Novel missense WFS1 variant causing autosomal dominant atypical Wolfram syndrome.

BACKGROUND: In contrast to the classic autosomal recessive Wolfram syndrome, Wolfram-like syndrome (WLS) is an autosomal dominant disease caused by heterozygous variants in the WFS1 gene. Here, we present deep phenotyping of a mother and son with a WFS1 variant NM_006005.3:c.2508 G > T, p. (Lys836Asn) detected with next-generation sequencing, which is novel at the nucleotide level. In this Greek family, the proband and mother had sensorineural hearing loss and mild non-progressive vision loss with optic nerve atrophy. An initial optic atrophy panel that did not test for WFS1 was unremarkable, but a broader inherited retinal dystrophy panel found the WFS1 variant. CONCLUSION: This study highlights the importance of including WFS1 sequencing in the evaluation of optic nerve atrophy to discover syndromic conditions.

Identification of degradation impurity of TGR5 receptor agonist-ZY12201 by LC-MS technique during force degradation study.

Forced degradation study is a systemic characterization of degradation products of active pharmaceutical ingredient (API) at conditions which posses more harsh environment that accelerates degradation of API. Forced degradation and stability studies would be useful in selection of proper, packaging material and storage conditions of the API. These are also useful to demonstrate degradation pathways and degradation products of the API and further characterisation of the degradation products using mass spectrometry. TGR5 is a G protein-coupled receptor, activation of which promotes secretion of glucagon-like peptide-1 (GLP-1) and modulates insulin secretion. The potent and orally bioavailable TGR5 agonist, ZY12201, shows activation of TGR5 which increase secretion of GLP-1 and help in lowering blood glucose level in animal models. Hence it is necessary to establish and study degradation pathway and stability of API for better handling and regulatory approval. Force degradation studies of ZY12201 have shown presence of one oxidative impurity during oxidative degradation in HPLC analysis. The oxidized product is further characterized by LC-MS to elucidate structure of impurity and characterize its degradation pathway. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s42452-021-04660-y.

A Rare Case of Cerebellar Progressive Multifocal Leukoencephalopathy due to Idiopathic CD4 Lymphocytopenia.

Progressive multifocal leukoencephalopathy (PML) is a demyelinating disorder caused by reactivation of JC virus during a time of cell mediated immune suppression. One potential rare cause of PML is Idiopathic CD4 lymphocytopenia (ICL) in which there is an unexplained deficit of CD4 T cells. We present a case of cerebellar PML in the absence of known immunosuppression leading to the diagnosis of ICL.

Atypical MOG antibody disease presenting with typical multiple sclerosis lesions.

Myelin oligodendrocyte glycoprotein (MOG) antibody disease is an autoimmune disease of the central nervous system associated with a serological antibody against MOG, a glycoprotein expressed on the outer membrane of myelin. It is solely found within the central nervous system in the brain, optic nerves and spinal cord. MOG antibody disease falls within the neuromyelitis optica spectrum disorders (NMOSD), however clinical characteristics appear distinct from aquaporin-4 antibody related disease and multiple sclerosis. It has predilection for causing recurrent optic neuritis and transverse myelitis. Accurate diagnosis is important to determine long term prognosis and suitable treatment. We describe the case of a 42 year old woman previously labelled as MS who demonstrated a variable presentation of MOG antibody disease.

Pseudotumor Cerebri Syndrome with Resolution After Discontinuing High Vitamin A Containing Dietary Supplement: Case Report and Review.

A 24-year-old non-obese, but slightly overweight, female presented with a two-week history of progressive severe headache associated with two days of blurry vision. Clinical exam was significant for bilateral papilledema and an enlarged blind spot on visual field testing. Contrast enhanced MRI head revealed no space occupying lesion. A lumbar puncture revealed an elevated opening pressure of 38 cm H2O with normal cerebrospinal fluid composition leading to a diagnosis of pseudotumor cerebri syndrome (PTCS). The patient lacked the typical risk factors of high body mass index or obvious antecedent medications; however, on subsequent questioning, she was chronically ingesting a high vitamin A containing weight loss dietary supplement (Thrive W® - Table 1), which we believe had caused intracranial hypertension. Discontinuation of the diet pill and treatment with acetazolamide led to marked improvement of her PTCS. This case highlights the fact that non-traditional products or medications with high vitamin A may cause pseudotumor cerebri, which treating physicians should assess for while dealing with non-obese PTCS patients.

Bilateral Radiation Optic Neuropathy Following Concurrent Chemotherapy and Radiation in Glioblastoma.

Radiation optic neuropathy (RON) is an iatrogenic complication that causes severe, irreversible vision loss within months to years following radiation to lesions close to the visual pathway. The authors describe a case of RON in glioblastoma after radio-sensitisation with temozolomide with sequential involvement of both optic nerves. This case provides a timeline for clinical and imaging findings with RON and specifically resolution of nerve enhancement. The authors also highlight the potential of an increase in incidence of RON in glioblastoma with advances in survival seen with greater use of second-line chemotherapy and even re-radiation.

Neuro-Ophthalmic Presentation of Neuro-Sweet Disease.

Acute febrile neutrophilic dermatosis (Sweet syndrome) is a systemic inflammatory condition usually associated with autoimmune or neoplastic processes and characterised by inflammatory dermatologic lesions such as erythematous plaques and papules associated with fever and leukocytosis. Neurological and ophthalmological involvement is rare. The authors describe an unusual case of Sweet syndrome associated with microscopic polyangiitis presenting with papilloedema, anterior uveitis, and skin rash. Years later, he developed acute posterior multifocal placoid pigment epitheliopathy. Treatment with immunosuppressive medications led to a relapsing remitting course with maximum benefit from use of steroids. The authors describe the difficulties in diagnosis and treatment of this rare case.