HTRA2 Defect: A Recognizable Inborn Error of Metabolism with 3-Methylglutaconic Aciduria as Discriminating Feature Characterized by Neonatal Movement Disorder and Epilepsy—Report of 11 Patients

2018 ◽  
Vol 49 (06) ◽  
pp. 373-378 ◽  
Author(s):  
Gilles Morin ◽  
Maria Nouri ◽  
Oliver Brandau ◽  
Nebal Saadi ◽  
Mohammed Nouri ◽  
...  
Keyword(s):  
Inborn Error ◽  
Mitochondrial Membrane ◽  
Clinical Characteristics ◽  
Mitochondrial Disorders ◽  
Clinical Findings ◽  
Urinary Organic Acid ◽  
Inborn Errors ◽  
Neonatal Onset ◽  
Urinary Organic Acid Analysis ◽  
Methylglutaconic Aciduria

AbstractNeonatal-onset movement disorders, especially in combination with seizures, are rare and often related to mitochondrial disorders. 3-methylglutaconic aciduria (3-MGA-uria) is a marker for mitochondrial dysfunction. In particular, consistently elevated urinary excretion of 3-methylglutaconic acid is the hallmark of a small but growing group of inborn errors of metabolism (IEM) due to defective phospholipid remodeling or mitochondrial membrane-associated disorders (mutations in TAZ, SERAC1, OPA3, CLPB, DNAJC19, TMEM70, TIMM50). Exome/genome sequencing is a powerful tool for the diagnosis of the clinically and genetically heterogeneous mitochondrial disorders. Here, we report 11 individuals, of whom 2 are previously unpublished, with biallelic variants in high temperature requirement protein A2 (HTRA2) encoding a mitochondria-localized serine protease. All individuals presented a recognizable phenotype with neonatal- or infantile-onset neurodegeneration and death within the first month of life. Hallmark features were central hypopnea/apnea leading to respiratory insufficiency, seizures, neutropenia, 3-MGA-uria, tonus dysregulation, and dysphagia. Tremor, jitteriness, dystonia, and/or clonus were also common. HTRA2 defect should be grouped under the IEM with 3-MGA-uria as discriminating feature. Clinical characteristics overlap with other disorders of this group suggesting a common underlying pathomechanism. Urinary organic acid analysis is a noninvasive and inexpensive test that can guide further genetic testing in children with suggestive clinical findings.

Molybdenum Cofactor Deficiency: Another Inborn Error of Metabolism With Neonatal Onset

PEDIATRICS ◽  
1988 ◽  
Vol 82 (3) ◽  
pp. 521-521
Author(s):  
MASAFUMI MATSUO ◽  
EISAKU MAEDA ◽  
HAJIME NAKAMURA ◽  
KAYOKO SAIKI
Keyword(s):  
Inborn Error ◽  
Inborn Errors Of Metabolism ◽  
Early Recognition ◽  
Case Reports ◽  
Molybdenum Cofactor ◽  
Inborn Errors ◽  
Molybdenum Cofactor Deficiency ◽  
Neonatal Onset ◽  
Proper Diagnosis ◽  
Cofactor Deficiency

To the Editor.— We agree with Dr Burton1 that the practicing physician has the responsibility for the initial recognition of inborn errors of metabolism. Because we have experienced many cases of inborn errors of metabolism in neonates who might have died soon after birth without a proper diagnosis, we advocate that every neonatologist has the responsibility of recognizing these disorders. To promote the early recognition, we must know the initial signs or symptoms of neonatal cases of inborn errors of metabolism and we have collected neonatal case reports in the literatures during the last 5 years.

A rare progressive neurometabolic disease (L-2-hydroxyglutaric aciduria) diagnosed by urinary organic acid analysis

2006 ◽  
Vol 37 (03) ◽  
Author(s):  
S Vlaho ◽  
S Posselt ◽  
V Boda ◽  
M Baz Bartels ◽  
S Parbel ◽  
...  
Keyword(s):  
Organic Acid ◽  
Urinary Organic Acid ◽  
Organic Acid Analysis ◽  
Urinary Organic Acid Analysis

Neonatal-Onset Familial Mediterranean Fever in an Infant with Human Parainfluenza Virus-4 Infection

Neonatology ◽  
2021 ◽  
pp. 1-5
Author(s):  
Alexandre Michev ◽  
Alessandro Borghesi ◽  
Caterina Tretti ◽  
Maddalena Martella ◽  
Amelia Di Comite ◽  
...  
Keyword(s):  
Familial Mediterranean Fever ◽  
Parainfluenza Virus ◽  
Compound Heterozygous ◽  
Inborn Errors ◽  
Immunological Responses ◽  
Inflammatory Conditions ◽  
Neonatal Onset ◽  
Mediterranean Fever ◽  
Compound Heterozygous Variants ◽  
Human Parainfluenza Virus

Unusual, severe infections or inflammatory episodes in newborns and infants are largely unexplained and often attributed to immature immune responses. Inborn errors of immunity (IEI) are increasingly recognized as the etiology of life-threatening inflammatory and infectious diseases in infancy. We describe a patient with a unique neonatal-onset Familial Mediterranean Fever (FMF) due to compound heterozygous variants in <i>MEFV</i>, presenting as pleuritis following human parainfluenza virus-4 infection. Diagnostic challenges of FMF in infancy include the interpretation of the attacks as infectious episodes. Newborns and infants with acute, recurrent, or chronic, unusually severe infectious or inflammatory conditions should be screened for IEI, including both disorders with defective immunological responses and autoinflammatory disorders.

Inborn Errors of Metabolism

1980 ◽  
Vol 2 (6) ◽  
pp. 175-181
Author(s):  
George M. Komrower
Keyword(s):  
Neurospora Crassa ◽  
Inborn Error ◽  
Inborn Errors Of Metabolism ◽  
Metabolic Disorders ◽  
Homogentisic Acid ◽  
Turn Of The Century ◽  
Inborn Errors ◽  
The Family ◽  
The One ◽  
Biochemical Abnormalities

Around the turn of the century Garrard established the concept of an inborn error of metabolism using his study on alcaptonuria to exemplify his hypothesis that a considerable number of metabolic disorders with clearly defined clinical, pathologic, and biochemical abnormalities arise because an enzyme governing a single metabolic step is either reduced in activity or missing altogether. He pointed out the familial distribution of alcaptonuria and later showed that the inheritance could be explained on mendelian principles, ie, the affected individual was homozygous for the abnormal gene and that the inheritance was recessive, both parents being heterozygous for the disorder. He suggested that the accumulation of homogentisic acid in alcaptonuria was evidence that this substance is a normal metabolite in the degradation of tyrosine and attributed this accumulation to a failure of oxidation of homogentisic acid. In addition to alcaptonuria he described cystinunia, pentosuria, and albinism. This work was the forerunner of the classic studies of Beadle and Tatum on mutants of Neurospora crassa which led to the one gene-one enzyme concept. DETECTION Different groups require special attention: the family at risk because of previously affected individuals, those with unusual features suggestive of metabolic disorders, and sick newborns. Screening of normal newborns requires a different approach.

scholarly journals Ewing sarcoma: Analysis of epidemiological parameters and their relation to clinical characteristics

2006 ◽  
Vol 134 (7-8) ◽  
pp. 310-314
Author(s):  
Vladan Stevanovic ◽  
Zoran Vukasinovic ◽  
Dusko Spasovski
Keyword(s):  
Ewing Sarcoma ◽  
Orthopedic Surgery ◽  
Clinical Characteristics ◽  
Clinical Findings ◽  
Tumor Localization ◽  
Age Group ◽  
Serious Illness ◽  
Success Of Treatment ◽  
Epidemiologic Features ◽  
Epidemiological Parameters

The purpose of this investigation was to evaluate epidemiologic features of Ewing sarcoma in children treated in the Institute for Orthopedic Surgery "Banjica", as well as to establish relation of these features to clinical findings. Study involved 78 patients treated over 20-year period (1980-2000). Analysis included standard epidemiologic data (age, sex, tumor localization) and diagnostic clinical features on presentation (major symptoms, time elapsed between presentation and diagnosis, presence of metastases). Most of the patients were in the age group of 15-18 years (50.0%), predominantly males. In general, the results of our study were consistent with data reported in literature. Nevertheless, this investigation revealed slightly higher incidence in patients younger than four years of age (5.1%); localization on the upper extremity was found to be more frequent (upper to lower extremity ratio was nearly 3:1 in our study), and the time lost between presentation and diagnosis was markedly reduced (average time elapsed between presentation and diagnosis was 2.5 months). The results of our study may improve efficiency and success of treatment, thus providing the basis of better prognosis in management of such a serious illness.

scholarly journals Pathways and Inborn Errors of Bile Acid Synthesis

Acta Medica ◽  
2019 ◽  
Vol 50 (4) ◽  
pp. 48-56
Author(s):  
Ufuk Bozkurt Obuz ◽  
Incilay Lay
Keyword(s):  
Bile Acid ◽  
Early Diagnosis ◽  
Bile Acids ◽  
Biosynthetic Pathway ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Clinical Findings ◽  
Inborn Errors ◽  
Genes Encoding ◽  
Intracellular Compartments

Bile acids are synthesized from cholesterol through 17 different enzymes located in different intracellular compartments of hepatocytes. Defects have been identified in the genes encoding the enzymes involved in the bile acid synthesis pathways and nine different diseases have been identified so far. In this review, four different biosynthetic pathway of bile acids together with disorders of bile acid synthesis is described. In inborn errors of bile acid synthesis clinical findings can range from liver failure to cirrhosis in infancy or progressive neuropathy in adolescence / adulthood. Laboratory analysis of urine profiling of bile acids is important in early diagnosis and early treatment.

scholarly journals Acute bacterial nephritis. A descriptive study of an underdiagnosed entity

2020 ◽  
Vol 80 (3) ◽  
pp. 1-10
Author(s):  
Pedro Antonio Madero-Morales ◽  
Rigoberto Pallares-Méndez ◽  
Rodrigo Romero-Mata ◽  
Guillermo Vizcarra-Mata ◽  
Andrés Guillén-Lozoya
Keyword(s):  
Acute Pyelonephritis ◽  
Clinical Characteristics ◽  
Clinical Course ◽  
Case Series ◽  
Therapy Response ◽  
Time Frame ◽  
Clinical Findings ◽  
Imaging Features ◽  
Imaging Studies ◽  
Retrospective Case

Background: Acute bacterial nephritis is an infectious process diagnosed through imaging studies. The clinical course of the disease has been shown to be more aggressive than acute pyelonephritis. It continues to be underdiagnosed, thus there are few studies on the entity in the literature. Objective: To describe the clinical characteristics and imaging features of acute bacterial nephritis, as well as its clinical course. Design: A descriptive, retrospective case series was conducted. Materials and methods: Thirty-two cases of acute bacterial nephritis in patients admitted to the hospital within the time frame of 2009 to 2016 were reviewed. The patients’ clinical characteristics upon admission were registered, as well as inpatient clinical progression, culture results, and antibiotic therapy response. The imaging studies were re-evaluated and the diagnostic consistency with either the focal or multifocal disease presentation was confirmed. Results: Cases predominated in women (n=29, 90.62%) and the most frequently associated comorbidities were diabetes (n=16, 50%) and obesity (n=9, 28.25%). The most important clinical findings upon admission were fever (n=15, 46.87%) and leukocytosis (n=27, 84.38%). Escherichia coli was the most commonly isolated bacterium (63.63%). Both acute focal bacterial nephritis and acute multifocal bacterial nephritis were observed in 46.87% (n=15) and 53.13% (n=17) of the patients, respectively. Imaging studies were required for all diagnoses. Conclusion: Fever and leukocytosis are the main findings in acute bacterial nephritis. Imaging studies are necessary for making the diagnosis, given that acute pyelonephritis and acute bacterial nephritis cannot be clinically differentiated.

scholarly journals A young adult with COVID-19 and multisystem inflammatory syndrome in children (MIS-C)-like illness: a case report

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Aaron D. Kofman ◽  
Emma K. Sizemore ◽  
Joshua F. Detelich ◽  
Benjamin Albrecht ◽  
Anne L. Piantadosi
Keyword(s):  
Cardiac Dysfunction ◽  
Clinical Characteristics ◽  
Kidney Injury ◽  
Clinical Findings ◽  
Low Grade ◽  
Rare Form ◽  
Case Presentation ◽  
Lymph Node Swelling ◽  
Inflammatory Syndrome

Abstract Background A healthy 25-year-old woman developed COVID-19 disease with clinical characteristics resembling Multisystem Inflammatory Syndrome in Children (MIS-C), a rare form of COVID-19 described primarily in children under 21 years of age. Case presentation The patient presented with 1 week of weakness, dyspnea, and low-grade fevers, followed by mild cough, sore throat, vomiting, diarrhea, and lymph node swelling. She was otherwise healthy, with no prior medical history. Her hospital course was notable for profound acute kidney injury, leukocytosis, hypotension, and cardiac dysfunction requiring ICU admission and vasopressor support. MIS-C-like illness secondary to COVID-19 was suspected due to physical exam findings of conjunctivitis, mucositis, and shock. She improved following IVIG, aspirin, and supportive care, and was discharged on hospital day 5. Conclusion MIS-C-like illness should be considered in adults presenting with atypical clinical findings and concern for COVID-19. Further research is needed to support the role of IVIG and aspirin in this patient population.

scholarly journals Clinical Characteristics of Asymptomatic and Symptomatic Pediatric Coronavirus Disease 2019 (COVID-19): A Systematic Review

Medicina ◽  
2020 ◽  
Vol 56 (9) ◽  
pp. 474
Author(s):  
Sojung Yoon ◽  
Han Li ◽  
Keum Hwa Lee ◽  
Sung Hwi Hong ◽  
Dohoon Kim ◽  
...  
Keyword(s):  
Clinical Characteristics ◽  
Clinical Laboratory ◽  
Case Reports ◽  
Meta Analysis ◽  
Clinical Findings ◽  
Chest Ct ◽  
Therapeutic Interventions ◽  
Symptomatic Infection ◽  
Abnormal Chest ◽  
Study Designs

Background and objectives: Characterization of pediatric coronavirus disease 2019 (COVID-19) is necessary to control the pandemic, as asymptomatic or mildly infected children may act as carriers. To date, there are limited reports describing differences in clinical, laboratory, and radiological characteristics between asymptomatic and symptomatic infection, and between younger and older pediatric patients. The objective of this study is to compare characteristics among: (1) asymptomatic versus symptomatic and (2) less than 10 versus greater or equal to 10 years old pediatric COVID-19 patients. Materials and Methods: We searched for all terms related to pediatric COVID-19 in electronic databases (Embase, Medline, PubMed, and Web of Science) for articles from January 2020. This protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. Results: Eligible study designs included case reports and series, while we excluded comments/letters, reviews, and literature not written in English. Initially, 817 articles were identified. Forty-three articles encompassing 158 confirmed pediatric COVID-19 cases were included in the final analyses. Lymphocytosis and high CRP were associated with symptomatic infection. Abnormal chest CT more accurately detected asymptomatic COVID-19 in older patients than in younger ones, but clinical characteristics were similar between older and younger patients. Conclusions: Chest CT scan findings are untrustworthy in younger children with COVID-19 as compared with clinical findings, or significant differences in findings between asymptomatic to symptomatic children. Further studies evaluating pediatric COVID-19 could contribute to potential therapeutic interventions and preventive strategies to limit spreading.

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