Clinical and molecular spectrum associated with Polymerase-γ related disorders

2022 ◽  
pp. 088307382110670
Author(s):  
Ruchika Jha ◽  
Harshkumar Patel ◽  
Rachana Dubey ◽  
Jyotindra N. Goswami ◽  
Chandana Bhagwat ◽  
...  
Keyword(s):  
Age Of Onset ◽  
Pediatric Population ◽  
Single Gene ◽  
Management Strategies ◽  
Clinical Manifestations ◽  
Progressive External Ophthalmoplegia ◽  
Leigh Disease ◽  
Pathogenic Variants ◽  
Phenotype Analysis

Background POLG pathogenic variants are the commonest single-gene cause of inherited mitochondrial disease. However, the data on clinicogenetic associations in POLG-related disorders are sparse. This study maps the clinicogenetic spectrum of POLG-related disorders in the pediatric population. Methods Individuals were recruited across 6 centers in India. Children diagnosed between January 2015 and August 2020 with pathogenic or likely pathogenic POLG variants and age of onset <15 years were eligible. Phenotypically, patients were categorized into Alpers-Huttenlocher syndrome; myocerebrohepatopathy syndrome; myoclonic epilepsy, myopathy, and sensory ataxia; ataxia-neuropathy spectrum; Leigh disease; and autosomal dominant / recessive progressive external ophthalmoplegia. Results A total of 3729 genetic reports and 4256 hospital records were screened. Twenty-two patients with pathogenic variants were included. Phenotypically, patients were classifiable into Alpers-Huttenlocher syndrome (8/22; 36.4%), progressive external ophthalmoplegia (8/22; 36.4%), Leigh disease (2/22; 9.1%), ataxia-neuropathy spectrum (2/22; 9.1%), and unclassified (2/22; 9.1%). The prominent clinical manifestations included developmental delay (n = 14; 63.7%), neuroregression (n = 14; 63.7%), encephalopathy (n = 11; 50%), epilepsy (n = 11; 50%), ophthalmoplegia (n = 8; 36.4%), and liver dysfunction (n = 8; 36.4%). Forty-four pathogenic variants were identified at 13 loci, and these were clustered at exonuclease (18/44; 40.9%), linker (13/44; 29.5%), polymerase (10/44; 22.7%), and N-terminal domains (3/44; 6.8%). Genotype-phenotype analysis suggested that serious outcomes including neuroregression (odds ratio [OR] 11, 95% CI 2.5, 41), epilepsy (OR 9, 95% CI 2.4, 39), encephalopathy (OR 5.7, 95% CI 1.4, 19), and hepatic dysfunction (OR 4.6, 95% CI 21.3, 15) were associated with at least 1 variant involving linker or polymerase domain. Conclusions We describe the clinical subgroups and their associations with different POLG domains. These can aid in the development of follow-up and management strategies of presymptomatic individuals.

Mucormycosis: Early Identification of a Deadly Fungus

2018 ◽  
Vol 35 (4) ◽  
pp. 257-266
Author(s):  
Ariel M. Brettholz ◽  
Sabrina Opiola Mccauley
Keyword(s):  
Risk Factors ◽  
Patient Outcomes ◽  
Pediatric Oncology ◽  
Clinical Presentation ◽  
Pediatric Population ◽  
Management Strategies ◽  
Clinical Manifestations ◽  
Current Treatment ◽  
Patients With Cancer ◽  
Polymerase Chain

Mucormycosis is a rare invasive fungal infection that affects immunocompromised patients and is fatal when not identified and treated early. Diagnosis is often delayed as the symptoms are nonspecific and frequently mimic other common diseases. Pediatric patients with cancer are at risk for the infection; however, there is limited research that applies directly to the pediatric population. An understanding of the risk factors and clinical presentation of mucormycosis is crucial for the pediatric oncology provider to initiate the workup and provide prompt treatment. The gold standard for diagnosing mucormycosis is biopsy; however, the use of polymerase chain reaction is a novel tool that is being investigated. The mainstays of treatment are antifungal medications, surgery, and reversal of predisposing risk factors, although, new therapies are also emerging. This article will review the pathophysiology, clinical manifestations, and diagnostics of mucormycosis and will discuss current treatment and management strategies for the pediatric oncology clinician to allow for timely diagnosis and intervention to optimize patient outcomes.

scholarly journals Late-onset presentation of POLG1-associated mitochondrial disease

2019 ◽  
Vol 12 (3) ◽  
pp. e228482 ◽  
Author(s):  
Bruna Meira ◽  
Rafael Roque ◽  
Miguel Pinto ◽  
André Caetano
Keyword(s):  
Mitochondrial Disease ◽  
Age Of Onset ◽  
Late Onset ◽  
Clinical Manifestations ◽  
Progressive External Ophthalmoplegia ◽  
Clinical Feature ◽  
Gait Ataxia ◽  
Chronic Progressive External Ophthalmoplegia ◽  
Genetic Studies ◽  
In Cis

Mutations in the nuclear POLG1 gene compromise the integrity of mitochondrial DNA and show great allelic and clinical heterogeneity. Among adult POLG1-associated mitochondrial disease, the main clinical feature is chronic progressive external ophthalmoplegia. Other related clinical manifestations are sensory or cerebellar ataxia, peripheral neuropathy, myopathy or extrapyramidal symptoms. We report the case of a 72-year-old man who presented with a late onset sensory neuronopathy, chronic progressive external ophthalmoplegia, gait ataxia and parkinsonism. Genetic studies showed a compound heterozygosity of known pathogenic mutations in the POLG1 gene (variant T252I/P587 L in cis configuration in allele 1 and variant R807C in allele 2). Late life presentation highlights that mitochondrial disorders should be considered regardless of age of onset of symptoms.

scholarly journals Umbilical hernia in children

2003 ◽  
Vol 56 (5-6) ◽  
pp. 291-294 ◽  
Author(s):  
Smiljana Marinkovic ◽  
Svetlana Bukarica
Keyword(s):  
Umbilical Hernia ◽  
Pain Treatment ◽  
Pediatric Population ◽  
Treatment Options ◽  
Clinical Manifestations ◽  
Great Majority ◽  
Common Condition ◽  
Direct Hernia ◽  
Incomplete Closure

Introduction Umbilical hernia is a common condition in the pediatric population. Embryology Umbilical hernia is a consequence of incomplete closure or weakness at the umbilical ring, where protrusion of intraabdominal contents may occur. Anatomy Fascia posterior to the canal is thinner creating an area of weakness. Congenital or direct hernia occurs in this area, while herniation in the umbilical canal leads to indirect or acquired hernia. Incidence The incidence of umbilical hernia is 1.9% to l8.5% in white population. Clinical manifestations The great majority of pediatric umbilical hernias are asymptomatic. Incarceration and strangulation are uncommon Rupture of umbilical hernia with resultant evisceration is extremely rare Umbilical hernia may also be the source of intermittent umbilical or abdominal pain. Treatment Treatment options for umbilical hernias range from simple observation to surgical repair. The great majority close spontaneously and observation with periodic follow-up is appropriate in most cases. There are no available data to suggest that strapping improves or accelerates closure. Operation would be recommended for defects greater than 1cm, by the age 3 to 4. Persistence or enlargement of fascial defect during the period of observation are reasons to consider repair, whatever the age. Complications Complications of operative repair of umbilical hernias include those related to anesthesia and local wound infections. Conclusion Umbilical hernia is a common condition among infants and children. In the great majority of cases the natural history is one of eventual closure without treatment. If spontaneous closure does not occur until the age of 3-4 years, operative correction is recommended.

Inferior Turbinectomy in Children

2003 ◽  
Vol 17 (2) ◽  
pp. 69-73 ◽  
Author(s):  
Samuel Segal ◽  
Ephraim Eviatar ◽  
Leonard Berenholz ◽  
Alex Kessler ◽  
Nathan Shlamkovitch ◽  
...  
Keyword(s):  
Sleep Apnea ◽  
Postoperative Complications ◽  
Nasal Obstruction ◽  
Pediatric Population ◽  
Clinical Manifestations ◽  
Older Children ◽  
Nasal Breathing ◽  
History Of ◽  
Nasal Secretions

Background Inferior turbinectomy on patients of all ages is a controversial procedure. Its effect on children has been reported little in the literature and the few studies that are available involved relatively older children, i.e., >10 years old. Nasal obstruction caused by extensive hypertrophy of the inferior turbinates is not an uncommon observation in the pediatric population. The clinical manifestations might present as snoring, noisy breathing, mouth breathing, and, possibly, sleep apnea. Methods In this study, we followed 227 children >10 years of age who underwent inferior turbinectomy (27 children also underwent a revision of an earlier adenoidectomy), of whom 179 children had significant relief of nasal obstruction at the 1-year follow-up. Results Nocturnal breathing was reported to be more regular and otherwise improved in the 36 children with a suspected history of sleep apnea. Forty-two of 47 children who had thick nasal secretions and did not respond to antibiotic therapy before the operation had significant relief postoperatively. Postoperative complications were few and their number did not exceed that of adults. Conclusions A complete inferior turbinectomy should be considered in children >10 years of age who have hypertrophied inferior turbinates that cause major interference with nasal breathing.

scholarly journals Laryngeal Rosai-Dorfman Disease (Sinus Histiocytosis with Massive Lymphadenopathy): A Retrospective Study of 5 Cases

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Yanyan Niu ◽  
Yongjin Li ◽  
Jian Wang ◽  
Xiaofeng Jin ◽  
Dahai Yang ◽  
...  
Keyword(s):  
Surgical Resection ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Hormone Treatment ◽  
Good Prognosis ◽  
Massive Lymphadenopathy ◽  
Rosai Dorfman Disease ◽  
Alive With Disease ◽  
Laryngeal Involvement

This study was performed to investigate the clinical manifestations, treatment methods, and prognosis of Rosai-Dorfman disease (RDD) with laryngeal involvement. Five clinical cases of RDD with laryngeal involvement diagnosed between 1986 and 2015 were retrospectively analyzed. The laryngeal lesions of these 5 patients mostly involved the glottis and subglottis, with the main symptoms being a hoarse voice and airway obstruction. In addition, the patients mostly exhibited a unilateral or asymmetric onset that was manifested by a laryngeal submucosal nodular mass. The patients were subjected to a regimen of hormone treatment combined with surgical resection. The median follow-up duration was 101 months (8–384 months). One case was lost, and the remaining 4 subjects are alive with disease. The follow-up examinations revealed that 4 subjects had stable laryngeal conditions, whereas one showed minor progression. RDD with laryngeal involvement is clinically rare and differs considerably from classical RDD in age of onset, gender composition, and extranodal involvement. The regimen of hormone treatment combined with surgical resection can stabilize the patient’s general condition and laryngeal lesion. Tracheotomies are recommended for patients with dyspnea. After their conditions stabilize, decannulation can be successfully performed in most cases. This therapeutic regimen generally delivers a good prognosis.

scholarly journals Malignant clinical course of mycotic intracranial aneurysms in children: A review

2020 ◽  
Vol 11 ◽  
pp. 71
Author(s):  
Yahya H Khormi ◽  
Ronette Goodluck Tyndall ◽  
Mandeep Tamber
Keyword(s):  
Clinical Course ◽  
Pediatric Population ◽  
Management Strategies ◽  
Sudden Onset ◽  
New Right ◽  
Unruptured Aneurysms ◽  
History Of ◽  
Mycotic Aneurysms ◽  
Imminent Risk

Background: Mycotic aneurysms are a rare in the pediatric population. The natural history of these lesions and their appropriate management strategies is controversial. Case Description: A 13-year-old male presented with the sudden onset of a headache, vomiting, and fever. Inflammatory markers were elevated, and the blood culture was positive for Streptococcus viridans. When the computed tomography angiography (CTA) showed a ruptured mycotic aneurysm accompanied by multiple small unruptured aneurysms, he was started on antibiotics and underwent an urgent craniotomy. Despite negative blood cultures, the follow-up CTA showed further enlargement of the previously diagnosed aneurysms and a new right frontal aneurysm. The second and third craniotomies were, respectively, performed to resect the additional aneurysms. Pathologically, both aneurysmal walls were markedly inflamed and attenuated, suggesting the imminent risk of aneurysmal rupture. Following the total of three craniotomies, the patient had an uneventful postoperative course. Within 2 weeks, he regained baseline neurological function. Conclusion: Mycotic aneurysms in children may follow a very malignant course. Aneurysms may grow, new ones may form, and repeated CTAs are required to direct further follow-up treatment.

scholarly journals Quando hipertensão arterial persistente no adolescente tem uma origem endócrina rara: relato de dois casos e revisão da literatura

2017 ◽  
Vol 27 (3) ◽  
pp. 26960
Author(s):  
Clara Gomes ◽  
Gabriela Laranjo ◽  
Elisabete Santos ◽  
Cristina Faria
Keyword(s):  
Blood Pressure ◽  
Clinical Presentation ◽  
Pediatric Population ◽  
Clinical Manifestations ◽  
Pathological Examination ◽  
Left Adrenal Gland ◽  
Ultrasound Computed Tomography ◽  
Lower Morbidity

*** When persistent hypertension  in adolescents has a rare endocrine etiology: report of two cases and literature review ***AIMS: To report two clinical cases of pheochromocytoma, a rare tumor in the pediatric population, that affects the adrenal medulla, is malignant in up to 47% of cases,  and whose clinical manifestations result from hypersecretion of catecholamines.CASE DESCRIPTION: Two cases of pheochromocytoma in adolescents are described, both with persistent hypertension and one with headache, sweating, and tachycardia. Renal and adrenal ultrasound, computed tomography angiography, and measurements of catecholamines and their metabolites revealed pheochromocytoma in the left adrenal gland. Adrenalectomy was performed after pretreatment with α-blockers. Pathological examination confirmed the diagnosis. Blood pressure returned to normal in both patients after treatment.CONCLUSIONS: Pheochromocytoma has a varied and nonspecific clinical presentation, but this condition should always be considered in the differential diagnosis of high blood pressure. Early diagnosis may imply a less aggressive treatment, lower morbidity, and a lesser impact on patients’ quality of life. The high likelihood of recurrence of pheochromocytoma, including as metastatic disease, requires follow-up visits for several years after its initial clinical presentation, even in the case of an apparent cure.

scholarly journals Idiopathic CRMO and MEFV Gene Variant Alleles: Is There Any Relationship?

2019 ◽  
Vol 2019 ◽  
pp. 1-4
Author(s):  
Farhad Salehzadeh ◽  
Hassan Anari ◽  
Sepehr Sarkhanloo
Keyword(s):  
Age Of Onset ◽  
Mefv Gene ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Bone Lesions ◽  
Gene Variant ◽  
Intermittent Fever ◽  
Pathogenic Variants ◽  
Long Duration ◽  
Variant Alleles

Background and Objective. CRMO is an inflammatory disease of bone that occurs more often in children. The clinical manifestations are intermittent fever, pain, and bone lesions, especially in long bones. Although there is an idiopathic type of disease, it is usually associated with some autoimmune disorders. This study evaluates MEFV gene mutations as background pathology of idiopathic CRMO. Methods. Blood samples of patients, who diagnosed as childhood idiopathic CRMO by imaging and pathologic study from June 2011 until September 2018, have been screened for the 12 common pathogenic variants of MEFV gene mutations. Result. Nine patients enrolled in this study, and eight of them were male. The most common involvement locations were tibia and femur, and the least ones were zygoma, calcaneus, and radius. The mean duration of the involvement was 1.3 years. Six patients had only 1 involved location, 2 patients showed two sites of involvement, and one patient had three affected areas. There were two positive MEFV gene mutations (22%), as E148Q/wt and K695R/wt both in the heterozygote form. There was no meaningful relationship between MEFV gene mutations and the age of onset, gender, and location of involvement. Patients with positive mutation had more involved sites and long duration of involvement significantly. Conclusion. There is no significant immunopathogenic relationship between the common MEFV gene variant alleles and CRMO disease.

scholarly journals The Effect of Amino Acid, Carbohydrate, and Lipid Metabolism Disorders on Eyes

2020 ◽  
Vol 6 (3) ◽  
pp. 190-196
Author(s):  
Abdolreza Medghalchi ◽  
Keyword(s):  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Age Of Onset ◽  
Genetic Disorders ◽  
Clinical Manifestations ◽  
Final Diagnosis ◽  
Lipid Metabolism Disorders ◽  
Inherited Metabolic Disorders ◽  
Ophthalmological Assessment

Inherited metabolic disorders (IMDs) are a class of genetic disorders. Each metabolic disorder may have different forms with different age of onset, clinical manifestations, severity, and even type of inheritance. Ideally, a group of different specialists, including ophthalmologists, pediatricians, biochemists, and medical geneticists are needed for the final diagnosis and management of IMDs. Because of the importance of the aforementioned issue, we investigated the effect of IMDs on the eye in this review. Metabolic disorders can induce abnormalities in conjunctiva, cornea, lens, retina, optic nerve, and eye motility.  In this study, the authors aimed to address the effect of metabolic diseases of amino acids, carbohydrates, and lipids on eye metabolism. Because of the direct toxic mechanisms of abnormal metabolites on the eyes and regarding the effect of eye monitoring on follow-up, management, and treatment of IMDs, a detailed ophthalmological assessment is essential.

A glance on dystonias, how to recognize and handle them

2019 ◽  
pp. 22-29
Author(s):  
F. N. Mercan ◽  
E. Bayram ◽  
M. C. Akbostanci
Keyword(s):  
Differential Diagnosis ◽  
Movement Disorder ◽  
Age Of Onset ◽  
Clinical Manifestations ◽  
Body Part ◽  
Classification Model ◽  
Treatment Choices ◽  
Muscle Groups

Dystonia refers to an involuntary, repetitive, sustained, painful and twisting movements of the affected body part. This movement disorder was first described in 1911 by Hermain Oppenheim, and many studies have been conducted to understand the mechanism, the diagnosis and the treatment of dystonia ever since. However, there are still many unexplained aspects of this phenomenon. Dystonia is diagnosed by clinical manifestations, and various classifications are recommended for the diagnosis and the treatment. Anatomic classification, which is based on the muscle groups involved, is the most helpful classification model to plan the course of the treatment. Dystonias can also be classified based on the age of onset and the cause. These dystonic syndromes can be present without an identified etiology or they can be clinical manifestations of a neurodegenerative or neurometabolic disease. In this review we summarized the differential diagnosis, definition, classifications, possible mechanisms and treatment choices of dystonia.

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