scholarly journals Neonatal screening and genotype-phenotype correlation of hyperphenylalaninemia in the Chinese population

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Xin Wang ◽  
Yanyun Wang ◽  
Dingyuan Ma ◽  
Zhilei Zhang ◽  
Yahong Li ◽  
...  
Keyword(s):  
Neonatal Screening ◽  
Phenylalanine Hydroxylase ◽  
Laboratory Data ◽  
Molecular Characteristics ◽  
Phenotype Correlation ◽  
Common Amino Acid ◽  
Appropriate Treatment ◽  
Clinical Presentations ◽  
Average Current

Abstract Background Hyperphenylalaninemia (HPA) is the most common amino acid metabolic disease involving phenylalanine hydroxylase (PAH, OMIM*612,349) deficiency or coenzyme tetrahydrobiopterin (BH4) deficiency. Patients with severe HPA often have a difficult life. Early diagnosis of HPA before the development of symptoms is possible via neonatal screening, facilitating appropriate treatment and reducing mortality and disability rates. This study revealed the prevalence, mutational and phenotypic spectrum, and prognosis of HPA by neonatal screening from January 2001 to September 2020 in Nanjing, Jiangsu Province, China. Methods Through a retrospective analysis of the information available in the neonatal screening database, the clinical presentations, laboratory data, molecular characteristics and treatment follow-up data of HPA patients detected by neonatal screening were evaluated. Results We diagnosed 181 patients with HPA from 1 to 957 newborns, giving an incidence of 1:6873. Among these patients, 177 were identified as PAH deficient and four patients were BH4 deficient. The average current age of the patients was 6.38 years old. The most common mutations of PAH were c.728 C > A/ p.Arg243Gln (13.83 %), c.158G > A/ p.Arg53His (9.57 %), c.611 A > G/ p.Tyr204Cys (7.44 %), and c.721 C > T/ p.Arg241Cys (6.38 %). Conclusions This study revealed the prevalence, phenotype-genotype, and prognosis of HPA in China and contributes to the updating of PAHD data for China and worldwide. Our study not only expanded the spectrum of phenotypes and genotype but also provided a valuable tool for improved genetic counseling and management of future cases.

scholarly journals Neonatal Screening and Genotype-Phenotype Correlation of 21-Hydroxylase Deficiency in the Chinese Population

2021 ◽  
Vol 11 ◽  
Author(s):  
Xin Wang ◽  
Yanyun Wang ◽  
Dingyuan Ma ◽  
Zhilei Zhang ◽  
Yahong Li ◽  
...  
Keyword(s):  
Neonatal Screening ◽  
Chinese Population ◽  
Eastern China ◽  
Laboratory Data ◽  
Adrenal Crisis ◽  
Molecular Characteristics ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Genotype Phenotype Correlation ◽  
21 Hydroxylase Deficiency

Background: Congenital adrenal hyperplasia (CAH) is a group of autosomal recessive disorders encompassing enzyme deficiencies in the adrenal steroidogenesis pathway that leads to impaired cortisol biosynthesis. 21-hydroxylase deficiency (21-OHD) is the most common type of CAH. Severe cases of 21-OHD may result in death during the neonatal or infancy periods or sterility in later life. The early detection and timely treatment of 21-OHD are essential. This study aimed to summarize the clinical and genotype characteristics of 21-OHD patients detected by neonatal screening in Nanjing, Jiangsu province of China from 2000 to 2019.Methods: Through a retrospective analysis of medical records, the clinical presentations, laboratory data, and molecular characteristics of 21-OHD patients detected by neonatal screening were evaluated.Results: Of the 1,211,322 newborns who were screened, 62 cases were diagnosed with 21-OHD with an incidence of 1:19858. 58 patients were identified with the classical salt-wasting type (SW) 21-OHD and four patients were identified with simple virilizing type (SV) 21-OHD. Amongst these patients, 19 cases patients accepted genetic analysis, and another 40 cases were received from other cities in Eastern China. Eighteen different variants were found in the CYP21A2 gene. The most frequent variants was c.293-13A/C>G (36.29%). The most severe clinical manifestations were caused by large deletions or conversions of CYP21A2.Conclusions: This study suggested that neonatal screening effectively leads to the early diagnosis of 21-OHD and reduces fatal adrenal crisis. Our data provide additional information on the occurrence and genotype-phenotype correlation of 21-OHD in the Chinese population which can be used to better inform treatment and improve prognosis.

scholarly journals Autoimmune encephalitis in a South Asian population

BMC Neurology ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Nilanka Wickramasinghe ◽  
Dhanushka Dasanayake ◽  
Neelika Malavige ◽  
Rajiva de Silva ◽  
Thashi Chang
Keyword(s):  
Sri Lanka ◽  
Psychiatric Symptoms ◽  
South Asians ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Autoimmune Encephalitis ◽  
Asian Population ◽  
South Asian Population ◽  
Clinical Presentations

Abstract Background Autoimmune encephalitis (AE) is now considered a main, potentially curable cause of encephalitis, but remains conspicuously underreported from South Asia. We studied the clinical characteristics in relation to their antibody status and outcomes of patients presenting with AE in Sri Lanka. Methods Patients admitting to government hospitals who were clinically suspected of AE by an on-site neurologist were prospectively recruited over a period of 12 months. Sera and cerebrospinal fluid were tested for NMDAR, AMPAR1, AMPAR2, LGI1, CASPR2, GABARB1/B2 antibodies (Ab) using commercial cell-based assays. Demographic, clinical and laboratory data were compiled into an investigator-administered proforma. Patients were reviewed at 1 year follow up either in person or via telephone. Results One-hundred and forty-two patients from 21 of 25 districts in Sri Lanka (median age = 20.5 years; range 1–86 years; females = 61.3%) were recruited. Of them, 65 (45.8%; median age = 19 years; range 1–86 years; females = 64.6%) fulfilled diagnostic criteria for probable NMDAR-antibody encephalitis (NMDARE) and 6 (4.2%; median age = 44 years; range 28–71 years; females = 83.3%) limbic encephalitis (LE). Abnormal behaviour (95.3%), seizures (81.5%) and movement disorders (69.2%) were the most frequent clinical manifestations of probable NMDARE. NMDAR-antibodies were detectable in 29 (44.6%) and not detectable in 36 in CSF of probable-NMDARE patients. Abnormal EEG was more frequent (p = 0.003) while a worse outcome (OR = 2.78; 95% CI = 0.88–9.09) and deaths (OR = 2.38; 95% CI = 0.67–8.33) were more likely in antibody-negative than antibody-positive probable-NMDARE. Most patients with LE had amnesia (50%) and/or confusion (100%) with agitation (83.3%) and seizures (100%) but none had detectable antibodies to any of the antigens tested. Conclusions NMDARE is the commonest type of AE among South Asians as is the case worldwide. Clinical presentations of NMDARAb-positive and NMDARAb-negative AE patients do not significantly differ but EEG may be a useful marker of an autoimmune basis for psychiatric symptoms.

scholarly journals Hereditary thrombocytopenias: a growing list of disorders

Hematology ◽  
2017 ◽  
Vol 2017 (1) ◽  
pp. 385-399 ◽  
Author(s):  
Patrizia Noris ◽  
Alessandro Pecci
Keyword(s):  
High Throughput Sequencing ◽  
Hematological Malignancies ◽  
Bone Marrow Failure ◽  
Clinical Problem ◽  
Molecular Defects ◽  
Appropriate Treatment ◽  
Clinical Presentations ◽  
Current Scenario ◽  
Major Clinical Problem

Abstract The introduction of high throughput sequencing (HTS) techniques greatly improved the knowledge of inherited thrombocytopenias (ITs) over the last few years. A total of 33 different forms caused by molecular defects affecting at least 32 genes have been identified; along with the discovery of new disease-causing genes, pathogenetic mechanisms of thrombocytopenia have been better elucidated. Although the clinical picture of ITs is heterogeneous, bleeding has been long considered the major clinical problem for patients with IT. Conversely, the current scenario indicates that patients with some of the most common ITs are at risk of developing additional disorders more dangerous than thrombocytopenia itself during life. In particular, MYH9 mutations result in congenital macrothrombocytopenia and predispose to kidney failure, hearing loss, and cataracts, MPL and MECOM mutations cause congenital thrombocytopenia evolving into bone marrow failure, whereas thrombocytopenias caused by RUNX1, ANKRD26, and ETV6 mutations are characterized by predisposition to hematological malignancies. Making a definite diagnosis of these forms is crucial to provide patients with the most appropriate treatment, follow-up, and counseling. In this review, the ITs known to date are discussed, with specific attention focused on clinical presentations and diagnostic criteria for ITs predisposing to additional illnesses. The currently available therapeutic options for the different forms of IT are illustrated.

Progressive Leukodystrophy-Like Demyelinating Syndromes with MOG-Antibodies in Children: A Rare Under-Recognized Phenotype

2021 ◽  
Author(s):  
Elise Yazbeck ◽  
Hélène Maurey ◽  
Carole Leroy ◽  
Philippe Horellou ◽  
Silvia Napuri ◽  
...  
Keyword(s):  
Brain Magnetic Resonance Imaging ◽  
Brain Biopsy ◽  
Active Immunotherapy ◽  
Oligoclonal Bands ◽  
Second Child ◽  
Fluid Analysis ◽  
Appropriate Treatment ◽  
Neurological Prognosis ◽  
Mog Antibodies

AbstractAcquired demyelinating syndromes (ADS) are frequently associated with myelin oligodendrocytes glycoprotein (MOG) antibodies in children. Clinical phenotypes are heterogeneous and may delay the diagnosis, especially when they relapse and are atypical, mimicking diseases such as multiple sclerosis or neuromyelitis optica spectrum disorders . Here, we describe two children: one with a progressive cognitive and behavioral deterioration with seizures after only one relapse and the other with similar clinical impairments associated with multiple relapses. Brain magnetic resonance imaging revealed a subsequent progressive leukodystrophy-like lesion with diffuse bilateral white matter injuries in both patients. Cerebrospinal fluid analysis showed pleiocytosis, increased level of proteins with no oligoclonal bands. Metabolic and inflammatory blood markers were all negative. Brain biopsy was performed in the second child and nonspecific inflammatory lesions with no argument for histiocytosis or tumor were observed. Clinical and radiological stabilization were obtained after active immunotherapy. Retrospective analysis of anti-MOG antibodies in these two children was positive at the earlier stage of the disease and turned negative after treatment and during follow-up. Leukodystrophy-like ADS with anti-MOG-antibodies may display distinct progressive phenotype and have a severe neurological prognosis. Early diagnosis and appropriate treatment may improve outcome in these children.

scholarly journals Clinical presentations and long term prognosis of childhood onset polyarteritis nodosa in single centre of Korea

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeong-Seon Lee ◽  
Joong-Gon Kim ◽  
Soyoung Lee
Keyword(s):  
Polyarteritis Nodosa ◽  
Clinical Manifestations ◽  
Long Term Outcomes ◽  
Childhood Onset ◽  
Laboratory Findings ◽  
Clinical Presentations ◽  
Long Term Prognosis ◽  
Digital Amputation

AbstractChildhood-onset polyarteritis nodosa (PAN) is a rare and systemic necrotising vasculitis in children affecting small- to medium-sized arteries. To date, there have been only a few reports because of its rarity. Thus, we aimed to investigate the clinical manifestations, laboratory findings, treatment, and long-term outcomes in patients with childhood-onset PAN and to evaluate the usefulness of the paediatric vasculitis activity score (PVAS). We retrospectively analysed the data of nine patients with childhood-onset PAN from March 2003 to February 2020. The median ages at symptom onset, diagnosis, and follow-up duration were 7.6 (3–17.5), 7.7 (3.5–17.6), and 7.0 (1.6–16.3) years, respectively. All patients had constitutional symptoms and skin manifestations, while five exhibited Raynaud’s phenomenon. Organ involvement was observed in one patient. The median PVAS at diagnosis was 7 (range: 2–32). Prednisolone was initially used for induction in all patients, and other drugs were added in cases refractory to prednisolone. All patients survived, but three patients with high PVAS at diagnosis experienced irreversible sequelae, including intracranial haemorrhage and digital amputation. In conclusion, early diagnosis and treatment may minimise sequelae in patients with childhood-onset PAN. This study suggests that high PVAS score at diagnosis may be associated with poor prognosis.

scholarly journals Squamous cell carcinoma of the scrotum in HIV: two case reports

2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Jeff John ◽  
Ken Kesner ◽  
John Lazarus
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Case Reports ◽  
Treatment Options ◽  
Punch Biopsy ◽  
Delayed Treatment ◽  
Clinical Presentations ◽  
T1 N0 M0

Abstract Background Squamous cell carcinoma (SCC) of the scrotum was the first malignancy known to be associated with exposure to an occupational carcinogen—in this case, soot trapped in the breeches of chimney sweeps. Better civil rules and regulations and the replacement of hearths with other forms of heating have rendered SCC of the scrotum a rarity. We report two cases of scrotal SCC with vastly differing clinical presentations and management. Case presentation Case 1 had T1 N0 M0 disease and presented with a small (< 2 cm), innocuous-looking, non-healing ulcer of eight years duration. A punch biopsy revealed a superficially invasive SCC confirmed on immunohistochemical profiling. A wide local excision of the lesion was subsequently performed. Follow-up at three years showed no signs of recurrence. Case 2 presented with T4 N1 M1 disease and rapidly progressing locally destructive mass. A punch biopsy of the scrotal lesion confirmed invasive moderately differentiated focally keratinising SCC. The metastatic evaluation confirmed the presence of metastatic, extensive para-aortic lymphadenopathy. He was managed with cisplatin-based chemoradiotherapy. Conclusion Early detection and management of patients with SCC of the scrotum are essential. If the diagnosis is delayed, treatment options become limited, and the prognosis is poor. Notwithstanding the rarity of this disease, multicentre trials are needed to provide more precise guidelines as to the optimal management of these patients.

scholarly journals AB0533 ANTI-NEUTROPHIL CYTOPLASMIC ANTIBODY (ANCA) IN GENERAL POPULATION WITHOUT ANCA ASSOCIATED VASCULITIS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1563.3-1563
Author(s):  
H. Tamaki ◽  
S. Fukui ◽  
T. Nakai ◽  
G. Kidoguchi ◽  
S. Kawaai ◽  
...  
Keyword(s):  
Risk Factors ◽  
Autoimmune Disease ◽  
General Population ◽  
Granulomatosis With Polyangiitis ◽  
Dietary Habits ◽  
Laboratory Data ◽  
Clinical Manifestations ◽  
Anca Associated Vasculitis ◽  
The Mean

Background:Currently it is hypothesized that many systemic autoimmune diseases occur due to environmental risk factors in addition to genetic risk factors. Anti-Neutrophil Cytoplasmic Antibody (ANCA) is mainly associated with three systemic autoimmune disease including granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA). It is known that ANCA can be positive before clinical symptoms in patients with known diagnosis of GPA and ANCA titers rise before clinical manifestations appear. However, prevalence of ANCA among general population is not well known. It has not been described as well how many of people with positive ANCA eventually develop clinical manifestations of ANCA associated Vasculitis.Objectives:This study aims to estimate prevalence of ANCA in general population without ANCA associated Vasculitis. It also describes natural disease course of people with positive ANCA without ANCA associated Vasculitis. Risk factors for positive ANCA are also analyzed.Methods:This is a single center retrospective study at Center for Preventive Medicine of St. Luke’s International Hospital in Tokyo. ANCA was checked among the patients who wished to between 2018 and 2019. St. Luke’s Health Check-up Database (SLHCD) was utilized to collect the data. The patients whose serum was measured for ANCA were identified. The data for basic demographics, social habits, dietary habits and laboratory data were extracted. The charts of the patients with positive ANCA were reviewed.Results:Sera of total 1204 people were checked for ANCA. Of these 1204 people, 587 (48.8%) are male and the mean age was 55.8 years (32.6 to 79). There were total 11 patients with positive ANCA. Myeloperoxidase ANCA (MPO-ANCA) was positive for 3 patients and proteinase 3 ANCA (PR3-ANCA) was positive for 8 patients. Of these 11 patients, 5 were male (45.5%) and the mean age was 54.6 years. Two patients had history of autoimmune disease (primary biliary cirrhosis and ulcerative colitis). Five patients were evaluated by rheumatologists with the median follow-up period of 274 days. None of them developed clinical signs and symptoms of ANCA associated Vasculitis. Four out of five patients had ANCA checked later, two of which turned negative. The prevalence of ANCA in this cohort was 0.9% (95% confidence interval [95% CI]: 0.5% to 1.6%). Univariate analysis was performed to identify risk factors of positive ANCA. The variables analyzed include age, gender, body mass index (BMI), smoking habits, alcohol intake, dietary habits (fruits, fish, red meat), hypertension, dyslipidemia, and laboratory data. None of these variables demonstrated statistically significant differences except for positive rheumatoid factor (ANCA positive group: 33 % vs ANCA negative group: 9.1%, p value = 0.044).Conclusion:The prevalence of ANCA in this cohort was 0.9% (95% CI: 0.5% to 1.6%). None of them who had a follow-up developed ANCA associated Vasculitis during the follow-up period. Longer follow-up and more patients are necessary to determine natural course of people with positive ANCA.Disclosure of Interests:None declared

scholarly journals Role of Radiotherapy in Recurrent Intra-Abdominal Yolk Sac Tumor

2021 ◽  
pp. 1010-1018
Author(s):  
Marhendra Satria Utama ◽  
Andi Kurniadi ◽  
A.A. Citra Yunda Prahastiwi ◽  
Antony A. Adibrata
Keyword(s):  
Case Reports ◽  
Yolk Sac ◽  
Yolk Sac Tumor ◽  
Appropriate Treatment ◽  
Curative Radiotherapy ◽  
Chief Complaints ◽  
Abdominal Mri ◽  
Malignant Germ Cell Tumor

Yolk sac tumor (YST) is a rare malignant germ cell tumor with no appropriate treatment strategy to date. However, patients are treated on a case-to-case basis as per various case reports that have been published. Here, we present a case of 27-year-old female patient who presented to us with chief complaints of severe abdominal pain associated with leucorrhea. She previously had a similar pain episode, which was then evaluated by a multidisciplinary team. She was diagnosed with YST. After that, she underwent 6 cycles of chemotherapy, but there was no improvement. Then the medical oncologist referred her to performed radiotherapy. Then, the radiation oncologist decided to give her curative radiotherapy of 3D-CRT. After completing her sessions, she felt better and clinically improving. After that, she was discharged and scheduled a follow-up visit for first evaluation. At her follow-up visit, she was feeling well, and we decided to have an abdominal MRI.

scholarly journals Current Perspectives on Neonatal Screening for Propionic Acidemia in Japan: An Unexpectedly High Incidence of Patients with Mild Disease Caused by a Common PCCB Variant

2021 ◽  
Vol 7 (3) ◽  
pp. 35
Author(s):  
Go Tajima ◽  
Reiko Kagawa ◽  
Fumiaki Sakura ◽  
Akari Nakamura-Utsunomiya ◽  
Keiichi Hara ◽  
...  
Keyword(s):  
Neonatal Screening ◽  
Acid Metabolism ◽  
Neonatal Period ◽  
Propionic Acidemia ◽  
Cardiac Complications ◽  
Mild Disease ◽  
Follow Up Study ◽  
Organic Acid Metabolism ◽  
High Incidence

Propionic acidemia (PA) is a disorder of organic acid metabolism which typically presents with acute encephalopathy-like symptoms associated with metabolic acidosis and hyperammonemia during the neonatal period. The estimated incidence of symptomatic PA in Japan is 1/400,000. The introduction of neonatal screening using tandem mass spectrometry has revealed a far higher disease frequency of approximately 1/45,000 live births due to a prevalent variant of c.1304T>C (p.Y435C) in PCCB, which codes β-subunit of propionyl-CoA carboxylase. Our questionnaire-based follow-up study reveals that most of these patients remain asymptomatic. However, reports on symptomatic patients exhibiting cardiac complications such as cardiomyopathy and QT prolongation have been increasing. Moreover, there were even cases in which these cardiac complications were the only symptoms related to PA. A currently ongoing study is investigating the risk of cardiac complications in patients with neonatal screening-detected PA caused by this common variant.

Acupuncture in Patients with Valvular Heart Disease and Prosthetic Valves

2003 ◽  
Vol 21 (3) ◽  
pp. 87-91 ◽  
Author(s):  
Anthony Stellon
Keyword(s):  
Heart Disease ◽  
Valvular Heart Disease ◽  
Acupuncture Treatment ◽  
Laboratory Data ◽  
Median Number ◽  
Prophylactic Antibiotics ◽  
Blood Cultures ◽  
Prosthetic Valves ◽  
Small Cohort

Endocarditis has been reported in patients with valvular heart disease who have undergone acupuncture treatment, although most have been associated with the use of semi-permanent needles. This has led reviewers to suggest that acupuncture may not only be contraindicated in such patients but that prophylactic antibiotics should be given. This study investigated the use of acupuncture treatment in patients with proven valvular heart disease and observed whether endocarditis developed in such patients. All patients in a single-handed GP practice with proven valvular heart disease, including those with prosthetic valves, were identified over a ten-year period. Those who had undergone acupuncture treatment underwent a clinical examination and diagnostic tests, which focused on the signs, symptoms and laboratory criteria for the diagnosis of endocarditis and included a transthoracic echocardiogram. Autopsy findings were reviewed in any patient who died. Based on these clinical and laboratory data, using the modified Duke's criteria for the diagnosis of endocarditis, patients were identified as having definite or possible endocarditis, or the diagnosis was rejected. All patients underwent brief acupuncture with no skin disinfectant and no prophylactic antibiotics were given. Semi-permanent needles were avoided. Thirty-six patients with valvular heart disease underwent a total of 479 acupuncture treatments over a ten-year period. The median number of treatments was 9 (range 1 – 72), with a follow-up after treatment of 5.75 years (range 0.5 – 10 years). Definite endocarditis was not found in any patient, but two patients had possible endocarditis, eventually discounted by both negative blood cultures and echocardiography. In conclusion, brief acupuncture was safe in this small cohort of valvular heart disease patients and no case of endocarditis was detected over a ten-year period.

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