7th Drug hypersensitivity meeting: part two

No abstract availabl

Improved metabolic control in tetrahydrobiopterin (BH4), responsive phenylketonuria with sapropterin administered in two divided doses vs. a single daily dose

PubMedID: 28593914Background: Phenylketonuria (PKU) often requires a lifelong phenylalanine (Phe)-restricted diet. Introduction of 6R-tetrahydrobiopterin (BH4) has made a huge difference in the diets of patients with PKU. BH4 is the co-factor of the enzyme phenylalanine hydroxylase (PAH) and improves PAH activity and, thus, Phe tolerance in the diet. A limited number of published studies suggest a pharmacodynamic profile of BH4 more suitable to be administered in divided daily doses. Methods: After a 72-h BH4 loading test, sapropterin was initiated in 50 responsive patients. This case-control study was conducted by administering the same daily dose of sapropterin in group 1 (n=24) as a customary single dose or in two divided doses in group 2 (n=26) over 1 year. Results: Mean daily consumption of Phe increased significantly after the first year of BH4 treatment in group 2 compared to group 1 (p<0.05). At the end of the first year of treatment with BH4, another dramatic difference observed between the two groups was the ability to transition to a Phe-free diet. Eight patients from group 2 and two from group 1 could quit dietary restriction. Conclusions: When given in two divided daily doses, BH4 was more efficacious than a single daily dose in increasing daily Phe consumption, Phe tolerance and the ability to transition to a Phe-unrestricted diet at the end of the first year of treatment. © 2017 Walter de Gruyter GmbH, Berlin/Boston

Immediate and late onset forms of insulin hypersensitivity presenting with glucose dysregulation [Glukoz disregülasyonu ile ortaya çikan erken ve geç başlangiçli ınsulin aşiri duyarliliği]

We report the case of a 35-year-old woman allergic to detemir, neutral protamine Hagedorn, and glargine. Initially, local reactions to the insulin preparations occurred, which continued even after the types of insulin and the application areas were changed. When the use of insulin therapy was continued, the local reactions developed into systemic forms. Interestingly, blood glucose levels kept increasing to uncontrolled levels every time the cutaneous reactions occurred. The patient was referred to our clinic for further investigation. The results of the skin prick tests with insulin preparations were negative; however, the intradermal test results were positive with the following dilutions of the insulin preparations: 1/100 detemir, 1/100 glargine, 1/1.000 neutral protamine Hagedorn, and 1/1.000 regular insulin. The intradermal skin test results for glulisine, aspart, and lispro were negative. The levels of immunglobulin E specific to human insulin were high (194 kU/L; N 0-87 kU/L); whereas, the specific immunglobulin G4 levels were normal (35 mg/dL; N 0-125 mg/dL). We attempted to treat the patient with glulisine and aspart; however, similar reactions were observed with these insulin preparations as well. As we considered the levels of the anti-insulin antibodies and the late-onset local reactions, the insulin allergy in our patient was reckoned to be mediated by Type 1 and Type 4 hypersensitivity. The only insulin preparation that had never been used with this patient before was lispro, which also demonstrated negative intradermal skin test results. Therefore, we suggested the use of a continuous subcutaneous insulin infusion pump with lispro. Finally, the insulin hypersensitivity was successfully treated, and glycemic control was achieved. © 2018 by Turkish Journal of Endocrinology and Metabolism Association

Coexistence of 2 rare autosomal recessively inherited disorders manifesting with immune deficiency; IL-12 receptor ß1 and biotinidase deficiencies

PubMedID: 30968642In this report, we described an infant with both partial biotinidase and IL-12Rß1 deficiencies as these two entities are rare and unrelated inherited disorders. One-month-old girl was diagnosed as partial biotinidase deficiency with newborn screening programme. Mutation analysis revealed a compound heterozygous mutation BTD: c.1330G>C (p.Val444Leu) / c.196_197dupCATC (p.Leu69HisfsTer24). At the age of 6 months, a nodule on her left axilla with purulent discharge was noticed which was related to BCG vaccination. A mutational analysis revealed a homozygous c.783+1G>A mutation on IL-12Rß1 gene. Interferon-gamma and anti-tuberculosis treatment were initiated together and the nodule with purulent discharge regressed dramatically. Here, we want to emphasize consideration of coexistence of two rare autosomal recessively inherited diseases in a patient due to the high rate of consanguinity in our country. © 2018, Turkish Journal of Pediatrics. All rights reserved

An ignored cause of red urine in children: Rhabdomyolysis due to carnitine palmitoyltransferase II (CPT-II) deficiency

PubMedID: 28085674Carnitine palmitoyltransferase II (CPT-II) deficiency is an autosomal recessively inherited disorder involving the ß-oxidation of long-chain fatty acids, which leads to rhabdomyolysis and subsequent acute renal failure. The clinical phenotype varies from a severe infantile form to a milder muscle form. Here, we report a 9-year-old boy referred to our hospital for the investigation of hematuria with a 2-day history of dark urine and malaise. As no erythrocytes in the microscopic examination of the urine and hemoglobinuria were present, myoglobinuria due to rhabdomyolysis was the most probable cause of dark urine. After excluding the other causes of rhabdomyolysis, with the help of metabolic investigations, the patient was suspected to have CPT-II deficiency, the most common cause of metabolic rhabdomyolysis. Our aim in presenting this case is to emphasize considering rhabdomyolysis in the differential diagnosis of dark urine in order to prevent recurrent rhabdomyolysis and renal injury. © 2017 Walter de Gruyter GmbH, Berlin/Boston 2017

Congenital erythropoietic porphyria with erythrodontia: A case report

PubMedID: 30706587Background: The causes for intrinsic tooth discoloration can be separated into two categories as systemic and local. Systemic causes are either genetic or drug-induced effects. The development of dentition can also be affected by a number of systemic factors and metabolic diseases such as porphyria. Congenital erythropoietic porphyria (CEP), also known as Gunther's disease, is a metabolic disease caused by a transformation in the gene that codifies uroporphyrinogen-3 synthesis, leading to porphyrin aggregation in urine, skin, bone, and dentin. Case Report: A 21-month-old girl with erythrodontia was referred to Paediatric Dentistry Department in September 2017. A physical examination revealed blisters on her face, nose, hands, and feet. Laboratory findings showed highly elevated urine total uroporphyrin and total coproporphyrin I and III levels. Next-generation sequencing multigene panel testing for porphyria demonstrated a homozygous c.10C>T (p.L4F) mutation in the UROS gene. For curative therapy, the patient was admitted to the allogeneic bone marrow transplantation program. Conclusion: Congenital erythropoietic porphyria most commonly presents in the first few years of life. Manifestations can include reddish-colored urine, skin blistering, scarring, and erythrodontia. A timely diagnosis can prevent undesirable skin findings of the disease and death due to hematological involvement before a curative allogeneic bone marrow transplantation is performed. © 2019 BSPD, IAPD and John Wiley & Sons A/S. Published by John Wiley & Sons Lt

A desensitization method to maintain enzyme replacement therapy in mucopolysaccharidosis type VI

PubMedID: 27164636[No abstract available

Turkish case of ethylmalonic encephalopathy misdiagnosed as short chain acyl-CoA dehydrogenase deficiency

PubMedID: 29159724Ethylmalonic encephalopathy is a very rare autosomal recessively inherited inborn error of metabolism; characterized by encephalopathy, recurrent petechiae without bleeding diathesis, chronic diarrhea, and orthostatic acrocyanosis. Here, we describe a case of ethylmalonic encephalopathy with late onset neurologic symptoms and a confusing family history of two deceased brothers with the wrong suspicion of short chain acyl-CoA dehydrogenase deficiency. © 2017, Springer Science+Business Media, LLC, part of Springer Nature

Four Gaucher disease type II patients with three novel mutations: a single centre experience from Turkey

PubMedID: 29656334Gaucher disease is the most common lysosomal storage disorder due to glucosylceramidase enzyme deficiency. There are three subtypes of the disease. Neurological involvement accompanies visceral and haematological findings only in type II and type III Gaucher patients. Type II is the acute progressive neuronopathic form which is the most severe and rare subtype. Clinical findings are recognized prenatally or in the first months of life and followed by death within the first two years of age. Among our 81 Gaucher patients, we identified 4 (4,9%) type II patients in our metabolic centre. This rate is significantly higher than the rate reported in the literature (<1%). Three of the patients had novel mutations, one of them was a collodion baby and the other one was mistyped as type III due to its atypical presentation at the beginning and he was treated with ERT for 8 months. In this report, we present our type II Gaucher patients with three novel mutations and one perinatal lethal form with generalized ichthyosis which is a very rare disorder. Additionally, we would like to highlight the phenotypic heterogeneity not only between the subtypes, also even in the same type. © 2018, Springer Science+Business Media, LLC, part of Springer Nature

Impaired glucose tolerance in fanconi-bickel syndrome: Eight patients with two novel mutations

PubMedID: 29624224Fanconi-Bickel syndrome (FBS) is a rare, autosomal recessive disorder of carbohydrate metabolism caused by defects in the facilitative glucose transporter 2 (GLUT2 or SLC2A2) gene. Prominent findings are failure to thrive, renal tubular acidosis, hypoglycemia and postprandial hyperglycemia even mimicking diabetes mellitus. Eight patients from 6 families with FBS were included in this study. c.482_483insC homozygous mutation was detected in six patients from four different families. Mutation analysis of SLC2A2 gene revealed two novel homozygous mutations; c.1069delGinsAATAA and c.575A>G. Standard oral glucose tolerance test with 1.75 g/kg oral glucose was performed in six of the patients who were older than 3-years of age. Impaired glucose tolerance was found in all patients as expected and two of them had overt diabetes. None of the antidiabetic medications were given to them in order to avoid significant hypoglycemia. Beside the conservative treatment, follow up with frequent oral glucose tolerance tests are planned. We report these cases of FBS, as GSD XI is rare, two novel mutations were detected and also to highlight the risk of diabetes mellitus; although there is not a consensus about the treatment. © 2017, Turkish Journal of Pediatrics. All rights reserved