Collagen XII-Related Myopathy: An Emerging Spectrum of Extracellular Matrix-Related Myopathy.

Collagen XII, a member of a protein family called fibril associated collagen with interrupted triple helices (FACIT), is an important component of extracellular matrix and is essential for bridging the neighbouring fibrils. Mutations in collagen XII have been recently described to cause a rare extracellular matrix-related myopathy in those whose phenotype resembles collagen VI-related dystrophies and were negative for pathogenic variants in COL6A genes. The authors report a 4-year old girl presented with a phenotype mimicking Ullrich congenital muscular dystrophy and genetically confirmed to have pathogenic variants in COL12A1 gene thus, expanding the phenotypic spectrum of COL12A1-related myopathy.

Clinical, Biochemical, Radiological, and Genetic Profile of Patients with Homocysteine Remethylation Pathway Defect and Spastic Paraplegia.

Objectives: The objective of this study is to describe the clinical, biochemical, radiological, and genetic profile of patients presenting with progressive spastic paraparesis due to homocysteine remethylation pathway defect. Methods: This was a retrospective study conducted by reviewing the medical records of patients with serum homocysteine levels >50 µmol/L between January 2015 and January 2019 at our hospital. We included patients presenting with progressive spastic paraparesis, having serum homocysteine >50 µmol/L with low or normal blood methionine suggesting disorders of homocysteine remethylation. Demographic details, clinical manifestations, biochemical abnormalities, neuroimaging findings, and genetic profile were analyzed. Results: A total of seven patients (M: F = 5:2) fulfilled the study eligibility criteria. The mean age at onset of the disease was 13.4 ± 2.4 years (range: 9-17 years). Spastic paraparesis was the presenting manifestation in 4/7 (57.1%) patients. Other manifestations included cognitive decline, poor scholastic performance, behavioral disturbances, seizures, and spastic bladder. Severe hyperhomocysteinemia (>100 µmol/L) was noted in 6/7 (85.7%) patients with median levels of serum homocysteine being 185.7 µmol/L (range: 85.78-338.5 µmol/L). Neuroimaging showed parieto-occipital predominant leukoencephalopathy in 5/7 (71.4%) and diffuse cerebral atrophy in 1/7 (14.2%). Genetic analysis in three patients revealed pathogenic missense variants c.459C >G (p.Ile153Met), c.973C >T (p.Arg325Cys), and c.1031G >T (p.Arg344Met) in MTHFR gene. All the patients received vitamin B12 (injection and oral), folic acid, and pyridoxine and two patients received betaine. At the last follow-up of a median duration of 12 months, there was a good clinical and biochemical response with reduction in the median value of serum homocysteine by 77.5 µmol/L. Conclusion: Evaluation of serum homocysteine and blood methionine in adolescents presenting with progressive spastic paraparesis gives clue to a treatable homocysteine remethylation disorders.

Lipid Storage Myopathy with Ketonuria: A Case of Fatty Acid Oxidation-Related Myopathy and Encephalopathy due to Multiple Acyl-CoA Dehydrogenase Deficiency.

Encephalopathy and Myopathy in children of varying ages can be due to variety of causes including Mitochondrial diseases, metabolic diseases like renal tubular acidosis, storage diseases as well as fatty acid oxidation (FAO) disorders. FAO related disorders have variable clinical presentation and manifest in different ages. They may present with hypoglycemia, effort intolerance, multi organ involvement with or without ketonuria. High degree of suspicion and appropriate investigations are mandatory for diagnosis. Here we describe an 11 Year old boy, born to non - consanguineous parents. Presented with exertion induced muscle pain and fatigue of 1year duration, which slowly progressed to severe weakness and vomiting. His reflexes were retained. Therefore metabolic vs inflammatory muscle diseases were considered. Patient had ketonuria with elevated blood levels of medium chain acyl carnitine and long chain acyl carnitine suggestive of MADD. Urine organic acid assessment showed elevated excretion of 2-hydroxyglutarate (2HG), adipate and arabitol. Muscle biopsy showed multiple fine vacuoles on Eosin- hematoxylin stained preparation. Modified Gomori - trichrome stain showed vacuolated fibers with red granular material consistent with ragged red fibers. Oil Red O stains showed vacuolated fibers with 'oil red O' positive material suggesting lipid storage. Above combination of features is consistent of MADD. Genetic evaluation is not done due to financial constraint. Patient was started on high dose riboflavin and carnitine, with which the child became near normal. Our patient is a case of MADD presenting as Reye's syndrome like features and showed excellent response to riboflavin, carnitine, dietary and life style changes. High degree of suspicion is lifesaving.

N-Methyl-D-Aspartate Encephalitis our Experience with Diagnostic Dilemmas, Clinical Features, and Outcome.

INTRODUCTION: A neuropsychiatric syndrome characterized by a wide spectrum of clinical manifestations. It is seen in patients with antibodies against NR1-NR2 heteromers of the NMDA receptor. As the spectrum is mainly psychiatric most patients are treated as psychiatric disease resulting in huge diagnostic delay. PATIENT AND METHODS: Here we describe 29 patients with NMDA encephalitis seen by the authors in the last five years. Percentage of Transfected cells showing granular cytoplasmic florescence was considered for positivity and severity both in CSF and serum. Their presenting diagnosis, clinical features and the dilemmas, alarming gaps, laboratory data, response to treatment and relapses are discussed. OBSERVATIONS: All patients presented with a spectrum of psychiatric symptoms varying from panic to severe aggression, seizures, chorea, hemiplegia, catatonia, mitgehen, mutism, delirium, mania and memory problems. EEG is invariably abnormal as against imaging. CONCLUSION: NMDA receptor mediated encephalitis should be suspected in all children and females of adolescent age with refractory neuropsychiatric syndrome. Both CSF and serum should be tested and regular follow up for relapses and neoplasms is mandatory.