Fatal Neonatal DOLK-CDG as a Rare Form of Syndromic Ichthyosis

Neonatal collodion baby or ichthyosis can pose a diagnostic challenge, and in many cases, only additional organ involvement or the course of the disease will help differentiate between non-syndromic and syndromic forms. Skin abnormalities are described in about 20% of the congenital disorders of glycosylation (CDG). Among those, some rare CDG forms constitute a special group among the syndromic ichthyoses and can initially misdirect the diagnosis towards non-syndromic genodermatosis. DOLK-CDG is such a rare subtype, resulting from a defect in dolichol kinase, in which the congenital skin phenotype (often ichthyosis) is later associated with variable extracutaneous features such as dilatative cardiomyopathy, epilepsy, microcephaly, visual impairment, and hypoglycemia and may lead to a fatal course. We report two neonatal cases of lethal ichthyosis from the same family, with distal digital constrictions and a progressive course leading to multi-organ failure and death. Postmortem trio whole-exome sequencing revealed the compound heterozygous variants NM_014908.3: c.1342G>A, p.(Gly448Arg) and NM_014908.3: c.1558A>G, p.(Thr520Ala) in the DOLK gene in the first affected child, which were confirmed in the affected sibling. Reduced staining with anti-α-Dystroglycan antibody was observed in frozen heart tissue of the second child as an expression of reduced O-mannosylation due to the dolichol kinase deficiency. In addition to the detailed dermatopathological changes, both cases presented hepatic and extrahepatic hemosiderosis on histological examination. Our patients represent an early and fatal form of DOLK-CDG with a striking presentation at birth resembling severe collodion baby. Both cases emphasize the phenotypic variability of glycosylation disorders and the importance to broaden the differential diagnosis of ichthyosis and to actively search for organ involvement in neonates with ichthyosis.

Ecthyma Gangrenosum in a Pediatric Patient and Review of the Literature

Erythema Gangrenosum (EG), is an infective lesion of skin, and mucous membranes typically occurring in patients with chronic disease or immunocompromised patients. İt is a very rarely seen vasculitis with a potentially progressive and fatal course. An 8-year-old pediatric patient was referred to an external medical center with complaints of fever, abdominal pain, and skin rashes starting 2 days previously, and upon deterioration of his general health state, he was admitted into a surgical intensive care unit with manifestations of septic shock. In the treatment, all necrotic tissues including skin, and subcutaneous tissue were excised down to a healthy tissue after excision of all necrotic tissue. Vacuum Assisted Closure (VAC) was applied on this area for drainage. Herein, we aimed to indicate that definitive treatment of a neuropathic child with EG is surgery excision, and also emphasize critical importance of re-excision of newly developed necrotic tissue at an early stage, and close monetarization of the patient

High viral loads: what drives fatal cases of COVID-19 in vaccinees? – an autopsy study

BackgroundThe rate of SARS-CoV-2 breakthrough infections in vaccinees is becoming an increasingly serious issue.ObjectiveTo determine the causes of death, histological organ alteration, and viral spread in relation to demographic, clinical-pathological, viral variants, and vaccine types.DesignComprehensive retrospective observational cohort study. Setting: Consecutive cases from four German academic medical centers.PatientsDeceased with proven SARS-CoV-2 infection after vaccination who died between January and November 2021. Collections of 29 vaccinees which were analyzed and compared to 141 nonvaccinated control cases.ResultsAutopsies were performed on 16 partially and 13 fully vaccinated individuals. Most patients were elderly and suffered from several relevant comorbidities. Real-time RT-PCR (RT-qPCR) identified a significantly increased rate of generalized viral dissemination within the organism in vaccinated cases versus nonvaccinated cases (45% vs. 16%, respectively; P = 0.008). Vaccinated cases also showed high viral loads, reaching Ct values below 10, especially in the upper airways and lungs. This was accompanied by high rates of pulmonal bacterial or mycotic superinfections and the occurrence of immunocompromising factors such as malignancies, immunosuppressive drug intake, or decreased immunoglobulin levels. All these findings were particularly accentuated in partially vaccinated patients compared to fully vaccinated individuals. A fatal course after vaccination occurred in only 14% of all COVID-19 deceased in Augsburg.LimitationsRestricted number of casesConclusionsFatal cases of COVID-19 in vaccinees were rare and often associated with severe comorbidities or other immunosuppressive conditions. Interestingly, we observed striking virus dissemination in our case study, which may indicate a decreased ability to eliminate the virus in patients with an impaired immune system. However, the potential role of antibody-dependent enhancement must also be ruled out in future studies.Funding sourceThis work was supported by the German Registry of COVID-19 Autopsies (www.DeRegCOVID.ukaachen.de) and funded by the Federal Ministry of Health (ZMVI1-2520COR201), the Federal Ministry of Education and Research within the framework of the network of university medicine (DEFEAT PANDEMICs, 01KX2021), and the German Federal Ministry of Food and Agriculture through the Federal Office for Agriculture and Food (project ZooSeq, grant number 2819114019).

Staphylococcal Epidermolysis: A Case Report

Acute staphylococcal epidermolysis, also known as staphylococcal scalded skin syndrome (SSSS), in young children is caused by the release of exfoliative toxins A and B (ETA and/or ETB) from an initial outbreak which can be ear-nose-throat, conjunctival or cutaneous. Staphylococcal scalded skin syndrome is characterized by painful erythroderma, quickly followed by generalized detachment with respect to mucous surfaces, regressing in 2 to 4 days on antibiotics. The positive diagnosis is mainly based on clinical examination and sometimes on skin biopsy. The course of the disease is benign, favored by anti-staphylococcal treatment combined with local care. However, the risk of fatal course is estimated at around 4% in the event of delay in antibiotic treatment. We report the case of an infant with SSSS, diagnosed and treated early with good evolution.

Fatal Course of Cutaneous Cholesterol Embolization Syndrome: A Case Report

Cholesterol embolization syndrome is an increasing but underestimated problem after endovascular intervention or after the start of thrombolytic therapies. Embolies from the aortic wall involves abdominal organs and the skin of the lower extremities or buttocks. In our case a progressive ulceration and necroses occurs spontaneously. Endovascular treatment of the lower extremities was successful for a short period. Due to the progression of necrosis, both legs were amputated. Biopsies were taken from the skin were initially no directions to the diagnosis of Cholesterol embolization syndrome. After a second elliptical excision biopsy the diagnosis of cholesterol embolization syndrome was confirmed. Because the rapid progression of skin necroses despite the treatment of prednisone, patient died due to sepsis and renal failure. This case shows when arterial revascularization is performed and progression in skin necrosis occurs despite optimal arterial vascular status the diagnosis CES should be considered and treated in an early state of disease.

Fatal course of undetected Ewing-like sarcoma in a 9-year-old boy with uncharacteristic clinical presentation

A 9-year-old boy collapsed shortly after complaining of shortness of breath. Despite immediate resuscitation measures, the boy died. A few weeks earlier, he had received antibiotic treatment for respiratory infection. However, the post-mortem examination revealed an advanced tumor mass of the mediastinum with infiltration of vital structures, which was identified as a small blue round neoplasm with aspects of an extramedullary Ewing-like sarcoma by supplementary histological and immunohistochemical examinations.This dramatic clinical course of events shows that the possible presence of serious diseases should always be considered behind harmless symptoms, even in children.

COVID-19-associated multisystem inflammatory syndrome in children: Experiences of three centres in Turkey

ABSTRACT Background The pathogenesis and clinical manifestations of the multisystem inflammatory syndrome in children (MIS-C) has not yet been fully elucidated and there is no clear consensus on its treatment yet. Objectives To evaluate our patients diagnosed with MIS-C and present them to the literature in order to contribute to the better understanding of this new disease, which entered paediatric practice with the SARS-CoV-2 peak. Methods In this study, 17 MIS-C cases diagnosed according to the Centers for Disease Control and Prevention criteria were included. Results Of the patients, 7 (41.2%) had a comorbidity. Gastrointestinal system involvement was the most prominent in the patients (70.6%). Laparotomy was performed in 3 patients due to acute abdomen. Two patients had neurological involvement. Of the patients, 15 (88.2%) received intravenous immunoglobulin and 13 (76.5%) received both intravenous immunoglobulin and methylprednisolone. Two patients received invasive mechanical ventilation and 4 patients received high flow rate nasal cannula oxygen therapy. One of our patients who needed invasive mechanical ventilation and high vasoactive-inotrope support died despite all supportive treatments including plasmapheresis and extracorporeal membrane oxygenation. Conclusions MIS-C picture can have a fatal course and may present with severe gastrointestinal and neurological signs. Unnecessary laparotomy should be avoided.

Spondylometaepiphyseal Dysplasia Short Limb-Abnormal Calcification Type in Turkish Patients Reveals a Novel Mutation and New Features

Spondylometaepiphyseal dysplasia short limb-abnormal calcification type (SMED-SL/AC) is a rare autosomal recessive disorder. It is a severe dwarfism syndrome with a characteristic feature of progressive calcification of epiphyseal and other cartilaginous tissues. It is caused by pathogenic variants in the <i>DDR2</i> gene encoding the discoidin domain receptor tyrosine kinase 2. Thus far, 37 cases and 8 pathogenic variants have been reported. Most of the reported cases are of Middle Eastern and Puerto Rican origins. Only one Turkish case has been reported previously with a novel truncating variant p.(R489*). Here, we report 2 new cases, 1 with a novel variant p.(S311G) and 1 with a splice site variant c.2283+1G&#x3e;A. In addition, we reviewed a previously reported case, and sequencing of stored DNA revealed the recently reported nonsense variant p.(R489*) as the underlying cause. Therefore, our data increase the number of SMED-SL/AC Turkish patients with molecular results to 4. Furthermore, we compared the features of Turkish patients with other reported cases and expanded the characteristics of the disorder with new features such as triventricular hydrocephalus, intracranial hemorrhage, hypopigmentation of hair, dry and scaly skin, arthralgia, and hypocalcemia. We also compared the pathogenic variants of Turkish patients with other variants, aiming to explain the mechanism leading to a more severe and early fatal course in Turkish patients.

First successful concomitant therapy of immune tolerance induction therapy and desensitization in a CRIM-negative infantile Pompe patient

Objectives Enzyme replacement therapy (ERT) with alglucosidase alfa (rhGAA) has changed the fatal course of infantile Pompe disease, however, development of anti rhGAA antibodies and infusion-associated reactions (IAR) restrict the tolerability and effectiveness of the treatment. Case presentation We describe a successful concomitant immune tolerance induction (ITI) and desensitization protocols in a cross-reactive immunologic material (CRIM) negative 7-month-old male patient. At the age of 5 months and eighth dose of the ERT, the patient developed IAR and his rhGAA specific IgE was negative however, his rhGAA specific IgG titer was as high as 12,800. ITI therapy to suppress antibody formation and a desensitization protocol was devised to be given concomitantly. At the end of 5-week therapy, his fatigue and weakness improved profoundly and a control antidrug antibody level decreased at 800. At the time of the patient’s follow up, he was still on ERT with desensitization at the age of 15 months without any reactions. Conclusions This is the first report in the literature applying concomitant ITI and desensitization protocols in a CRIM negative infantile-onset Pompe disease patient successfully, hence the importance of the case.