Die β-Aktivität im EEG des Kindes

Zusammenfassung Im Vergleich zu den in der. I. Mitteilung berichteten Merkmalen der -Wellen beim gesunden Kinde werden die Kriterien der abnormen -Aktivität aufgezeigt und folgende Erscheinungsformen bei cerebralen Erkrankungen festgestellt: Generalisierte -Wellen, Paroxysmen bilateral synchroner -Wellengruppen, Herdveränderungen, die sowohl durch das umschriebene Auftreten abnormer -Wellen, wie auch durch das regionale Fehlen physiologischer -Aktivität im Wach-und Schlaf.-EEG gekennzeichnet sein können.Abnorme -Wellen erscheinen neben anderen EEG-Veränderungen bei folgenden Krankheitsgruppen: l. pharmakologischen Intoxikationen, 2. cerebralen Anfallsleiden, 3. entzündlichen Hirnerkrankungen, 4. intracerebralen Blutungs-bzw. Erweichungsherden, 5. vasomotorischer Labilität.Longitudinaluntersuchungen bei cerebralen Erkrankungen (z. B. Meningitis tuberculosa), erbrachten den Nachweis, daß den -Wellen bei abnormer Ausprägung der gleiche Krankheitswert zukommt, wie anderen EEG-Veränderungen.Der diagnostische Wert abnormer -Aktivität wird besonders bei den exogenen Intoxikationen und den intracerebralen Blutungs-und Erweichungsprozessen erkennbar.     

The clinical phenotype of β and δβ thalassemias in Greece

Based on precise evaluation of hematological findings and clinical manifestations, the relationship between genotype and clinical phenotype was studied in 475 Greek patients with and thalassemias. Almost all known genotypes are included in this series, but the most frequent was homozygous ^th high A₂ (71.6%), ^th/^th silent (7.4%), ^th/^oth high F (6.3%) and ^th/^th Dutch (6.3%).In general, the phenotype was related to the genotype, though clinical heterogeneity was detected among patients with the same genotype. The severe type of thalassemia major was most commonly found in homozygous ^th patients mainly of ^o/^o and ^o/⁺ genotypes while homozygous ⁺ patients had milder clinical manifestation. Furthermore a small group of patients, characterized as homozygous ⁺⁺ (HbF<30%) had mild thalassemia intermedia. In addition mild thalassemia intermedia was principally related with homozygous ^oth, and compound heterozygous ^th/^th silent I, and less frequently with other genotypes such as compound heterozygous with ^th/^th Dutch, ^th/^th silent II, ^th/^th high F or Lepore.It was shown that precise genetic characterization and clinical evaluation is of primary importance in predicting the prognosis and formulating the proper treatment for the individual patient with thalassemia.     

Adrenoceptors and the lung: their role in health and disease

- and -Adrenoceptors have each been divided into two subgroups (₁, ₂, ₁ and ₂). The basic mechanisms underlying the adrenoceptor/effector coupling are complex and vary for the -, but not for the -subpopulations. Adrenoceptors of the bronchi and the lung show a special pattern of distribution and response, ensuring that the airway system works as a functionary unit. Dysfunctions of adrenoceptormediated effects have been suggested to contribute to some important paediatric disorders such as hyaline membrane syndrome, wet lung, bronchial asthma, cystic fibrosis, and pertussis. Drugs which act on the adrenergic system influence some of these disorders directly. Further studies applying modern techniques to receptor research are needed in order to clarify the basic mechanisms involved in receptor-mediated lung disorders and the activity of drugs in lung tissue.Abbreviations AC adenylate cyclase - ADP adenosine diphosphate - -R -adrenoceptor - cAMP cyclic adenosine monophosphate - CF cystic fibrosis - GDP guanosine diphosphate - GTP guanosine triphosphate - IAP islet activating protein     

Influence of short- and long-term inhalation of salbutamol on lung function and β2-andrenoceptors of mononuclear blood cells in asthmatic children

Clinical observations have shown that some asthma patients develop tachyphylaxis to -sympathomimetic drugs. As down-regulation of the number of -adrenoceptors in different human tissues after exposure to catecholamines and -adrenergic drugs is well known, we investigated whether a interrelation exists between -adrenoceptor down-regulation and clinically detectable -adrenergic subsensitivity during -sympathomimetic treatment. The following results were obtained: 1. ₂-Sympathomimetic inhalation treatment with salbutamol in therapeutic doses led to a significant downregulation of ₂-adrenoceptors and consecutive cyclic adenosine monophosphate response to isoprenaline. This effect was already detectable after short-term treatment of 3–7 days in 9 asthmatic children. 2. In the long-term study over 6 months, salbutamol inhalation in 12 asthmatic children led to a significant down-regulation of -adrenoceptor binding sites on mononuclear blood cells (MNC) from 1539±91 to 1115±99 after 14 days, remaining in this range thereafter. 3. The mean airway resistance (R_aw) of these 12 patients decreased significantly within 14 days from 8.1±0.8 to 5.7±0.5 cm H₂O/l/s to remain stable throughout the 6 months of salbutamol treatment. The differences in R_aw before and immediately after inhalation of 0.2 mg salbutamol (2 puffs) were unchanged during the study period. It is concluded, that long-term inhalative treatment with salbutamol over a period of 6 months does not result in refractoriness to -adrenergic drugs in the airways of asthmatic children, even though a significant down-regulation of ₂-receptors on peripheral MNC occurs.     

Recurrent,familial Reye-like syndrome with a new complex amino and organic aciduria

Five of 13 siblings from a Jewish-Ashkenazi family suffered from recurrent Reye-like episodes. During attacks, these patients excreted -keto-adipic, -hydroxy-adipic, and -aminoadipic acids, branched-chain keto acids and saccharopine in addition, to lactic, pyruvic, and dicarboxylic acids characteristic of Reye syndrome. The serum concentrations of citrulline and -aminoadipic acid were elevated and carnitine was at the upper limit of the normal range. Serum acetoacetate level was 4–5 times the -hydroxybutyrate level, but the pyruvate/lactate ratio was normal. Notably, plasma ketone bodies were lower than expected from the degree of catabolism. When the patients were symptom-free, no abnormal amino or organic acids in serum or urine were detected. These findings might be interpreted as a functional impairment at three different biochemical sites: fatty acid -oxidation, dehydrogenase complexes of the pyruvic, -ketoglutaric, -ketoadipic, and branched-chain keto acids, and pyruvate carboxylase. We suggest that in this hereditary disorder a toxic substance, exogenously or endogenously derived, interfered at multiple sites in different metabolic pathways.     

Serum carnitine levels in patients with homozygous beta thalassemia: a possible new role for carnitine?

Carnitine (-hydroxy--trimethylaminobutyric acid) facilitates the transfer of activated long-chain fatty acids from the cytoplasm to the mitochondria, the site of their -oxidation. Carnitine deficiency results in a reduced usage of fatty acids in energy production and therefore the appearance of clinical symptoms such as myalgia and muscle weakness. In the present study, serum carnitine levels were measured in 45 children and 20 adults with homozygous beta thalassemia. A decrease in serum carnitine levels (total, free and acyl) was found, without any evidence of disorder in the process of mitochondrial -oxidation. The possible cause of this finding could be related to a reduced hepatic carnitine biosynthesis. Conclusion:In patients with homozygous beta thalassemia, the reduction of serum carnitine levels might play an important role in the appearance of muscular dysfunction. It is possible that l -carnitine administration in these patients might improve or even resolve the aforementioned symptom.     

Histiocytic haemophagocytosis in a patient with Kawasaki disease: Changes in the hypercytokinaemic state

Abstract A 32-month-old Japanese boy exhibited haemophagocytic syndrome (HPS) during the recurrent course of Kawasaki disease. Despite repeated -globulin therapy, he developed cytopenia with marked hepatomegaly and evidence of histiocytic haemophagocytosis in the bone marrow. Serum levels of interferon- and tumour necrosis factor, but not of interleukin-1, increased in parallel with his symptoms. No confirmation was obtained of the association of toxic reactions to the used drugs. No coronary lesions remained as sequelae.Conclusion Cytopenia in Kawasaki disease could herald HPS, and the hypercytokinaemia involved in the two febrile syndromes might be of distinct nature.     

Accumulation of pristanic acid (2, 6, 10, 14 tetramethylpentadecanoic acid) in the plasma of patients with generalised peroxisomal dysfunction

The plasma of some patients with biochemical evidence of a generalised peroxisomal dysfunction (GPD) show greatly increased levels of phytanic acid as well as its -oxidation product, pristanic acid (2, 6, 10, 14-tetramethylpentadecanoic acid). Increased amounts of 14- and 16- carbon branched chain fatty acids are also found in some of these patients. As pristanic acid is present in normal or near-normal amounts in classical Refsum disease and rhizomelic chondrodysplasia, two disorders characterised by deficiencies in phytanic acid oxidation, we speculate that its accumulation is not secondary to a defect in the -oxidation of phytanic acid, but is indicative of a block in the peroxisomal -oxidation of pristanic acid. The finding of phytanic acid, as well as a number of its metabolites in patients with inherited defects in peroxisomal biogenesis indicates that a number of the steps in phytanic acid degradation may be confined to peroxisomes.Abbreviations GPD generalised peroxisomal dysfunction - VLCFA very long chain fatty acids - THCA 3, 7, 12-trihydroxy-5-cholestan-26-oic acid - br branched chain fatty acid - ALD adrenoleukodystrophy - DHAPAT dihydroxyacetone phosphate acyltransferase     

Urinary excretion of 17-hydroxypregnanolones in patients with different forms of congenital adrenal hyperplasia due to steroid 21-hydroxylase deficiency

To improve diagnostic criteria in different (classical salt-wasting (SW), classical simple virilizing (SV) and non classical late onset (LO)) forms of congential adrenal hyperplasia (CAH) due to steroid 21-hydroxylase deficiency, we investigated the urinary excretion of 17-hydroxypregnanolones (17OH-PO(5) and (5), 15-hydroxypregnanolone(15OH-PO), pregnanetriol(PT) and 11-oxo-pregnanetriol (11-O-PT) compared to hydrocortisone metabolities During the 1st month of life newborn infants with CAH-SW excreted from barely detectable to very large amounts of 17OH-PO(5), 15OH-PO and PT, and, in 12 of 14 cases, also 11-O-PT in their urines. From the 1st to the 28th day of life, cortisol metabolites were virtually absent in urines of CAH-SW infants. This was in contrast of 36 healthy newborn infants. We measured the excretion of 17OH-PO(5) in children with CAH of whom 19 patients with CAH-SV had a median 17OH-PO(5) excretion of 1110 g/day (range: 152–5515). In 21patients with CAH-LO, median excretion of 17OH-PO(5) was 294g/day (range: 66–1273). Besides the conventional metabolites of 17-hydroxyprogesterone (17OH-PO(5), PT and 11-O-PT),no 17OH-PO(5) was detected in the urines of 14 patients with precocious pubarche, in 14 patients with virilization of unknown origin and in 94 healthy children of comparable age. The ratio of 17OH-PO(5) to tetrahydrocortisone (THE) discriminated between CAH-SV and CAH-LO from the 1st to the 18th year of age. The determination of urinary 17OH-PO(5) is an excellent diagnostic method in CAH-SV as well as CAH-LO.     

Histochemical and immunohistochemical studies of four proteins (S100-α protein,carbonic anhydrase III,enolase β-subunit,and creatine kinase M-subunit) in rhabdomyosarcoma

Four proteins, the -subunit of S100 protein (S100-), carbonic anhydrase III (CA-III), the -subunit of enolase (EN-), and the M-subunit of creatine kinase (CK-M), are characteristic of skeletal muscle tissue or components. Histochemical studies of human skeletal muscle fibers have shown that S100- and CA-III are localized in type 1 fibers, EN- in type 2 fibers, and CK-M in both fibers. These four proteins were evaluated as markers for rhabdomyosarcoma by enzyme immunoassay and immunohistochemistry. Concentrations of EN- and CK-M were significantly higher in rhabdomyosarcoma than in neuroblastoma or Wilms' tumor. Staining for S100- and CA-III was limited to tumor cells with abundant eosinophilic cytoplasm in most rhabdomyosarcomas. EN- and CK-M staining was also found in several small, round and short, spindle-shaped tumor cells. S100-, CA-III, EN-, and CK-M were demonstrated immunohistochemically in 4 (27%), 7 (47%), 14 (93%), and 12 (80%) of 15 rhabdomyosarcomas, respectively. Our results indicate that EN- is the most useful marker among the four proteins for diagnosing rhabdomyosarcoma.     

15β-Hydroxylated steroids may be diagnostically misleading in confirming congenital adrenal hyperplasia suspected by a newborn screening programme

In a Swiss screening programme for detection of congenital adrenal hyperplasia (CAH), 27 of over 120,000 newborns examined from 1992 to 1994 were further studied because of persistingly high 17 hydroxyprogesterone (17OHP). Out of 27, 11 were later confirmed to have CAH by specific gas chromatography of urinary steroids and ACTH test at age 3–4 months. Of 27, 11 were born at term (7 confirmed 21-hydroxylase deficiency, one 11-hydroxylase deficiency). Out of 27, 16 were preterm newborns. Of them, only 2 were confirmed to have CAH (one 21-, one 11-hydroxylase deficiency). In 3 cases with high 17OHP, but later not confirmed CAH, what appeared to be a pregnanetriolone peak in the gas chromatograms was shown to be 3, 15, 17-pregnenetriol. This compound may be misleading in confirming the diagnosis of CAH. 15-Hydroxylated compounds occur in fetuses, neonates, and amniotic fluid. Since human tissues do not have l5-hydroxylating capacity, their origin is unclear. However, since some bacteria (Bacillus megatherium) and mycelial fungi (fusaria) are known to hydroxylate steroids in position 15, it is likely that this compound is formed by micro-organisms in the enterohepatic circulation of newborns or their mothers.Presented in part as an invited lecture at the symposium on congenital adrenal hyperplasia in honour of Claude Migeon, Baltimore MD, June 11.–13., 1995, and at the 34th Annual Meeting of the European Society for Paediatric Endocrinology, Edinburgh UK, June 25–28, 1995     

β-Adrenoceptor density and resolution of high and low affinity state on B- and T-cells in asthmatic and non-asthmatic children

-adrenoceptor binding in lymphocytes of asthmatic and non-asthmatic children and healthy adult volunteers was investigated with the radioligand 125-iodocyanopindolol (ICYP). Binding studies were performed with 4 to 5 different concentrations of ICYP. Receptor density and affinity were calculated by Scatchard plots. Resolution of -adrenoceptors into those of high and low affinity state was obtained from inhibition curves with salbutamol using Hofstee plots. Receptor density in B-cell enriched fractions was two to three-fold higher than in T-cells for all patients and volunteers studied (P less than 0.025). No difference in -adrenoceptor density on B and T-cells occurred neither in age-matched asthmatic and non-asthmatic children nor in adult volunteers. The affinity of -adrenoceptors did not differ for B and T-cells nor for the patients or volunteers studied. However, when two distinct binding states for -adrenoceptor agonists were obtained using salbutamol displacement curves it appeared that -adrenoceptors on T-cells were at a higher affinity state compared to those on B-cells in asthmatic and non-asthmatic children, as well as in adults. Since the ability of an agonist to activate adenylate cyclase correlates closely with the amount of high affinity receptor state formed in the presence of the agonist, increased intrinsic activity of the -adrenoceptor agonist on T-cells may be postulated. In conclusion, age-related control groups and determination of the B/T ratio are neccessary for interpretation of -adrenoceptor changes in bronchial asthma.Abbreviations ICYP 125-Iodocyanopindolol - BS/B binding sites per B-cell - BS/T binding site per T-cell - KD dissociation constant for the antagonist ICYP - KDL dissociation constant for the low affinity state of the -adrenoceptor for the agonist salbutamol - KDH dissociation constant for the high affinity state of the -adrenoceptor for the agonist salbutamol - H agonist hormones - R -adrenoceptors - N regulatory protein - GTP guanine triphosphate - GDP guanine diphosphate Supported by a grant from the Secretary of Science and Research NRWDedicated to Prof. Dr. G. A. von Harnack on the occasion of this 70th birthdayData were presented at the Paediatric Research Congress, Göttingen, February, 1987     

Die β-Aktivität im EEG des Kindes

Zusammenfassung -Wellen stellen im EEG des Kindes eine labile Aktivitätsform dar. Sie können sowohl spontan erscheinen, als auch durch Reize verschiedener Qualität provoziert werden. Für eine exakte Analyse eignen sich nur die spontanen -Wellen des EEG im Wach-und Schlafzustand, deren formale und topographische Merkmale in den einzelnen Altersstufen aufgezeigt werden. Während die Lokalisation der -Wellen mit geringen Ausnahmen bei allen Kindern über den vorderen Hirnregionen liegt, variieren Frequenz und Amplitude innerhalb bestimmter Grenzbereiche. Die Normalkriterien der spontanen -Aktivität beim Kinde bilden die Grundlage für die Erkennung anormaler -Wellen, wie sie bei cerebralen Erkrankungen auftreten können.     

Age-dependency of alpha- and beta-adrenoceptors on thrombocytes and lymphocytes of asthmatic and nonasthmatic children

Among the possible mechanisms which may cause wheezing or asthmatic episodes a genetically determined -adrenoceptor blockade and a hyperresponsiveness of -andrenoceptors has been postulated. Evidence to support this hypothesis stems from an increased bronchial sensitivity to -blockers, a reduced formation of cyclic AMP in response to -adrenergic stimulation and enhanced -adrenergic responses in asthmatic subjects. The recent development of techniques for measuring the specific, high-affinity binding of radiolabeled -and -adrenergic antagonists made it possible to study - and -adrenoceptors in vitro. Based upon the assumption that a change in the number and/or affinity of adrenergic receptors might be a general phenomenon, we have performed - and -receptor binding studies on lymphocytes and platelets from wheezing infants and asthmatic children as well as of infants, children, and adults not suffering from these diseases.Using ¹²⁵[I]-cyanopindolol (ICYP) and ³[H]-yohimbine (HYOH) as highly specific ligands for - and -adrenoceptors, the following results were obtained: (1) Lymphocytes and platelets from control subjects and asthamatics bound similar amounts of ICYP and HYOH and thus showed no differences either in the number or the affinity of - and -adrenoceptors. Lymphocytes and platelets of wheezing and nonwheezing infants also bound the same amounts of the radioligands. (2) In asthmatic children receiving 4×2 puffs salbutamol -adrenoceptor were down-regulated and this may mimic -adrenoceptor blockade. (3) When subjects were divided into four categories according to age (0–5, 5–10, 10–20 years, adults) the number of -adrenoceptor binding sites showed an age-dependent increase. The number and affinity of -adreneceptor binding sites on platelets was neither influenced by age nor disease.It is concluded that the - and -adrenoceptors of wheezing infants and asthmatic children at least on blood cells are normal. However the -adrenoceptors show an age-dependent maturation process, which may account for an unresponsiveness to -adrenoceptor agonists in wheezing infants.Supported by a grant from the Ministerium für Wissenschaft und Forschung, NRWPresented at the 19th Workshop for Pediatric Research, University of Göttingen, March 10–11, 1983     

Fat-derived fuels during a 24-hour fast in children

We examined the availability of fat-derived fuels in 23 normal children aged 1.9 to 16.7 years who fasted for 24 h. we found a rapid and progressive rise in the blood concentrations of free fatty acids (FFA) and ketones. There was a highly significant negative correlation between the concentrations of -hydroxybutyrate (OHB) and glucose and also between OHB and age.With time, the ratio of OHB to acetoacetate (AcAc) progressively increased.We briefly review the vital role of ketones in the adaptation to fasting and point out that qualitative tests of ketones can be misleading. Our results indicate that quantitative determinations are essential in the evaluation of suspected disorders of fuel metabolism and that the results must be interpreted according to the age of the child, the duration of fasting, and the concomitant concentrations of glucose.Presented in part at the annual meeting of the American Pediatric Society and Society for Pediatric Research, San Francisco, April 1981     

Fetal bile acids in congenital biliary atresia —production in the liver and clinical significance

The 1-hydroxy bile acids have been said to be fetal bile acids. These bile acids were evaluated in eight patients with congenital biliary atresia (CBA) using gas chromatography-mass spectrometry. At the time of operation 1,3,7,12-tetrahydroxy-5-cholan-24-oic acid (CA-1-ol) and 1,3,7-trihydroxy-5-cholan-24-oic acid (CDCA-1-ol) were 0.46 ± 34 g/ml and 0.72 ± 0.45 g/ml, respectively, which was significantly higher than in the control group. The percentage CA-1-ol of total bile acids showed a tendency to decrease as age advanced. The grade of hepatic fibrosis ranged from F₂ to F₃ and the values and percentages of CA-1-ol and CDCA-1-ol were relatively higher in F₂ than F₃ patients. The percentage of total bile acids gradually increased in patients without sufficient bile flow but fell sharply after Kasai's procedure in the patients with sufficient bile flow. It appears that fetal bile acids are produced in the livers of CBA patients in the same way as in fetal liver, and that production continues in patients without good bile secretion even after Kasai's procedure. These results suggest that these hydroxylases are reactivated in CBA patients.     

Tumour necrosis factor in neonatal listeriosis: a case report

A newborn with fatal neonatal listeriosis developed septic shock, neutropenia, thrombocytopenia and profound hypoxaemia due to severe pulmonary hypertension. Tumour necrosis factor , interleukin-1- and interferon- serum concentrations were markedly elevated, suggesting the participation of these cytokines in the aetiopathogenesis of shock induced by Listeria monocytogenes in the neonate.Abbreviations IFN- interferon- - IFN- interferon- - IL-1 interleukin-1 - MPA monocytosis producing agent - TNF- tumour necrosis factor      

A physiological mode of puberty induction in hypogonadal girls by low dose transdermal 17β-oestradiol

Transdermal 17-oestradiol administration (17-E₂), used mainly in menopausal women, allows a continuous 17-E₂ delivery through the skin into the systemic circulation, avoiding intestinal and hepatic passage. In order to explore whether transdermal 17-E₂ could be used for the induction of puberty, 17-E₂ patches with low dose delivery were administered in nine prepubertal girls with Turner syndrome (bone age >10.5 years) for a mean period of 2.2 years. Treatment schedule: 5 g/day for 6–9 months, 10 g/day for 6–9 months, 25 g/day for long-term substitution; addition of cyclic gestagen p.o. after 18–24 months. Breast development started within 3 months of therapy and menstruation occurred after 2 years. Growth rate increased from 3.2 to 5.0 cm/year during the 1st year of therapy, height prediction did not change. Serum oestradiol (E₂) and urinary E₂ conjugates increased proportionally with 17-E₂ doses, serum oestrone (E₁) rose much less. The possibility to imitate time course, clinical events and hormonal changes of normal puberty, the absence of adverse drug reactions and the excellent acceptance and easy mode of application suggest that transdermal 17-E₂ is optimally suited for hormonal substitution in girls with hypogonadism.Presented in part at the Annual Meeting of the European Society for Paediatric Endocrinology and the LWSPE, Jerusalem November 1989     

Peroxisomal β-oxidation defect with detectable peroxisomes: A case with neonatal onset and progressive course

A progressive demyelinating cerebral disorder is described in a normally-appearing female infant with neonatal seizures, progressive psychomotor deterioration, deafness, retinopathy, peripheral neuropathy and loss of myelin observed on magnetic resonance imaging (MRI) scanning. MRI also showed the absence of macroscopic neocortical dysplasia which is usually found in Zellweger syndrome (ZS). Adrenal cortical function was normal. The patient died at the age of 37 months. Extensive biochemical investigations of peroxisomal functions in the patient revealed an impairment of peroxisomal -oxidation resulting in elevated levels of very long (>C₂₂) chain fatty acids in plasma and fibroblasts. Moreover, elevated plasma levels of intermediates of bile acid biosynthesis such as tri- and dihydroxycholestanoic acid were found. Other peroxisomal functions were normal. Immunoblotting of the peroxisomal -oxidation enzyme proteins in liver from the patient revealed normal responses with antisera against acyl-CoA oxidase, bifunctional protein and thiolase respectively. From these data we conclude that the patient had a deficiency of a single peroxisomal -oxidation enzyme at the level of either the bifunctional protein or peroxisomal thiolase with retained immunoreactivity against these enzymes.     

Variable outcome of experimental interferon-γ therapy of disseminated Bacillus Calmette-Guerin infection in two unrelated interleukin-12Rβ1-deficient Slovakian children

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) is an attenuated live vaccine that may cause life-threatening clinical disease in children with impaired immunity. In particular, patients with any of the nine known inherited disorders of the interleukin-12/23 interferon- (IL-12/23-IFN) axis are highly vulnerable to BCG. We describe two unrelated young Slovakian children suffering from disseminated BCG infection which developed shortly after routine BCG vaccination after birth. During treatment with selected anti-BCG antibiotics, resistance against several of these drugs developed. In both children, interleukin-12/23 receptor 1 (IL-12/23R1) deficiency was diagnosed. Thus, in addition to chemotherapy, immunomodulatory treatment with recombinant IFN- was performed as the pathogenesis of BCG disease in IL-12R1 deficiency involves impaired IL-12- and IL-23-dependent IFN- production by lymphocytes. One child responded to treatment and is presently doing well whereas the second patient died. Conclusion:The marked variability of outcome of disseminated Bacillus Calmette-Guerin disease in interleukin-12/23 receptor 1-deficient children sharing the same ethnic origin and exposed to a similar environment as presented in these case reports has to be taken into consideration for diagnosis and treatment of infections due to this genetic defect.T. Ulrichs and C. Fieschi, S. H. E. Kaufmann and J-L. Casanova contributed equally to this work