scholarly journals Alpers- and MNGIE-like disease with disturbed CSF folate transport and an unusual mode of genetic transmission of POLG mutations: a case report

2021 ◽  
Vol 1 (1) ◽  
Author(s):  
Rudolf Korinthenberg ◽  
Janbernd Kirschner ◽  
Matthias Eckenweiler ◽  
Robert Steinfeld ◽  
Nana Nino Tatishvili ◽  
...  
Keyword(s):  
Folate Receptor ◽  
Systemic Disease ◽  
Epileptic Seizures ◽  
The Other ◽  
Buccal Swab ◽  
Compound Heterozygous ◽  
Folate Transport ◽  
Lethal Outcome ◽  
Germline Mosaicism ◽  
Genetic Transmission

We report about a family with three of five siblings affected by a variable remitting-relapsing disease with epileptic seizures, coma and abdominal crises, and lethal outcome in all. In the youngest son and in one of his deceased brothers we identified two disease causing compound heterozygous POLG mutations. One of these was inherited from the mother, but the other was absent in the father`s blood, saliva, buccal swab and hair bulbs although his paternity was proven genetically. Thus, we assume germline mosaicism for this mutation in the father. Very low 5-methyltetrahydrofolate (5-MTHF) and absence of folate receptor-alpha was repeatedly found in the CSF of the youngest brother indicating a secondary cerebral folate transport deficiency. Folinic acid supplementation over 18 months resulted in some improvement of the neurological condition; however, it did not prevent progression of the systemic disease.

scholarly journals Mucopolysaccharidosis type I - Clinical and genetic characteristics of Romanian patients

2020 ◽  
Vol 28 (3) ◽  
pp. 279-286
Author(s):  
Camelia Alkhzouz ◽  
Cecilia Lazea ◽  
Diana Miclea ◽  
Carmen Asavoaie ◽  
Ioana Nascu ◽  
...  
Keyword(s):  
Severe Form ◽  
The Other ◽  
Compound Heterozygous ◽  
Type I ◽  
Ophthalmological Examination ◽  
Mucopolysaccharidosis Type ◽  
Hurler Syndrome ◽  
Mucopolysaccharidosis Type I ◽  
Genetic Characteristics ◽  
Mps I

AbstractBackground: Mucopolysaccharidosis type I (MPS I) is an autosomal recessive lysosomal storage disorder caused by a deficiency of α-L-iduronidase (IDUA), which leads to the accumulation of partially digested glycosaminoglycans (dermatan sulfate and heparan sulfate) in the lysosomes and induces multisystemic alteration. Hurler (severe), Scheie (mild), and Hurler/Scheie (intermediate) syndromes are clinical subtypes of MPS-I. To date, more than 290 IDUA mutations have been reported. The purpose of this study was to present the clinical and genetic characteristics of Romanian MPS I syndrome patients and their genotype-phenotype correlation.Patients and methods: Seven patients (5 girls and 2 boys) with MPS type I, belonging to 4 unrelated families, aged 0,75-17.9 years, were enrolled. The study methods consisted in: clinical and standard auxological assessment, bone radiographs, joint ultrasonography, goniometry, neurological and psychological evaluation, hepatic and splenic ultrasonography, cardiological evaluation, otorhinolaryngology examination, ophthalmological examination, spirometry, α-L-iduronidase enzyme activity assay and molecular analysis.Results: The seven patients originated from 4 unrelated families, three patients with severe, two patients with intermediate and two with attenuated clinical phenotype. Each patient presented the classical picture of MPS type I picture, represented by: variable coarse facial features, arthropathy, hepatosplenomegaly, cardiac involvement, respiratory dysfunction and neurological impairment. Five patological variants, three point mutations (p.Q70 *, p.I238Q and p.K324R), two deletion c.1045_1047delGAC, c.46_57delTCGCTCCTG) and an insertion (c.1389 insC) were identified in both alleles of the ADUA gene in homozygous or heterozygous form. Two novel mutations (p.K324R and c.1389 insC) were reported. The p.Q70*(c.208C>T) variant was identified in 2 families with severe form of disease (Hurler syndrome) in homozygous status in one family and in compound heterozygous status in the other family.Conclusion: The p.Q70* missense variant was the most frequent, correlated in all the cases who presented it with severe form, Hurler syndrome, the other mutations being usually isolated and particular for each patient, associated in our patients with less severe MPS I phenotype, as Hurler-Scheie or Scheie syndrome. The results of this study indicated the mutational heterogeneity of the IDUA gene and the difficulty to indicate some correlation between the genotype and phenotype in MPS I patients.

scholarly journals Protein-to-creatinine urinary in the early diagnosis of renal injury in canine pyometra

2019 ◽  
Vol 39 (3) ◽  
pp. 186-191
Author(s):  
Marcos C. Sant’Anna ◽  
Guilherme F. Martins ◽  
Karina K.M.C. Flaiban ◽  
Luiz G.C. Trautwein ◽  
Maria I.M. Martins
Keyword(s):  
Renal Failure ◽  
Chronic Renal Failure ◽  
Renal Injury ◽  
Renal Damage ◽  
Systemic Disease ◽  
The Other ◽  
Control Group ◽  
Creatinine Ratio ◽  
Renal Lesions ◽  
Tubular Cells

ABSTRACT: Kidney disease that affects bitches with pyometra may lead patients to develop chronic renal failure even after pyometra treatment. Therefore, several studies have sought to clarify the gaps in the understanding of the pathogenesis of renal injury in pyometra. Identification of early detection markers for renal damage, which can predict and identify the prognosis of the disease, is very important. Proteinuria analysis can diagnose kidney damage, since proteins such as albumin are not filtered through the glomerulus and those that undergo glomerular filtration are almost completely reabsorbed by tubular cells. The objective of this study was to evaluate whether the urinary protein-to-creatinine ratio (UPC) can detect renal injury in bitches with pyometra before development of azotemia. For this, 44 bitches with pyometra were divided into two groups: bitches with azotemic piometra (A, n=15, creatinine >1.7) and bitches with non-azotemic pyometra (NA, n=29). The two groups were compared to the control group (CG, n=12), which had no signs of systemic disease. All animals underwent blood and urine tests. Leukocytosis was more evident in bitches in the A group than in the other groups. This shows that the inflammatory response may be associated with the pathogenesis of renal injury. The median UPC in bitches with pyometra was significantly higher than in the CG, with a median above the reference values. In conclusion, the UPC can be used in bitches with pyometra to detect renal damage before the development of azotemia. It has been suggested that the UPC of bitches with pyometra should be followed through during the postoperative period so that permanent renal lesions secondary to pyometra can be diagnosed and treated properly before the development of azotemia.

scholarly journals Trigeminal Amyloidoma: A Report of Two Cases and Review of the Literature

2019 ◽  
Vol 81 (06) ◽  
pp. 620-626
Author(s):  
Amy Swanson ◽  
Caterina Giannini ◽  
Michael Link ◽  
Jamie Van Gompel ◽  
John Wald ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Trigeminal Nerve ◽  
Systemic Disease ◽  
Protein Characterization ◽  
The Other ◽  
Sensory Loss ◽  
Meckel’S Cave ◽  
Extensive Evaluation ◽  
Amyloid Deposits ◽  
Meckel's Cave

AbstractCerebral amyloidomas, characterized by localized amyloid deposits in the nervous system in the absence of systemic disease, are rare. These typically consist of immunoglobulin light chain (AL)-type, predominantly lambda. Trigeminal nerve involvement is exceptionally rare with only 21 previously reported cases, three with bilateral disease. We report two additional cases of amyloid localized to Meckel’s cave with secondary involvement of the trigeminal nerves bilaterally, with protein characterization by mass spectrometry. The patients, both females, 39 and 49-years-old, respectively, presented with the insidious onset of progressive trigeminal neuropathy, including pain and numbness with sensory loss, refractory to medical therapy. One patient experienced bilateral symptoms. Magnetic resonance imaging demonstrated abnormal thickening and contrast enhancement along Meckel’s cave bilaterally in both cases. The clinical differential diagnosis included benign neoplasms and inflammatory disorders. At the time of biopsy, the trigeminal nerve was noted to be enlarged and multinodular in one case and associated with abnormal soft tan tissue in the other case. Microscopically, the nerve biopsies showed extensive Congo red-positive amyloid deposits. Liquid chromatography tandem mass spectrometry demonstrated that the amyloid was of (AL)-type in both cases (AL [kappa] in one case and AL [lambda] in the other). After extensive evaluation, there was no evidence of systemic involvement. Both patients received localized radiotherapy for their refractory symptoms. One patient has stable symptomatology and imaging. No follow-up is available for the other patient.

The Phenotypic Expression of Homozygous and Compound Heterozygous Factor V R506Q (Factor V Leiden, FVL) and Factor II A20210G: Ten Years Experience At a Referral Center

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 5252-5252
Author(s):  
Hamid A B Al-Mondhiry ◽  
Thomas P Nifong ◽  
Mary Elaine Eyster
Keyword(s):  
Recurrent Events ◽  
Conflicts Of Interest ◽  
Phenotypic Expression ◽  
Factor V Leiden ◽  
The Other ◽  
Compound Heterozygous ◽  
Factor V ◽  
Degree Relative ◽  
Referral Center ◽  
Factor Ii

Abstract Abstract 5252 Heterozygous Factor V Leiden, the most common inherited thrombotic disorder with an estimated incidence of about 5% in Caucasian population, poses a moderate risk of first venous thromboembolic (VTE) event. The homozygous and compound heterozygous states are comparatively rare but are thought to be associated with high risk of recurrent VTE. This report describes ten years experience with homozygous and compound heterozygous FVL and Factor II A20210G at a major referral center in central Pennsylvania, USA. Between January 2000 and December 2010, 31 homozygous F VL patients, 2 homozygous FII A20210G, 10 compound heterozygous FVL and F II A20210G and 6 compound heterozygous F VL and protein C (PC), protein S (PS) or antithrombin (AT) deficiency were encountered. The reasons for referral were personal or family history of VTE or a first degree relative diagnosed with any of these conditions. Among these patients, 5 homozygous F VL, 1 compound heterozygous F VL and F II A20210G, and 1 compound heterozygous factor VL and PC deficiency remained free of VTE at age 17–64 years, even though they were exposed to prothrombotic conditions, e.g., surgery, hormones or pregnancy. Two compound heterozygous F VL and PS deficient patients suffered ischemic strokes, one at age 3 ½ years and the other at age 45 years, but no VTE. The other patients suffered lower extremity deep vein thrombosis and/or pulmonary embolism or visceral thrombosis. Most had recurrent events. Our experience highlights the serious thrombotic risks associated with homozygous and compound heterozygous F VL and F II A20210G status but also indicates that some patients remain thrombosis free despite exposure to additional prothrombotic conditions. However, because of referral bias this series of patients may not truly reflect the overall occurrence of VTE in patients with homozygous or compound heterozygous inherited thrombophilia. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Necrosis of the duodenum resulting from acute necrotising pancreatitis and treated with complete duodenopancreatectomy

2005 ◽  
Vol 133 (11-12) ◽  
pp. 510-513
Author(s):  
Radoje Colovic ◽  
Nikica Grubor ◽  
Vladimir Radak ◽  
Natasa Colovic ◽  
Miodrag Jovanovic ◽  
...  
Keyword(s):  
Blood Vessels ◽  
Good Health ◽  
The Other ◽  
Lethal Outcome ◽  
Necrotising Pancreatitis ◽  
Acute Necrotising Pancreatitis ◽  
Head Of The Pancreas ◽  
Acute Necrotising

Necrosis of the duodenum resulting from acute necrotising pancreatitis is a rare but potentially lethal complication. A small number of cases has been reported so far, the majority of which having, unfortunately, had a lethal outcome. We present the cases of two patients, a 21-year-old woman and a 54- year-old man, both suffering from extensive duodenal necrosis stemming from acute necrotising pancreatitis, and both cases involving the second and third sections of the duodenum, one of which was probably caused by the thrombosis of nutritive blood vessels, the other by an abscess of the head of the pancreas. Due to the extent of the necrosis of the duodenum, there was no option to close so large a hole or to employ any less drastic procedure, so that a complete duodenopancreatectomy had to be performed. One patient survived and has remained in good health for a period of almost ten years, to date. The other patient died six days after surgery due to infection, in spite of an absence of any sort of anastomic complications.

scholarly journals Upregulation of reduced folate carrier by vitamin D enhances brain folate uptake in mice lacking folate receptor alpha

2019 ◽  
Vol 116 (35) ◽  
pp. 17531-17540 ◽  
Author(s):  
Camille Alam ◽  
Susanne Aufreiter ◽  
Constantine J. Georgiou ◽  
Md. Tozammel Hoque ◽  
Richard H. Finnell ◽  
...  
Keyword(s):  
Vitamin D ◽  
Choroid Plexus ◽  
Folate Receptor ◽  
Functional Expression ◽  
Transport Systems ◽  
Reduced Folate Carrier ◽  
Folate Transport ◽  
Folate Receptor Alpha ◽  
Receptor Alpha ◽  
Neurometabolic Disorders

Folates are critical for central nervous system function. Folate transport is mediated by 3 major pathways, reduced folate carrier (RFC), proton-coupled folate transporter (PCFT), and folate receptor alpha (FRα/Folr1), known to be regulated by ligand-activated nuclear receptors. Cerebral folate delivery primarily occurs at the choroid plexus through FRα and PCFT; inactivation of these transport systems can result in very low folate levels in the cerebrospinal fluid causing childhood neurodegenerative disorders. These disorders have devastating effects in young children, and current therapeutic approaches are not sufficiently effective. Our group has previously reported in vitro that functional expression of RFC at the blood–brain barrier (BBB) and its upregulation by the vitamin D nuclear receptor (VDR) could provide an alternative route for brain folate uptake. In this study, we further demonstrated in vivo, using Folr1 knockout (KO) mice, that loss of FRα led to a substantial decrease of folate delivery to the brain and that pretreatment of Folr1 KO mice with the VDR activating ligand, calcitriol (1,25-dihydroxyvitamin D3), resulted in over a 6-fold increase in [13C5]-5-formyltetrahydrofolate ([13C5]-5-formylTHF) concentration in brain tissues, with levels comparable to wild-type animals. Brain-to-plasma concentration ratio of [13C5]-5-formylTHF was also significantly higher in calcitriol-treated Folr1 KO mice (15-fold), indicating a remarkable enhancement in brain folate delivery. These findings demonstrate that augmenting RFC functional expression at the BBB could effectively compensate for the loss of Folr1-mediated folate uptake at the choroid plexus, providing a therapeutic approach for neurometabolic disorders caused by defective brain folate transport.

Seizures with Apnea in Children

PEDIATRICS ◽  
1982 ◽  
Vol 70 (1) ◽  
pp. 87-90
Author(s):  
Kazuyoshi Watanabe ◽  
Kimiko Hara ◽  
Susumu Hakamada ◽  
Tamiko Negoro ◽  
Midori Sugiura ◽  
...  
Keyword(s):  
Limbic System ◽  
Epileptic Seizures ◽  
High Amplitude ◽  
The Other ◽  
Partial Seizures ◽  
Complex Partial Seizures ◽  
Sharp Waves ◽  
Fast Waves ◽  
Respiratory Embarrassment ◽  
Epileptic Fits

Five children who had apneic attacks as a manifestation of epileptic seizures are reported. In three children, the apneic attacks were the sole symptom of epileptic fits. The other two children had additional types of seizures. The apneic seizures usually lasted one to two minutes and were characterized by respiratory embarrassment rather than complete arrest. These seizures are usually accompanied by cyanosis which appears early during the course of the attack. Although consciousness seemed to be impaired, this was difficult to assess accurately in infants. The ictal EEGs disclosed paroxysmal discharges of focal onset in all cases, consisting of high amplitude θ-waves, gradually mixed with or replaced by sharp waves or spikes in some and fast waves followed by slower waves in others. These occurred in temporal areas in three patients and in frontal and central areas in one patient each. Interictal EEGs, however, revealed paroxysmal discharges in only one patient. Apneic attacks in these infants are considered to be an integral part of the manifestations of complex partial seizures originating mostly in the limbic system.

Chemotherapy-induced pyoderma gangrenosum

WCET Journal ◽  
2019 ◽  
pp. 9-17
Author(s):  
Michelle Wai Kuen Lee ◽  
Steven Kar Kay Chan
Keyword(s):  
Pyoderma Gangrenosum ◽  
Systemic Disease ◽  
Skin Lesions ◽  
Skin Condition ◽  
The Other ◽  
Acute Trauma ◽  
Inflammatory Bowel ◽  
Haematological Disorders ◽  
Chronic Myelomonocytic Leukaemia ◽  
Rheumatoid Diseases

Pyoderma gangrenosum (PG) is a refractory, painful, non-infectious, ulcerative and inflammatory skin condition. Approximately 50% of patients with PG showed an existing systemic disease, such as inflammatory bowel conditions, haematological disorders, rheumatoid diseases or hepatopathies. Some patients developed PG following acute trauma or injury in a process known as pathergy. In the other cases, PG is characterised by isolated skin lesions with unknown causes and classified as idiopathic. However, in recent decades, PG has been reported in patients treated with certain medications. In this manuscript, we report two cases of PG, which were triggered by chemotherapy in patients with myelodysplastic syndrome (MDS) and chronic myelomonocytic leukaemia (CMML).

#3079 Investigating the feasibility of automating the differential diagnosis of transient loss of consciousness

2021 ◽  
Vol 92 (8) ◽  
pp. A7.1-A7
Author(s):  
Nathan Pevy ◽  
Heidi Christensen ◽  
Traci Walker ◽  
Markus Reuber
Keyword(s):  
Differential Diagnosis ◽  
Random Forest ◽  
Epileptic Seizures ◽  
The Other ◽  
Future Research ◽  
Loss Of Consciousness ◽  
Transient Loss Of Consciousness ◽  
Audio Recordings ◽  
Transient Loss ◽  
Nonepileptic Seizures

BackgroundThere are three common causes of Transient Loss of Consciousness (TLOC), syncope, epileptic and psychogenic nonepileptic seizures (PNES). Many individuals who have experienced TLOC initially receive an incorrect diagnosis and inappropriate treatment. Whereas syncope can be distinguished from the other two causes relatively easily with a small number of yes/no questions, the differentiation of the other two causes of TLOC is more challenging. Previous qualitative research based on the methodology of Conversation Analysis has demonstrated that epileptic and nonepileptic seizures are described differently when patients talk to clinicians about their TLOC experiences. One particularly prominent difference is that epileptic seizure descriptions are characterised by more formulation effort than accounts of nonepileptic seizures.AimThis research investigates whether features likely to reflect the level of formulation effort can be automatically elicited from audio recordings and transcripts of speech and used to differentiate between epileptic and nonepileptic seizures.MethodVerbatim transcripts of conversations between patients and neurologists were manually produced from video and audio recordings of interactions with 45 patients (21 epilepsy and24 PNES). The subsection of each transcript containing the patients account of their first seizure was manually extracted for the analysis. Seven automatically detectable features were designed as markers of formulation effort. These features were used to train a Random Forest machine learning classifier.ResultsThere were significantly more hesitations and repetitions in descriptions of first epileptic than nonepileptic seizures. Using a nested leave-one-out cross validation approach, 71% of seizures were correctly classified by the Random Forest classifier.ConclusionsThis pilot study provides proof of principle that linguistic features that have been automatically extracted from audio recordings and transcripts could be used to distinguish between epileptic seizures and PNES and thereby contribute to the differential diagnosis of TLOC. Future research should explore whether additional observations can be incorporated into a diagnostic stratification tool. Moreover, future research should explore the performance of these features when they have been extracted from transcripts produced by automatic speech recognition and when they are combined with additional information provided by patients and witnesses about seizure manifestations and medical history.

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