Diagnosis of 'possible' mitochondrial disease: an existential crisis.
clinical genetics; diagnosis; evidence based practice; metabolic disorders
Primary genetic mitochondrial diseases are often difficult to diagnose, and the term 'possible' mitochondrial disease is used frequently by clinicians when such a diagnosis is suspected. There are now many known phenocopies of mitochondrial disease. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting mitochondrial disease may have other genetic disorders. In instances when a genetic diagnosis cannot be confirmed, a diagnosis of 'possible' mitochondrial disease may result in harm to patients and their families, creating anxiety, delaying appropriate diagnosis and leading to inappropriate management or care. A categorisation of 'diagnosis uncertain', together with a specific description of the metabolic or genetic abnormalities identified, is preferred when a mitochondrial disease cannot be genetically confirmed.
Parikh Sumit; Karaa Amel; Goldstein Amy; Bertini Enrico Silvio; Chinnery Patrick F; Christodoulou John; Cohen Bruce H; Davis Ryan L; Falk Marni J; Fratter Carl; Horvath Rita; Koenig Mary Kay; Mancuso Michaelangelo; McCormack Shana; McCormick Elizabeth M; McFarland Robert; Nesbitt Victoria; Schiff Manuel; Steele Hannah; Stockler Silvia; Sue Carolyn; Tarnopolsky Mark; Thorburn David R; Vockley Jerry; Rahman Shamima
Journal of medical genetics
2019
2019-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.1136/jmedgenet-2018-105800" target="_blank" rel="noreferrer noopener">10.1136/jmedgenet-2018-105800</a>
Diagnosis of 'possible' mitochondrial disease: an existential crisis.
clinical genetics; diagnosis; evidence based practice; metabolic disorders
Primary genetic mitochondrial diseases are often difficult to diagnose, and the term 'possible' mitochondrial disease is used frequently by clinicians when such a diagnosis is suspected. There are now many known phenocopies of mitochondrial disease. Advances in genomic testing have shown that some patients with a clinical phenotype and biochemical abnormalities suggesting mitochondrial disease may have other genetic disorders. In instances when a genetic diagnosis cannot be confirmed, a diagnosis of 'possible' mitochondrial disease may result in harm to patients and their families, creating anxiety, delaying appropriate diagnosis and leading to inappropriate management or care. A categorisation of 'diagnosis uncertain', together with a specific description of the metabolic or genetic abnormalities identified, is preferred when a mitochondrial disease cannot be genetically confirmed.
Parikh Sumit; Karaa Amel; Goldstein Amy; Bertini Enrico Silvio; Chinnery Patrick F; Christodoulou John; Cohen Bruce H; Davis Ryan L; Falk Marni J; Fratter Carl; Horvath Rita; Koenig Mary Kay; Mancuso Michaelangelo; McCormack Shana; McCormick Elizabeth M; McFarland Robert; Nesbitt Victoria; Schiff Manuel; Steele Hannah; Stockler Silvia; Sue Carolyn; Tarnopolsky Mark; Thorburn David R; Vockley Jerry; Rahman Shamima
Journal of medical genetics
2019
2019-03
<a href="http://doi.org/10.1136/jmedgenet-2018-105800" target="_blank" rel="noreferrer noopener">10.1136/jmedgenet-2018-105800</a>
Adolescents with urinary stones have elevated urine levels of inflammatory mediators
Biomarker; Cytokine; Innate immunity; Interleukin
Urinary stones are increasing in children, primarily during adolescence. Although urinary stones are often viewed in the context of intermittent stone events, increasing evidence indicates that stones are a metabolic process associated with chronic kidney disease and cardiovascular disease. These aforementioned stone-associated conditions may have pediatric origins. To compare urine inflammatory markers in otherwise healthy stone forming children versus matched controls. Urine samples were collected from 12 adolescents with urinary stones along with 15 controls. The levels of 30 urine cytokines were measured using a Mesoscale 30-Plex Human Cytokine panel and normalized to urine creatinine levels. Macrophage inflammatory protein 1β and interleukin 13 levels were significantly elevated in the urine of the stone forming adolescents compared to controls. Interleukin 17A was elevated in the urine of controls. This study indicates that urine levels of cytokines involved in chronic inflammation and fibrosis are elevated in urinary stone formers as early as adolescence. Because stone formers are at risk for chronic kidney disease, macrophage inflammatory protein 1β and interleukin 13 represent investigative targets.
Kusumi Kirsten; Ketz John; Saxena Vijay; Spencer John David; Safadi Fayez; Schwaderer Andrew
Urolithiasis
2019
2019-04
<a href="http://doi.org/10.1007/s00240-019-01133-1" target="_blank" rel="noreferrer noopener">10.1007/s00240-019-01133-1</a>
Exercise-Induced Dyspnea in Children and Adolescents: Differential Diagnosis
Pediatrics; adults; asthma; induced bronchoconstriction; hyperventilation; vocal-cord dysfunction
Exercise-induced dyspnea in children and adolescents can occur for many reasons. Although asthma is the common cause, failure to prevent exercise-induced asthma by pretreatment with a bronchodilator, such as albuterol, indicates that other etiologies should be considered. Other causes of exercise-induced dyspnea include exercise-induced vocal cord dysfunction, exercise-induced laryngomalacia, exercise-induced hyperventilation, chest wall restrictive abnormalities, cardiac causes, and normal physiologic limitation. When exercise-induced dyspnea is not from asthma, cardiopulmonary exercise testing with reproduction of the patient's dyspnea is the means to identify the other causes. Cardiopulmonary exercise testing monitors oxygen use, carbon-dioxide production, end-tidal pCO(2) (partial pressure of carbon dioxide), and electrocardiogram. Additional components to testing are measurement of blood pH and pCO(2) when symptoms are reproduced, and selective flexible laryngoscopy when upper airway obstruction is observed to specifically identify vocal cord dysfunction or laryngomalacia. This approach is a highly effective means to identify exercise-induced dyspnea that is not caused by asthma.
Bhatia R; Abu-Hasan M; Weinberger M
Pediatric Annals
2019
2019-03
Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).
<a href="http://doi.org/10.3928/19382359-20190219-02" target="_blank" rel="noreferrer noopener">10.3928/19382359-20190219-02</a>
Emergent high fatality lung disease in systemic juvenile arthritis
treatment; inflammation; adult onset still's disease; DMARDs (biologic); juvenile idiopathic arthritis
OBJECTIVE: To investigate the characteristics and risk factors of a novel parenchymal lung disease (LD), increasingly detected in systemic juvenile idiopathic arthritis (sJIA). METHODS: In a multicentre retrospective study, 61 cases were investigated using physician-reported clinical information and centralised analyses of radiological, pathological and genetic data. RESULTS: LD was associated with distinctive features, including acute erythematous clubbing and a high frequency of anaphylactic reactions to the interleukin (IL)-6 inhibitor, tocilizumab. Serum ferritin elevation and/or significant lymphopaenia preceded LD detection. The most prevalent chest CT pattern was septal thickening, involving the periphery of multiple lobes ± ground-glass opacities. The predominant pathology (23 of 36) was pulmonary alveolar proteinosis and/or endogenous lipoid pneumonia (PAP/ELP), with atypical features including regional involvement and concomitant vascular changes. Apparent severe delayed drug hypersensitivity occurred in some cases. The 5-year survival was 42%. Whole exome sequencing (20 of 61) did not identify a novel monogenic defect or likely causal PAP-related or macrophage activation syndrome (MAS)-related mutations. Trisomy 21 and young sJIA onset increased LD risk. Exposure to IL-1 and IL-6 inhibitors (46 of 61) was associated with multiple LD features. By several indicators, severity of sJIA was comparable in drug-exposed subjects and published sJIA cohorts. MAS at sJIA onset was increased in the drug-exposed, but was not associated with LD features. CONCLUSIONS: A rare, life-threatening lung disease in sJIA is defined by a constellation of unusual clinical characteristics. The pathology, a PAP/ELP variant, suggests macrophage dysfunction. Inhibitor exposure may promote LD, independent of sJIA severity, in a small subset of treated patients. Treatment/prevention strategies are needed.
Saper Vivian E; Chen Guangbo; Deutsch Gail H; Guillerman R Paul; Birgmeier Johannes; Jagadeesh Karthik; Canna Scott; Schulert Grant; Deterding Robin; Xu Jianpeng; Leung Ann N; Bouzoubaa Layla; Abulaban Khalid; Baszis Kevin; Behrens Edward M; Birmingham James; Casey Alicia; Cidon Michal; Cron Randy Q; De Aliva; De Benedetti Fabrizio; Ferguson Ian; Fishman Martha P; Goodman Steven I; Graham T Brent; Grom Alexei A; Haines Kathleen; Hazen Melissa; Henderson Lauren A; Ho Assunta; Ibarra Maria; Inman Christi J; Jerath Rita; Khawaja Khulood; Kingsbury Daniel J; Klein-Gitelman Marisa; Lai Khanh; Lapidus Sivia; Lin Clara; Lin Jenny; Liptzin Deborah R; Milojevic Diana; Mombourquette Joy; Onel Karen; Ozen Seza; Perez Maria; Phillippi Kathryn; Prahalad Sampath; Radhakrishna Suhas; Reinhardt Adam; Riskalla Mona; Rosenwasser Natalie; Roth Johannes; Schneider Rayfel; Schonenberg-Meinema Dieneke; Shenoi Susan; Smith Judith A; Sönmez Hafize Emine; Stoll Matthew L; Towe Christopher; Vargas Sara O; Vehe Richard K; Young Lisa R; Yang Jacqueline; Desai Tushar; Balise Raymond; Lu Ying; Tian Lu; Bejerano Gill; Davis Mark M; Khatri Purvesh; Mellins Elizabeth D; Childhood Arthritis and Rheumatology Research Alliance Registry Investigators
Annals Of The Rheumatic Diseases
2019
2019-12
Journal Article
<a href="http://doi.org/10.1136/annrheumdis-2019-216040" target="_blank" rel="noreferrer noopener">10.1136/annrheumdis-2019-216040</a>
PMID: 31562126
Pediatric Migraine Action Plan (PedMAP)
Turner Scott B; Rende Elizabeth K; Pezzuto Tara; Weaver Samantha; Henderlong-Kropp Annmarie; Greene Kaitlin A; Bicknese Alma R; Dilts Jennifer J; Gautreaux Jennifer; Victorio M Cristina C; Strauss Lauren D; Lagman-Bartolome Ana Marissa; Szperka Christina L; Yonker Marcy; Hershey Andrew D; Gelfand Amy A
Headache
2019
2019-11
Journal Article
<a href="http://doi.org/10.1111/head.13681" target="_blank" rel="noreferrer noopener">10.1111/head.13681</a>
PMID: 31710105
Ugh
Pediatrics; Mental health; Medicine; Social Work; Medicine & Public Health; Health Psychology; Medical Sociology; Premedical Education; Family support
Ugh. I am ashamed to say that is the first word that comes to my mind when I see Jake’s name on my schedule for the day. He is 10 and he has been my patient since he was born. He has an 8-year-old sister Annie and a 5-year-old brother Jimmy. They usually all come in together with their mother even if only one of them has an appointment that day.
Sladjana Courson
Health Disparities : Weaving A New Understanding Through Case Narratives
2019
2019
Journal Article
<a href="http://doi.org/10.1007/978-3-030-12771-8_46" target="_blank" rel="noreferrer noopener">10.1007/978-3-030-12771-8_46</a>
Chemotherapy Strategies for Young Children Newly-Diagnosed with Medulloblastoma up to the Era of Molecular Profiling - A Comparative Outcomes Analysis
Finlay J; Mynarek M; Dhall G; Lafay-Cousin L; Mazewski C M; Ashley D; Cohen B H; von Bueren A O; Gerber N; Leary S; Geyer J R; Tait D; Gajjar A; Rutkowski S
Pediatric Blood & Cancer
2019
2019-12
Journal Article
<a href="http://doi.org/10.1093/neuonc/noz175.767" target="_blank" rel="noreferrer noopener">10.1093/neuonc/noz175.767</a>