recently recognized disorder. An early diagnosis is warranted, because treatment with manganese-chelating agents, iron supplementation, or their combination might improve symptoms and prevent progression of this otherwise potentially fatal disease. © 2015 International Parkinson and Movement Disorder Society.

Clinical Profile and Treatment Outcomes of Hypermanganesemia with Dystonia 1 and 2 among 27 Indian Children.

Background: Hypermanganesemia with dystonia 1 and 2 (HMNDYT1 and 2) are rare, inherited disorders of manganese transport. Objectives: We aimed to describe clinical, laboratory features, and outcomes among children with HMNDYT. Methods: We conducted a retrospective multicenter study involving tertiary centers across India. We enrolled children between 1 month to 18 years of age with genetically confirmed/clinically probable HMNDYT. Clinical, laboratory profile, genetic testing, treatment details, and outcomes scored by treating physicians on a Likert scale were recorded. Results: We enrolled 27 children (19 girls). Fourteen harbored SLC30A10 mutations; nine had SLC39A14 mutations. The SLC39A14 cohort had lower median age at onset (1.3 [interquartile range (IQR), 0.7-5.5] years) versus SLC30A10 cohort (2.0 [IQR, 1.5-5.1] years). The most frequent neurological features were dystonia (100%; n = 27), gait abnormality (77.7%; n = 21), falls (66.7%; n = 18), and parkinsonism (59.3%; n = 16). Median serum manganese (Mn) levels among SLC39A14 (44.9 [IQR, 27.3-147.7] mcg/L) cohort were higher than SLC30A10 (29.4 [17.1-42.0] mcg/L); median hemoglobin was higher in SLC30A10 (16.3 [IQR, 15.2-17.5] g/dL) versus SLC39A14 cohort (12.5 [8.8-13.2] g/dL). Hepatic involvement and polycythaemia were observed exclusively in SLC30A10 variants. A total of 26/27 children underwent chelation with disodium calcium edetate. Nine demonstrated some improvement, three stabilized, two had marked improvement, and one had normalization. Children with SLC39A14 mutations had poorer response. Two children died and nine were lost to follow-up. Conclusions: We found female predominance. Children with SLC39A14 mutations presented at younger age and responded less favorably to chelation compared to SLC30A10 mutations. There is emerging need to better define management strategies, especially in low resource settings.

Multiple Sclerosis-Minimizing Errors in Radiological Diagnosis.

BACKGROUND: Multiple sclerosis is a chronic demyelinating disorder with a myriad of imaging and clinical features that overlap with number of other neurological conditions. Incorrect diagnosis poses a significant risk to patients, it may lead to delays in management, increased morbidity, and also adds to the financial cost. OBJECTIVE: The aim of this study was to highlight strategies for the efficient differentiation of multiple sclerosis from other diseases which may masquerade as MS clinico-radiologically. MATERIAL AND METHODS: A systematic literature review was conducted through online databases including PubMed and Medline. Relevant publications on radiological aspects of multiple sclerosis, white matter diseases and mimickers of Multiple sclerosis were included in the analysis. RESULTS: Common mimickers of MS include small vessel disease, acute disseminated encephalomyelitis, neuromyelitis optica, anti-MOG encephalomyelitis, vasculitis, and CADASIL. Contrast-enhanced MRI study performed using MS protocol on high strength MRI system evaluated following a structured protocol along with clinical correlation is effective in differentiating MS from its mimickers. CONCLUSIONS: Contrast-enhanced MRI performed on a high strength scanner using MS protocol with structured protocol for evaluation along, with a better collaboration between radiologists and clinicians may help in minimizing errors in diagnosis of multiple sclerosis.

Progressive multifocal leukoencephalopathy in a patient with idiopathic CD4+T lymphocytopenia.

Progressive multifocal leukoencephalopathy (PML) is demyelinating of central nervous system caused by JC virus infection and often occurs in immunodeficient individuals. We report progressive PML in a 30-year-old male with idiopathic severely depressed CD4+T lymphocyte count. He was sero-negative for human immunodeficiency virus (HIV) infection.

An unusual case with a missing parotid gland: A case report.

Unilateral or bilateral agenesis of the parotid gland is an uncommon condition with unclear aetiology. Only 22 cases of unilateral salivary agenesis have been reported excluding the present case. We present a case of a 4-year-old female child who presented with complaints of slight discoloration of her tongue and was referred for MRI to rule out any vascular malformation. Imaging revealed a complete absence of the right parotid gland. Hypertrophy of the sublingual gland and hypoplasia of the parotid gland on the opposite side was also noted, an unusual finding as the contralateral parotid showed compensatory hypertrophy in the other reported cases.

Recurrent tumefactive demyelination in a child.

A 13-year-old female presented with two episodes of hemiplegia and hemianopia involving opposite sides, each time associated with seizures. On both occasions, the magnetic resonance (MR) scan showed a giant demyelinating, peripherally enhancing lesion with mass effect. MR spectroscopy (MRS) was indistinguishable from a tumor. At the first episode, she had undergone tumor decompression but the histopathology revealed an acute demyelinating lesion with no evidence of tumor. Each time there was partial clinical recovery and resolution of the radiological lesion, the patient having received corticosteroids during both of the episodes. She also developed hemiballismus postoperatively which resolved on withdrawing phenytoin. It is suggested that a trial of corticosteroids be given in suspected tumefactive demyelinating lesions, although they may be indistinguishable from a tumor.

Imaging in tuberculosis.

Despite many advances in both diagnosis and treatment, tuberculosis still remains one of commonest causes of morbidity and mortality from any infectious cause in the world. Although the overall incidence and mortality rate for tuberculosis has decreased over the years, timely and accurate diagnosis of tuberculosis is essential for the health of the patient as well as the public. For the diagnosis of tuberculosis, a high degree of clinical suspicion is required, and this becomes much more important in high-risk populations. Tuberculosis may masquerade as any disease; therefore, tissue and microbiological assessment is sometimes important for establishing the diagnosis. However, in daily practice, the clinician and radiologist should be familiar with the imaging features of pulmonary and extrapulmonary tuberculosis, as well as manifestations of tuberculosis in immunocompromised patients. Imaging provides a very important role in the diagnosis and management of tuberculosis. Although chest X rays remain the basic imaging modality for pulmonary tuberculosis, computed tomography, magnetic resonance imaging, and nuclear medicine techniques, including positron emission tomography/computed tomography, are extremely helpful in the assessment of both pulmonary and extrapulmonary tuberculosis.

Syringomyelia-like manifestation of subacute combined degeneration.

A 32-year-old male presented with progressive weakness and numbness of both upper limbs of one-month duration. The patient had weakness and wasting of small muscles of both hands with weak grip. Sensory system revealed graded sensory loss to pain, temperature and touch in C5 to T1 distribution and vibration and joint position sense from C5 to C8 in the both upper limbs. There was areflexia in the upper limbs while there was no motor or sensory deficit in the lower limbs. The cortical potential on stimulation of posterior tibial nerve was prolonged on both sides. On MR imaging of the cervical spine there was iso to low intense lesion which was hyperintense on T2-weighted imaging along the dorsal aspect of the cord extending from C2 to C6 level. The axial images showed involvement of the posterior column. The serum vitamin B12 level was found to be low. The patient responded to parenteral cyanocobalamine therapy and the radiological lesion subsequently resolved.

MRI in H1N1 encephalitis.

Novel influenza A (H1N1) virus has been largely associated with respiratory complications. The exact frequency of neurological complications is not known, but are more common in children. There are very few reports of MRI findings in H1N1 encephalitis and none from India. The authors report MRI findings in an infant with H1N1 encephalitis. The diagnosis was made based on history, viral serological tests and imaging findings.