Real-world patient data on immunity and COVID-19 status of patients with MPS, Gaucher, and Pompe diseases from Turkey.

BACKGROUND: COVID-19 and lysosomal storage disorders (LSDs) share a common immunological pathway as they cause the release of cytokines in a similar pattern. We aimed to evaluate the immunity status and reveal the course of COVID-19 in patients with LSDs. RESULTS: The median age of 110 patients with LSDs was 129 months (range: 21-655), and all but one patient with mucopolysaccharidosis (MPS) type III were regularly receiving enzyme replacement therapy (ERT). In 53.6% (n = 56) of the patients (23 patients with Gaucher disease [10 type III, 13 type I], 26 patients with MPS [8 type VI, 11 type IVA, 1 type III, 3 type II, and 3 type I], and 7 patients with Pompe disease), an abnormality in at least one of the autoimmunity or immunodeficiency parameters was reported. Furthermore, 12 (57%) of 21 Gaucher cases (7 type III, 5 type I), 18 (40.9%) of 44 MPS cases (9 type IVA, 5 type VI, 1 type I, 2 type II, and 1 type III), and six (66%) of nine Pompe cases were reported to involve abnormalities in at least one of the parameters related to immunodeficiency. Immunoglobulin (Ig) M and IgA levels were reported to be lower, and there were abnormalities in the lymphocyte counts and subgroups in the MPS group. ANA was reported to be positive in one patient with Gaucher type III, anti-DNA in two patients with Gaucher type I and one patient with MPS type VI, antithyroglobulin in two patients with Gaucher type I, anti-TPO in one patient with Gaucher type I, TRAB in one patient with Gaucher type I, antiphospholipid IgM in three patients with Gaucher type III and one patient with Gaucher type I, anticardiolipin IgM in one patient with Gaucher type I, one patient with Gaucher type III, and one patient with MPS type II. However, no clinical presentation was consistent with the laboratory results except for one patient with Gaucher type I disease with Hashimoto thyroiditis. Two of the four patients who survived the COVID-19 infection with mild symptoms had a diagnosis of Gaucher type I, and no abnormality was detected in their laboratory tests. The other two patients had a diagnosis of MPS types VI and II. Immune dysfunction was detected in the patient with a diagnosis of MPS type II. Four of our patients were discharged without any sequelae. CONCLUSION: Problems with immunity did not cause any noticeable clinical results. Being well protected by reducing social contact might have played a role. However, we believe that it should be borne in mind that cardiac and pulmonary involvement, as well as immune dysfunction in LSDs, may cause an increased need for intensive care because of secondary bacterial infections.

Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene

Background: X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. We aimed to analyze the clinical, immunological and genetic characteristics of 22 male children with XLA. Methods: Twenty-two children with XLA from 12 unrelated families were enrolled in this study. Clinical and demographic features of patients, serum immunoglobulin levels, percentage of B cells and BTK gene mutations were reviewed retrospectively. Results: We identified 12 different mutations in 22 patients from 12 unrelated families. The most frequent type of mutation was premature stop codon (33.3%). Ten mutations had been reported previously including three missense mutations (c.1774T>C, c.1684C>T, c.83G>T), three premature stop codons (c.1558C>T, c.1573C>T, c.753G>A), two splice-site (c.683-1G>A, c.1567-12_1567-9delTTTG) and two small nucleotide deletions (c.902-904_delAAG, c.179_181delAGA). Two novel mutations of the BTK gene were also presented and included one splice-site mutation (c.391+1G>C) and one premature stop codon mutation (c.1243_1243delG). Six out of 12 mutations of the BTK gene were located in the SH1 domain, two in the PH domain, two in the SH3 domain and two in the SH2 domain. Three patients had a history of severe infection before diagnosis. We did not identify any correlation between severity of clinical symptoms and the genotype. Conclusions: Our results show that mutations in southeast Turkey could be different from those in the rest of the world and molecular genetic tests are an important tool for early confirmed diagnosis of XLA

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Clinical and genetic profiles of patients with X-linked agammaglobulinemia from southeast Turkey: Novel mutations in BTK gene.

BACKGROUND: X-linked agammaglobulinemia (XLA) is characterized by absent or severely reduced B cells, low or undetectable immunoglobulin levels, and clinically by extracellular bacterial infections which mainly compromise the respiratory tract. We aimed to analyze the clinical, immunological and genetic characteristics of 22 male children with XLA. METHODS: Twenty-two children with XLA from 12 unrelated families were enrolled in this study. Clinical and demographic features of patients, serum immunoglobulin levels, percentage of B cells and BTK gene mutations were reviewed retrospectively. RESULTS: We identified 12 different mutations in 22 patients from 12 unrelated families. The most frequent type of mutation was premature stop codon (33.3%). Ten mutations had been reported previously including three missense mutations (c.1774T>C, c.1684C>T, c.83G>T), three premature stop codons (c.1558C>T, c.1573C>T, c.753G>A), two splice-site (c.683-1G>A, c.1567-12_1567-9delTTTG) and two small nucleotide deletions (c.902-904_delAAG, c.179_181delAGA). Two novel mutations of the BTK gene were also presented and included one splice-site mutation (c.391+1G>C) and one premature stop codon mutation (c.1243_1243delG). Six out of 12 mutations of the BTK gene were located in the SH1 domain, two in the PH domain, two in the SH3 domain and two in the SH2 domain. Three patients had a history of severe infection before diagnosis. We did not identify any correlation between severity of clinical symptoms and the genotype. CONCLUSIONS: Our results show that mutations in southeast Turkey could be different from those in the rest of the world and molecular genetic tests are an important tool for early confirmed diagnosis of XLA.

Common features of anaphylaxis in children

Objective: We aimed to establish the characteristics of anaphylaxis in childhood. Methods: Forty-four patients who had experienced anaphylaxis in a period of 10 years (from 1999 to 2009), were included in the study. Parameters analysed were age, gender, concomitant allergic disease, trigger, setting, clinical symptoms, treatment, prognosis and prophylaxis. Results: The total numbers of anaphylaxis cases were 44 in a ten-year period. The ages of patients ranged from 3 to 14 years (11.50 ± 3.87 years) and the majority were male. 33 of the patients (75%) had a concomitant allergic disease. The trigger was determined in 93.2% of the cases, being most frequent: food (27.3%), and SIT (25%), followed by bee sting, medications and others. Respiratory (95.5%), dermatological (90.9%), cardiovascular (20.5%), neuropsychiatric (25%), and gastrointestinal (11.4%) symptoms were seen most frequently. For anaphylaxis triggered by food, the duration of anaphylactic episode was significantly longer (p < 0.05). No biphasic reaction was observed during these attacks. Of our patients, only one developed respiratory failure and cardiac arrest due to SIT, and intensive care support was required. Discussion: As a trigger for anaphylaxis, the frequency of SIT is so high that it cannot be described by the study group including patients who were followed up in an outpatient allergy clinic (AU)

Common features of anaphylaxis in children.

OBJECTIVE: We aimed to establish the characteristics of anaphylaxis in childhood. METHODS: Forty-four patients who had experienced anaphylaxis in a period of 10 years (from 1999 to 2009), were included in the study. Parameters analysed were age, gender, concomitant allergic disease, trigger, setting, clinical symptoms, treatment, prognosis and prophylaxis. RESULTS: The total numbers of anaphylaxis cases were 44 in a ten-year period. The ages of patients ranged from 3 to 14 years (11.50 ± 3.87 years) and the majority were male. 33 of the patients (75%) had a concomitant allergic disease. The trigger was determined in 93.2% of the cases, being most frequent: food (27.3%), and SIT (25%), followed by bee sting, medications and others. Respiratory (95.5%), dermatological (90.9%), cardiovascular (20.5%), neuropsychiatric (25%), and gastrointestinal (11.4%) symptoms were seen most frequently. For anaphylaxis triggered by food, the duration of anaphylactic episode was significantly longer (p<0.05). No biphasic reaction was observed during these attacks. Of our patients, only one developed respiratory failure and cardiac arrest due to SIT, and intensive care support was required. DISCUSSION: As a trigger for anaphylaxis, the frequency of SIT is so high that it cannot be described by the study group including patients who were followed up in an outpatient allergy clinic.