scholarly journals Hypophosphatasia in children. Three faces of one disease

2020 ◽  
Vol 3 (2) ◽  
pp. 136-141
Author(s):  
S.A. Boykov ◽  
◽  
I.Yu. Chernyak ◽  
N.S. Shatokhina ◽  
E.Yu. Gurkina ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Clinical Symptoms ◽  
Bone Mineralization ◽  
Case Reports ◽  
Molecular Genetic ◽  
Case Series ◽  
Alp Activity ◽  
Systemic Manifestations ◽  
Molecular Genetic Test ◽  
Reduced Mobility

Hypophosphatasia (HPP) is a rare multisystem inherited metabolic disorder caused by mutations in ALPL gene that encodes tissue nonspecific alkaline phosphatase responsible for bone mineralization. HPP is characterized by impaired bone mineralization, skeletal abnormalities, and systemic manifestations which result in significant morbidity and mortality. Clinical presentations of HPP vary greatly. Early (perinatal and infantile) HPP is characterized by the most severe symptoms, i.e., respiratory and neurological disorders are of crucial importance being the leading causes of death. Progressive skeletal impairment, rickets-like deformities, reduced mobility, and severe disability are typical of childhood-onset HPP. The biochemical hallmark of HPP is low alkaline phosphatase (ALP) activity. HPP diagnosis is verified by clinical symptoms in combination with persistently low ALP activity (adjusted for age and sex). Molecular genetic test to identify ALPL gene mutation is performed as needed. Three case reports addresses authors’ experience with the diagnosis and treatment for HPP.Keywords: hypophosphatasia, case series, alkaline phosphatase, impaired bone mineralization, asfotase alfa.For citation: Boykov S.A., Chernyak I.Yu., Shatokhina N.S. et al. Hypophosphatasia in children. Three faces of one disease. Russian Journal of Woman and Child Health. 2020;3(2):136–141. DOI: 10.32364/2618-8430-2020-3-2-136-141.

scholarly journals MON-196 A Single-Center Experience of Patients with Metastatic Pheochromocytoma/Paraganglioma Treated with 177Lu-DOTATATE

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Anna Roslyakova ◽  
Dmitry Beltsevich ◽  
Michail Plotkin ◽  
Pavel Rumyantsev ◽  
Daria Ladygina
Keyword(s):  
Overall Survival ◽  
Survival Rate ◽  
Chromogranin A ◽  
Clinical Symptoms ◽  
Case Reports ◽  
Clinical Care ◽  
Case Series ◽  
Peptide Receptor Radionuclide Therapy ◽  
Optimal Strategies ◽  
Metastatic Progression

Abstract The prevalence of metastatic pheochromocytoma/paraganglioma (PPGL) is reported to be 3% to 36% of all the cases. The five-year overall survival rate of such patients ranges from 40 to 77%. The management of metastatic PPGL is challenging taking into account the fact that the optimal strategies for clinical care beyond surgical resection are not guided yet. Peptide receptor radionuclide therapy (PRRT) using somatostatin analogues is effective in other neuroendocrine tumours, can be indicated in patients with positive scans for the respective radiopharmaceuticals. We report preliminary data of the prospective study aimed to assess the safety and efficacy outcomes of 177Lu-DOTATATE for 6 patients with histologically confirmed PPGLs with metastatic progression after the complete PPGL surgery. The mean age of our cohort was 53 years (range 14–73); an equal number of male and female patients was included. Two of them had germline mutations in RET and SDHB genes, respectively. Radiological response utilized RECIST 1.1 criteria; toxicity was graded according to common terminology criteria for adverse events version 4. PPRT scheme varied between three and four cycles. Partial response (PR) was achieved in one and stable disease (SD) in four 4 patients. One patient had treatment refractory with disease progression and dramatic increase of chromogranin A concentration (+268%). Biochemical response (>50% decrease) of chromogranin A was found in 1/6 patients and of catecholamines in 2/6 patients. No hematological or kidney toxicity grade 3–4 was registered. Median overall survival and median progression-free survival rate will be reported after the end of the study. To date, about 250 PPGL patients have been treated with PRRT. PRRT using 177Lu-DOTA-SSAs has shown promise for treatment of PPGLs with improvement of clinical symptoms and/or disease control in the setting of retrospective small case reports or case series. However, more well-designed prospective studies are required to confirm these findings.

scholarly journals Prevalence of low alkaline phosphatase activity in laboratory assessment: Is hypophosphatasia an underdiagnosed disease?

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Tobias Schmidt ◽  
Constantin Schmidt ◽  
Michael Amling ◽  
Jan Kramer ◽  
Florian Barvencik
Keyword(s):  
Alkaline Phosphatase ◽  
Bone Mineralization ◽  
Population Based ◽  
Laboratory Measurements ◽  
Northern Germany ◽  
Laboratory Assessment ◽  
Alp Activity ◽  
A Value ◽  
Single Laboratory ◽  
Dental Mineralization

Abstract Background Tissue-nonspecific alkaline phosphatase (TNSALP) encoded by the ALPL gene is of particular importance for bone mineralization. Mutation in the ALPL gene can lead to persistent low ALP activity resulting in the rare disease Hypophosphatasia (HPP) that is characterized by disturbed bone and dental mineralization. While severe forms are extremely rare with an estimated prevalence of 1/100.000, recent studies suggest that moderate form caused by heterozygous mutations are much more frequent with an estimated prevalence of 1/508. The purpose of this study was to estimate the prevalence of low AP levels in the population based on laboratory measurements. Methods In this study, the prevalence of low AP activity and elevated pyridoxal-5-phosphate (PLP) levels was analyzed in 6.918.126 measurements from 2011 to 2016 at a single laboratory in northern Germany. Only laboratory values of subjects older than 18 years of age were included. Only the first measurement was included, all repeated values were excluded. Results In total, 8.46% of the measurements of a total of 6.918.126 values showed a value < 30 U/L. 0.59% of the subjects with an ALP activity below 30 U/L had an additional PLP measurement. Here, 6.09% showed elevated pyridoxal-5-phosphate (PLP) levels. This suggest that 0.52% (1:194) of subjects show laboratory signs of HPP. Conclusion These data support the genetic estimation that the prevalence of moderate forms of HPP may be significantly higher than expected. Based on these data, we recommend automatically measurement of PLP in the case of low ALP activity and a notification to the ordering physician that HPP should be included in the differential diagnosis and further exploration is recommended.

scholarly journals Spontaneous retroclival hematoma in pituitary apoplexy: case series

2015 ◽  
Vol 123 (3) ◽  
pp. 808-812 ◽  
Author(s):  
Avetis Azizyan ◽  
Joseph M. Miller ◽  
Ramzi I. Azzam ◽  
Marcel M. Maya ◽  
Pouyan Famini ◽  
...  
Keyword(s):  
Pituitary Apoplexy ◽  
Clinical Symptoms ◽  
Case Reports ◽  
Brain Mri ◽  
Cranial Nerves ◽  
Case Series ◽  
Visual Disturbance ◽  
Sudden Onset ◽  
Laboratory Findings ◽  
Presenting Symptoms

OBJECT Pituitary apoplexy is a rare and potentially life-threatening disorder that is most commonly characterized by a combination of sudden headache, visual disturbance, and hypothalamic/hormonal dysfunction. In many cases, there is hemorrhagic infarction of an underlying pituitary adenoma. The resulting clinical symptoms are due to compression of the remaining pituitary, cavernous sinuses, or cranial nerves. However, there are only 2 case reports in the literature describing spontaneous retroclival expansion of hemorrhage secondary to pituitary apoplexy. Ten cases of this entity with a review of the literature are presented here. METHODS This is a single-institution retrospective review of 2598 patients with sellar and parasellar masses during the 10-year period between 1999 and 2009. The pituitary and brain MRI and MRI studies were reviewed by 2 neuroradiologists for evidence of apoplexy, with particular attention given to retroclival extension. RESULTS Eighteen patients (13 men and 5 women; mean age 54 years) were identified with presenting symptoms of sudden onset of headache and ophthalmoplegia, and laboratory findings consistent with pituitary apoplexy. Ten of these patients (8 men and 2 women; mean age 55 years) had imaging findings consistent with retroclival hematoma. CONCLUSIONS Retroclival hemorrhage was seen in the majority of cases of pituitary apoplexy (56%), suggesting that it is more common than previously thought.

scholarly journals Neurological and Neurosurgical Aspects of Hypophosphatasia

2018 ◽  
Vol 15 (3) ◽  
pp. 249-254
Author(s):  
Vadim P. Ivanov ◽  
Leonid A. Satanin ◽  
Alexander V. Kim ◽  
Ludmila M. Kuzenkova ◽  
Tea V. Margieva ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Attention Deficit Disorder ◽  
Alkaline Phosphatase Level ◽  
Bone Mineralization ◽  
Clinical Manifestations ◽  
Psychomotor Development ◽  
Systemic Manifestations ◽  
Severity Of The Disease ◽  
Tract Damage ◽  
Low Activity

Hypophosphatasia is a rare hereditary progressive disease caused by a mutation in ALPL gene and characterized by low activity of alkaline phosphatase. Due to the disruption of the bone mineralization process, ricket-like deformations of the skeleton occur in the clinic picture more frequently but other systemic manifestations can be also observed as respiratory insufficiency, urinary tract damage, and neurological disorders. Seizures, delayed physical and psychomotor development, attention deficit disorder, muscle weakness, fatigue, intracranial hypertension associated with the development of craniosynostosis are revealed in these patients. The severity of the disease depends on age: the highest mortality is reported in younger patients, in perinatal and infantile forms of hypophosphatasia. Diagnosis is based on the identification of specific clinical manifestations: retardation of growth and development, skeletal deformities, pain in muscles and joints, premature tooth loss. In laboratory tests, a steady decrease in alkaline phosphatase level is detected taking into account age and sex specification. If possible, alkaline phosphatase substrates are measured: levels of pyridoxal-5-phosphate in the blood and phosphoethanolamine in urine are higher at low enzyme activity. Radiographs of long bones typically reveal characteristic ‘tongues’ of lucency projecting from growth plates into metaphyses, hypomineralization, osteopenia, various kinds of deformation. All patients with suspected hypophosphatasia should be consulted by a clinical geneticist and evaluated to identify possible mutation in the ALPL gene.

scholarly journals Surgical Treatment for Profunda Femoris Artery Aneurysms: Five Case Reports

2015 ◽  
Vol 2015 ◽  
pp. 1-5 ◽  
Author(s):  
Kimihiro Igari ◽  
Toshifumi Kudo ◽  
Takahiro Toyofuku ◽  
Yoshinori Inoue
Keyword(s):  
Blood Flow ◽  
Clinical Symptoms ◽  
Case Reports ◽  
Case Series ◽  
Artery Aneurysm ◽  
Vascular Reconstruction ◽  
Rare Entity ◽  
Graft Replacement ◽  
Profunda Femoris Artery ◽  
Profunda Femoris

Profunda femoris artery aneurysm (PFAA) is an extremely rare entity, with most cases being asymptomatic, which makes obtaining an early diagnosis difficult. We herein report a case series of PFAA, in which more than half of the PFAAs, which presented with no clinical symptoms, were discovered incidentally. All PFAAs were treated surgically with aneurysmectomy with or without vascular reconstruction. In cases involving a patent superficial femoral artery (SFA), graft replacement of the profunda femoris artery (PFA) is not mandatory; however, preserving the blood flow of the PFA is necessary to maintain lower extremity perfusion in patients with occlusion of the SFA. Therefore, the treatment of PFAAs should include appropriate management of both the aneurysmectomy and graft replacement, if possible.

scholarly journals Case Report: Efficacy of Reduced Doses of Asfotase Alfa Replacement Therapy in an Infant With Hypophosphatasia Who Lacked Severe Clinical Symptoms

2020 ◽  
Vol 11 ◽  
Author(s):  
Yasuko Fujisawa ◽  
Taichi Kitaoka ◽  
Hiroyuki Ono ◽  
Shinichi Nakashima ◽  
Keiichi Ozono ◽  
...  
Keyword(s):  
Alkaline Phosphatase ◽  
Enzyme Replacement Therapy ◽  
Replacement Therapy ◽  
Serum Calcium ◽  
Reference Range ◽  
Clinical Symptoms ◽  
Bone Mineralization ◽  
Clinical Severity ◽  
Enzyme Replacement ◽  
Asfotase Alfa

BackgroundHypophosphatasia is a rare bone disease characterized by impaired bone mineralization and low alkaline phosphatase activity. Here, we describe the course of bone-targeted enzyme replacement therapy with asfotase alpha for a female infant patient with hypophosphatasia who lacked apparent severe clinical symptoms.Case presentationThe patient exhibited low serum alkaline phosphatase (60 U/L; age-matched reference range, 520–1,580) in a routine laboratory test at birth. Further examinations revealed skeletal demineralization and rachitic changes, as well as elevated levels of serum calcium (2.80 mmol/L; reference range, 2.25–2.75 mmol/L) and ionic phosphate (3.17 mmol/L; reference range, 1.62–2.48 mmol/L), which are typical features in patients with hypophosphatasia. Sequencing analysis of the tissue-nonspecific alkaline phosphatase (TNSALP) gene identified two pathogenic mutations: c.406C&gt;T, p.Arg136Cys and c.979T&gt;C, p.Phe327Leu. Thus, the patient was diagnosed with hypophosphatasia. At the age of 37 days, she began enzyme replacement therapy using asfotase alpha at the standard dose of 6 mg/kg/week. Initial therapy from the age of 37 days to the age of 58 days substantially improved rickets signs in the patient; it also provided immediate normalization of serum calcium and ionic phosphate levels. However, serum ionic phosphate returned to a high level (2.72 mmol/L), which was presumed to be a side effect of asfotase alpha. Thus, the patient’s asfotase alfa treatment was reduced to 2 mg/kg/week, which allowed her to maintain normal or near normal skeletal features thereafter, along with lowered serum ionic phosphate levels. Because the patient exhibited slight distal metaphyseal demineralization in the knee at the age of 2 years and 6 months, her asfotase alfa treatment was increased to 2.4 mg/kg/week. No signs of deterioration in bone mineralization were observed thereafter. At the age of 3 years, the patient’s motor and psychological development both appeared normal, compared with children of similar age.ConclusionThis is the first report in which reduced doses of asfotase alfa were administered to an infant patient with hypophosphatasia who lacked apparent severe clinical symptoms. The results demonstrate the potential feasibility of a tailored therapeutic option based on clinical severity in patients with hypophosphatasia.

Lithium can cause hyperthyroidism as well as hypothyroidism: A systematic review of an under-recognised association

2019 ◽  
Vol 53 (5) ◽  
pp. 384-402 ◽  
Author(s):  
Fiona Fairbrother ◽  
Nicola Petzl ◽  
James G Scott ◽  
Steve Kisely
Keyword(s):  
Cohort Studies ◽  
Clinical Symptoms ◽  
Case Reports ◽  
Lithium Treatment ◽  
Affective State ◽  
Case Series ◽  
Case Control ◽  
Lithium Therapy ◽  
Clinical Implications ◽  
Cross Sectional

Objective: Hypothyroidism is a well-documented consequence of lithium treatment. Less well known is a possible association between lithium therapy and hyperthyroidism. This may have clinical implications as rapid changes in thyroid hormones may worsen a person’s affective state, while symptoms of hyperthyroidism can mimic those of mania. We therefore systematically reviewed the published literature for evidence of lithium-induced hyperthyroidism. Methods: We searched PubMed, Embase and CINAHL for articles where individuals developed biochemically confirmed hyperthyroidism (with or without clinical symptoms), while on lithium therapy for an affective illness. We included case reports, case series, cross-sectional, case control and cohort studies. Results: We included 52 studies, 39 of which were individual case reports and 3 were case series. There were 10 cross-sectional or case control or cohort studies. All the research designs suggested an association between the prescription of lithium and hyperthyroidism. However, these findings were limited by the quality of the included studies, small number of participants and the general lack of either a clear temporal relationship or dose response. Conclusion: Hyperthyroidism is an uncommon side-effect of lithium compared to hypothyroidism but may have clinical implications. However, large prospective studies are required to clarify this association and to further inform the management of patients treated with lithium where hyperthyroidism occurs.

Atypical Manifestations of Severe Acute Respiratory Syndrome Coronavirus 2 Infection in Children: A Review

2021 ◽  
Vol 17 ◽  
Author(s):  
Sofia Βenou ◽  
Shamez Ladhani ◽  
Gabriel Dimitriou ◽  
Despoina Gkentzi
Keyword(s):  
Severe Acute Respiratory Syndrome ◽  
Clinical Symptoms ◽  
Case Reports ◽  
Clinical Manifestations ◽  
Case Series ◽  
Upper Respiratory Infection ◽  
Mild Disease ◽  
Atypical Manifestations ◽  
Novel Coronavirus ◽  
Atypical Presentations

Background: In December 2019, a local outbreak of pneumonia presented in Wuhan (China), and quickly identified to be caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). The disease caused by SARS-CoV-2 was named COVID-19 and was soon declared as pandemic because of the millions of infections and thousands of deaths worldwide. Children infected with SARS-CoV-2 usually develop asymptomatic or mild disease compared to adults. They are also more likely to have atypical and non-specific clinical manifestations than adults. Methods: A literature search was performed in PubMed and Scopus to summarize the extrapulmonary manifestations of SARS-CoV-2 infection in children since the beginning of the pandemic. Peer-reviewed papers in English were retrieved using the following keywords and combinations: ‘pediatric’, ‘child’, ‘infant’, ‘neonate’, ‘novel coronavirus’, ‘SARS-CoV-2’, ‘COVID 19’ and ‘gastrointestinal’, ‘renal’, ‘cardiac’, ‘dermatologic’ or ‘ophthalmologic’. We included published case series and case reports providing clinical symptoms and signs in SARS-CoV2 pediatric patients. Results: Although fever and symptoms of upper respiratory infection are the most frequently presented, a variety of other atypical presentations has also been reported. The clinical spectrum includes dermatological, ophthalmological, neurological, cardiovascular, renal, reproductive, and gastrointestinal presentations. In addition, a rare multi-inflammatory syndrome associated with SARS-CoV-2 infection has been reported in children, often leading to shock requiring inotropic support and mechanical ventilation. Conclusions: Clinicians need to be aware of the wider range of extrapulmonary atypical manifestations of SARS-CoV-2 infection in children, so that appropriate testing, treatment, and public health measures can be implemented rapidly.

Angiomatoid Fibrous Histiocytoma: The Current Status of Pathology and Genetics

2015 ◽  
Vol 139 (5) ◽  
pp. 674-682 ◽  
Author(s):  
Khin Thway ◽  
Cyril Fisher
Keyword(s):  
Fibrous Histiocytoma ◽  
Case Reports ◽  
Correct Diagnosis ◽  
Molecular Genetic ◽  
Case Series ◽  
Current Status ◽  
Gene Fusions ◽  
Soft Tissue Neoplasm ◽  
Medical Databases ◽  
Angiomatoid Fibrous Histiocytoma

Context Angiomatoid fibrous histiocytoma (AFH) is a rare soft tissue neoplasm of intermediate biologic potential and uncertain differentiation, most often arising in the superficial extremities of children and young adults. While it has characteristic histologic features of nodular distributions of ovoid and spindle cells with blood-filled cystic cavities and a surrounding dense lymphoplasmacytic infiltrate, there is a significant morphologic spectrum, which coupled with its rarity and lack of specific immunoprofile can make diagnosis challenging. Angiomatoid fibrous histiocytoma is associated with 3 characteristic gene fusions, EWSR1-CREB1 and EWSR1-ATF1, which are also described in other neoplasms, and rarely FUS-ATF1. Angiomatoid fibrous histiocytoma is now recognized at an increasing number of sites and is known to display a variety of unusual histologic features. Objective To review the current status of AFH, discussing putative etiology, histopathology with variant morphology and differential diagnosis, and current genetics, including overlap with other tumors harboring EWSR1-CREB1 and EWSR1-ATF1 fusions. Data Sources Review of published literature, including case series, case reports, and review articles, in online medical databases. Conclusions The occurrence of AFH at several unusual anatomic sites and its spectrum of morphologic patterns can result in significant diagnostic difficulty, and correct diagnosis is particularly important because of its small risk of metastasis and death. This highlights the importance of diagnostic recognition, ancillary molecular genetic confirmation, and close clinical follow-up of patients with AFH. Further insight into the genetic and epigenetic changes arising secondary to the characteristic gene fusions of AFH will be integral to understanding its tumorigenic mechanisms.

Cannabis-associated arteritis

VASA ◽  
2010 ◽  
Vol 39 (1) ◽  
pp. 43-53 ◽  
Author(s):  
Grotenhermen
Keyword(s):  
Systematic Review ◽  
Case Reports ◽  
Case Series ◽  
Cardiovascular Effects ◽  
Causative Factor ◽  
Cannabis Use ◽  
Thromboangiitis Obliterans ◽  
Pathological Features ◽  
Scientific Support ◽  
Clinical And Pathological Features

Background: To investigate the hypothesis that cases of arteritis similar to thromboangiitis obliterans (TAO) and associated with the use of cannabis were caused by cannabis or THC (dronabinol), or that cannabis use is a co-factor of TAO. Patients and methods: A systematic review on case reports and the literature on so-called cannabis arteritis, TAO, and cardiovascular effects of cannabinoids was conducted. Results: Fifteen reports with 57 cases of an arteritis associated with the use of cannabis and two additional case series of TAO, in which some patients also used cannabis, were identified. Clinical and pathological features of cannabis-associated arteritis do not differ from TAO and the major risk factor of TAO, tobacco use, was present in most, if not in all of these cases. The proposed pathophysiological mechanisms for the development of an arteritis by cannabis use are not substantiated. Conclusions: The hypothesis of cannabis being a causative factor or co-factor of TAO or an arteritis similar to TAO is not supported by the available evidence. The use of the term “cannabis arteritis” should be avoided until or unless more convincing scientific support is forthcoming.

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