HDR syndrome: a follow-up genotype-phenotype analysis of a de novo missense Thr272Ile mutation in exon 4 of GATA3.

Hypoparathyroidism, sensorineural deafness and renal dysplasia (HDR) syndrome (MIM 146255) is a rare autosomal dominant disorder caused by mutations in the gene encoding GATA3, a dual zinc-finger transcription factor involved in vertebrate embryonic development. In this clinical case study we report on a follow-up of a phenotype associated with a GATA3 mutation. HDR syndrome was clinically diagnosed at age of 1.5 years in a boy with a de novo heterozygous missense (c.815C→T) mutation, Thr272Ile, in exon 4 of the GATA3 gene. Both parents were negative for Thr272Ile.At age of 17 months, the patient had a weight of 10.7, a body length of 78 cm, and a head circumference of 47.5 cm. By the age of 7 years, growth is age-appropriate, severe bilateral hearing loss (dB 60) was corrected by hearing aids. However, cognitive development (auditory sensory me-mory and language abilities) is at the lower ends of the test scores.In conclusion, a mildly impaired clinical course was achieved by the age of 7 years in a patient with HDR syndrome; this report adds to the body of data on genotype-phenotype analysis in HDR syndrome. ·

X-linked chronic granulomatous disease (CGD) caused by an intra-exonic splice mutation (CYBB exon 3, c.262G->A) is mimicking juvenile sarcoidosis.

BACKGROUND: Chronic granulomatous disease (CGD) is caused by mutations in genes encoding nicotinamide dinucleotide phosphate (NADPH) oxidase subunits. CASE REPORT: A boy was diagnosed as having juvenile sarcoidosis because he presented with cervical and pulmonary lymphadenopathy with epitheloid cells and granuloma formation and high angiotensin converting enzyme. Later, a liver abscess was diagnosed. CGD was established by a dihydrorhodamine 123 (DHR) assay and genetic analysis revealed an unusual intra-exonic splice mutation in the CYBB gene encoding gp91-phox. It did not change the amino acid sequence and allowed for residual NADPH oxidase activity explaining the late onset of the disease. CONCLUSION: CGD is an important differential diagnosis of juvenile sarcoidosis.

An approach to study the viral safety of plasma-derived products in previously treated, non-infected patients.

Using the polymerase chain reaction (PCR), we designed a study concept to evaluate the safety of plasma derivatives in previously treated patients who are non-infected by the specific viruses studied. Several product lots can be studied in a single patient, with a study period for each lot of 3 months. In the present study 19 patients were included for treatment with Baxter Hyland Immuno's PCR-screened factor VIII concentrate Immunate (n=7), factor IX concentrate Immunine (n=10), the by-passing agent FEIBA plus Immunine (n=1), and the protein C concentrate Ceprotin (n=1). PCR testing for hepatitis B, C or HIV genomic material in patient samples was done as well as serological testing. All patients remained negative for the tested markers. All seven Immunate patients completed three treatment periods with three different lots of the study drug. The median study period was 282 days and the median dose 115 000 units, with a median of 115 exposure days. Five of the 10 Immunine patients completed three treatment periods and four patients, two treatment periods. One Immunine patient was discontinued from the study for reasons unrelated to the study drug administration. The median study period was 305 days and the median total dose 82 200 units, with a median of 88 exposure days. Our study presents a new design to approach the evaluation of viral safety of new plasma derivatives in previously treated, non-infected patients (NIPs) and offers several advantages over the currently recommended studies using testing for serological markers of infection in previously untreated patients (PUPs).

[Neurocysticercosis in an 8-year-old girl]. / Neurozystizerkose bei einem 8jährigen Mädchen.

We report about an 8-year-old girl with signs of elevated intracranial pressure. X-ray, CT and MRT scan showed an inner hydrocephalus as well as an intracranial calcification. By western blot analysis a Taenia solium cysticercosis could be diagnosed. In spite of spontaneous remission of the symptoms we treated with Praziquantel. Resection of the cyst was not necessary. Diagnostic and therapeutic problems of cysticercosis are discussed.

Bare lymphocyte syndrome--combined immunodeficiency and neutrophil dysfunction.

A 4-year-old girl presented with recurrent infections. Immunoglobulin deficiency (serum and secretory IgA, serum IgG3) neutropenia and neutrophil dysfunction (defective spontaneous migration and chemotaxis) were found. T-lymphocyte counts were normal and they responded to phytohaemagglutinin but were not stimulated by Concanavalin A, pokeweed mitogen and microbial antigens in vitro. Delayed cutaneous hypersensitivity testing to purified protein derivative and candidin was negative. Despite bacille Calmette-Guérm vaccination and candidiasis, near normal beta-2-micro-globulin and human leucocyte antigen (HLA) class I concentrations were detected on mononuclear cells and phytohaemagglutinin-induced lymphoblasts. HLA class II antigens (HLA-DP, -DQ, -DR) were not expressed. These observations indicated a bare lymphocyte syndrome (BLS) type II. This is the first time neutrophil dysfunction has been noted in association with BLS.

Clinical course of an exacerbated pulmonary infection in a girl with cystic fibrosis (CF).

The treatment of severe pulmonary infection in young CF-adults depends on age, clinical course, bacterial colonization of the lung, susceptibility pattern and state of nutrition. Besides specific antibiotic therapy, enzyme replacement and physiotherapy, high caloric nutrition, continuous oxygen insufflation and early mobilisation are the main tools in the treatment of an exacerbated pulmonary infection with respiratory insufficiency.

Determination of chymotrypsin in stool by a new photometric method.

A photometric method to determine chymotrypsin in stool, equivalent to the titrimetric analysis, was developed. The chymotrypsin concentrations found in healthy children and those with gastrointestinal and pancreatic disease permit the same clinical conclusions as the titrimetrically determined results. In view of its lower technical requirements, this method is suitable for the identification of maldigestion in pediatric and general practice.

[Determination of chymotrypsin in the feces by a new photometric method]. / Bestimmung des Chymotrypsins im Stuhl mit einer neuen photometrischen Methode.

Fecal chymotrypsin (FCT) was determined in stool specimens of healthy children and those with gastro-intestinal disease, by a new photometric method. The values are comparable with chymotrypsin concentrations found by pH-stat method. The new test is cheap, reliable and easy to perform. For this reasons and for the sensitivity of all tubeless pancreatic function tests (NBT-PABA, FDL, FCT) is rather low (60-70%), the FCT-test may be preferred as diagnostic marker for differential diagnosis of exocrine pancreatic insufficiency.

[Immunoreactive trypsin in the serum of normal children and children with gastrointestinal diseases]. / Immunreaktives Trypsin im Serum gesunder Kinder und solcher mit gastrointestinalen Erkrankungen.

Serum immunoreactive trypsin (IRT) was measured in cord blood and blood specimens of 156 healthy children of different age. These results were compared with the IRT of children with gastrointestinal disease. While IRT from newborn is significantly elevated, mean trypsin levels form older children do not differ from those found in adults. In acute pancreatitis too, as in renal failure, trypsin is elevated. Low trypsin values were estimated in acute hepatitis and Crohn's disease. In cystic fibrosis (CF) serum trypsin levels depend on the exocrine function of the pancreas. The IRT assay on dried blood-spots, seems to become a reliable and convenient neonatal screening test for CF in newborns.

[Erythrocyte enzymes and 2,3-diphosphoglycerate in juvenile diabetics]. / Erythrozytenenzyme und 2,3-Diphosphoglycerat bei juvenilem Diabetes.

The activity levels of phosphoglyceromutase, Glucose-6-P-dehydrogenase. 3-P-Glyceratkinase and Glutathionreductase of the erythrocytes as well as 2,3-Diphosphoglycerate were determined in a total of 263 children suffering from juvenile diabetes mellitus. They were divided into two groups: 103 diabetics with a good state of metabolic control and 103 diabetics with a bad control. The results of 57 diabetic children were rejected. The enzyme activities have been shown to vary. PGM activity was increased in all diabetics, G-6-PDH only in such with bad condition of metabolic control. The activity of 3-PGK was significantly diminished, Glutathionreductase activity was indifferent in both groups. Until today we don't found results of other authors determining these enzymes. The changes of some enzyme activities in diabetics may be due to hormonal mechanisms by insulin.

[Trypsin deficiency in diabetes mellitus of children and adolescents (author's transl)]. / Trypsinmangel bei Diabetes mellitus im Kindes- und Jugendlichen Alter.

In 111 children and juveniles aged 7--27 years suffering from insulin-dependent diabetes mellitus the immunoreactive plasma human pancreatic trypsin was measured by means of the method RIAGnost-Trypsin-test, Behring. Decreased plasma trypsin was measured at the onset of diabetes already. In patients with diabetes with a period of 8--13 years the trypsin values were found to be significantly lower (79.6 +/- 35.3 ng/ml) than in these suffering from diabetes 0--3 years (100,4 +/- 36.9 ng/ml). None of all these patients had clinical pancreatic disease. Abnormalities in exocrine pancreatic function occur in patients with insulin-dependent diabetes mellitus, which is not confined to pancreatic islets only. Until today clinical consequences not can be drawn.

Determination of protease-cleaved p-aminobenzoic acid (PABA) in serum after oral administration of N-benzoyl-L-tyrosyl-p-aminobenzoic acid (PABA-peptide) in children.

A modification of the urine PABA tet published by Imondi et al. is described. Ninety minutes after oral administration of PABA peptide, PABA was determined in serum. The average concentration in healthy children was 0.42 +/- 0.055 mg per 100 ml. Up to that time we recovered in the urine 66.1 +/- 6.1% of the substance previously administered. In the children with cystic fibrosis of the pancreas (CF) serum PABA concentrations were less than 0.1 mg per 100 ml. The infants under 2 months old also had clearly low serum concentrations, on average 0.29 +/- 0.06 mg per 100 ml, whereas the PABA concentrations in the older babies lay within the range for the older children (0.40 +/- 0.07 mg%).

[Examination of pancreatic function in children with special reference to the PABA-test (author's transl)]. / Pankreasfunktionsdiagnostik, insbesondere PABA-Test, im Kindesalter.

To establish the diagnosis of acute pancreatitis the estimation of amylase in serum and urine, lipase and radio-immunoreactive trypsin in the serum are useful. Lipase estimations are more helpful than measuring amylase values. Trypsin-RIA-tests are increasingly important adults. But in chronic pancreatitis and inborn secretory insufficiencies of the pancreas these methods are less helpful. PABA-test, pancreolauryl-test (PLT), and the estimation of chymotrypsin in faeces are screening procedures, although their results correlate well amongst each other. As compared to the chymotrypsin estimation in faeces PABA test and PLT allow for some semiquantitative estimation of the secretory function and dynamics of the gland. The influence of malabsorption, liver and kidney diseases on these parameters is not yet quite clarified. Besides screening they are undoubtedly of value for judging the course and therapy of cystic fibrosis, Shwachman-syndrome, iatrogenic lesions by cytostatics (immunosuppressives and corticosteroids). Quantitative estimations of fat in faces and the pancreozymin test are no longer of significance.

Distal 2q duplication: report of two familial cases and an attempt to define a syndrome.

Two cases of partial trisomy 2q are described, both resulting from a balanced translocation in one of the parents. In one case the chromosomes 2 and 11 were involved [paternal karyotype: 46,XY,t(2;11)(q33;q23)]; in the second case, chromosomes 2 and 8 [paternal karyotype: 46,XY, t(2;8(q32;p23)]. When the two patients were compared to the few cases reported in the literature, it was concluded that the associated clinical syndrome is characterized by severe psychomotor retardation and relatively mild abnormalities involving skull and facies.