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.     

The value of the routine chest roentgenogram in the cardiological evaluation of infants and children. A prospective study

The value of the routine chest roentgenogram was studied in 284 patients, newly admitted to our paediatric outpatient department. Emergency patients were excluded from the study. In 141 cases the initial diagnosis after history, physical examination and ECG was no heart disease, while in 143 cases it was heart disease. After a follow up of up to 4 years, 170 children appeared to have no heart disease and 114 definite heart disease. In 7.7% of cases the chest roentgenogram made at the first visit to the outpatient department led to a change in policy, whereas in only 3.8% was the chest roentgenogram in someway helpful in establishing the correct diagnosis. Amongst those children with initial diagnosis of innocent murmur, the chest roentgenogram led to a diagnosis of heart disease in only 2.8% of cases. It is concluded that for the differentiation heart disease or no heart disease, a chest X-ray film is not indicated. In children with heart disease the chest X-ray film is also of little value, and is mostly to be used only for documentation.Partly presented at the Jahrestagung der deutschen Gesellschaft für pädiatrische Kardiologie, Düsseldorf, 1–2 Oktober 1984     

“Inborn errors of metabolism” and “chemical individuality” two ideas of Sir Archibald Garrod briefly revisited 50 years after his death

Two ideas of Sir A. Garrod, chemical individuality (1902) and inborn errors of metabolism (1908) have proved fundamental for the development of medical knowledge. The latter idea was more fortunate than the former which, however has been extremely heuristic. On the other hand the two ideas are not entirely independent of each other: in fact, a third Garrodian concept, inborn factors in disease, represents a significant link between them. Inborn errors of metabolism revived the laws of genetics and opened the way to interpretation of the molecular diseases with all their inherent practical modern implications (neonatal screening, prenatal diagnosis, and in perspective, genetic engineering). Chemical individuality still constitutes a valid premise for knowledge of biological individuality (in other words, the biological ego) fundamentally programmed for conservation of self and for continuous discrimination of self versus non-self.     

Relationship between café-au-lait spots as the only symptom and peripheral neurofibromatosis (NF1): A follow-up study

We re-examined 21 children with the possible diagnosis of peripheral neurofibromatosis (NF1) based on the presence of cafè-au-lait (CAL) spots as the single clinical finding. We evaluated whether typical or atypical appearance of the spots was important for the final diagnosis and whether the co-existence of other nonspecific signs (e.g. pectus excavatum) were of any significance for the final diagnosis. In 8/14 (57.1%) cases with typical CAL spots, the diagnosis of NF1 was finally established on the basis of other criteria. For the other 6 patients the diagnosis is not yet definitive but highly probable on the basis of the presence of macrocephaly, pectus excavatum and/or MRI findings. Only one patient among five with atypical CAL spots possibly has NF1.     

Biofeedback in spina bifida

The use of anorectal manometry as a biofeedback technique in the treatment of constipation and fecal incontinence in patients with spina bifida is described. The technique was applied in ten incontinent spina bifida patients aged 3 to 16 years. To evaluate our results we used the concept of controlled incontinence, i.e., voluntary defecation at set times, with the patient remaining clean the rest of the time as a base. A total of 80% satisfactory results was obtained. Offprint requests to: J. M. Gil-Vernet     

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     

Silent carrier β-thalassaemia due to a severe β-globin mutation interacting with other genetic elements

Beta-thalassaemia is caused by the presence of two mutated -globin genes, one inherited from each parent. We describe two families in which the diagnosis of -thalassaemia intermedia was delayed because one of the parents, an obligatory heterozygote, had normal haematological parameters (silent carrier -thalassaemia). DNA analysis revealed that these silent carriers were heterozygous for a point mutation in the polyadenylation signal (AATAAA-AATAAG). This defect is known to cause a moderately severe -thalassaemia phenotype. In one case, concurrent deletional -thalassaemia was found in the silent carrier, which may have contributed to the mild phenotype. The increasing availability of DNA analysis should allow prompt diagnosis of such cases. Silent carrier -thalassaemia presents a diagnostic challenge to the clinician who evaluates children with anaemia.     

IgG,IgA and IgE gliadin antibody determinations as screening test for untreated coeliac disease in children,a multicentre study

The diagnostic value of gliadin IgG, IgA and IgE antibody (AB) determinations using the fluorescent immunosorbent test was examined in 586 children with malabsorptive disorders and/or failure to thrive. All patients underwent jejunal biopsy and were on a gluten-containing diet. IgG AB were found in all patients (331/331) with untreated coeliac disease (CD) in our study, but IgA AB in only 295/331 (89%). Therefore a screening test based only on IgA AB determinations is not recommended. By contrast, 203 (80%) of 255 children with other malabsorptive disorders had no gliadin AB, 43 (16.5%) had only IgG AB and only 9 (3.5%) had IgG and IgA AB. IgE AB proved to be of no additional value as a diagnostic tool because they were found in a quarter of the children without CD. Statistical evaluation of combined IgG and IgA AB determination showed at least 96% sensitivity and a specificity of 97%. The subjective (Bayesian) probability that an actual patient with a given AB test result has CD, is considered: a patient very probably has CD in the case of positive IgG and IgA AB, and no CD in the case of a negative AB result. In the case of negative IgA AB but positive IgG AB the physician's judgement (prior probability) influences the (posterior) probability of CD for an actual patient. In contrast to IgG AB, IgA AB decline rapidly after the introduction of a gluten-free diet and may be used for diet control after diagnosis. Antibodies against cow's milk proteins, though present in 72% of the 331 patients with CD, are of no therapeutic significance in CD and are of no value for its diagnosis.Abbreviations AB antibodies - CD coeliac disease - FIST fluorescent immunosorbent test     

The contribution of protein catabolism to metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria

Leucine and protein metabolism were studied using stable isotope techniques in 6-year-old twins with 3-hydroxy-3-methylglutaric aciduria during acute metabolic decompensation. The decompensation was preceded by prolonged fasting in twin 1 and by an upper respiratory infection in twin 2. Twin 2 was also studied when well (control study). During infection, leucine oxidation (36 mol/kg per hour), protein catabolism (6.0 g/kg per day) and urinary excretion of major leucine metabolites (104 mol/kg per hour) were all increased compared with the control study (16 mol/kg per hour, 4.7 g/kg per day and 28 mol/kg per hour respectively). During fasting, leucine oxidation (18 mol/kg per hour) was unchanged and protein catabolism (4.1 g/kg per day) was decreased despite substantially increased urinary metabolite excretion (87 mol/kg per hour) compared with the control study. These results indicate that protein mobilisation and leucine oxidation played important roles in metabolic decompensation during infection but not during fasting. It is likely that the increased metabolite excretion during fasting arose primarily from fatty acid catabolism, indicating the importance of this substrate in metabolic decompensation in 3-hydroxy-3-methylglutaric aciduria.     

Undescended testes: early versus late maldescent

A review of 468 orchidopexies was undertaken to ascertain the importance of a complete hernial sac extending to or beyond the testis. A hernial sac was present in 84% (171/202) of testes in patients under 5 years of age, in contrast to 23% (61/266) in patients over 5 years. It seems reasonable to presume that the failure of the hernial sac to close is secondary to failure of normal descent, which in turn is due to antenatal factors and may be classified as early maldescent. In the older age group maldescent is due to failure of the last stage of descent, which should occur in the 5- to 10-year prepubertal age period (late maldescent, or the ascending testis). The cause of late maldescent is not due to a short processus, as this increases in length with age (approximately 0.5 cm/year), unless the persistence of the processus itself is the cause. A classification of early or late maldescent is suggested.     

Hypertension in a neonate with 11 β-hydroxylase deficiency

A female newborn infant with ambiguous genitalia was found to have hypertension (121/82 mm Hg) immediately after birth. The plasma testosterone (T) (0.73 nmol/l), 4-androstenedione (4-A) (5.9 nmol/l), dehydroepiandrosterone (DHEA) (8.9 nmol/l), as well as 17 OH-hydroxyprogesterone (17 OHP) (152 nmol/l) were elevated. The diagnosis of 11-hydroxylase deficiency was finally established on the basis of elevated plasma eleven-deoxycortisol (compound S) (>0.6 mol/l) and confirmed by the normalisation of the blood pressure during hydrocortisone therapy. Our case is probably the youngest patient with 11-hydroxylase deficiency in whom the hypertension was found at birth.Abbreviations T testosterone - OHCS 11 hydroxycorticosteroids - DOC deoxycorticosterone - THDOC tetrahydrodeoxycorticosterone - THS tetrahydro S - 17 OHP 17 OH-hydroxyprogesterone - DHEA dihydroepiandrosterone - DO 11-deoxycorticosterone - ₄A androstenedione     

High resolution CT of the lungs in acute disseminated tuberculosis and a pediatric radiology perspective of the term “miliary”

High resolution CT (HRCT) of the lungs in six children with acute disseminated tuberculosis was evaluated. There was a wide variation in the HRCT appearances. This covered differences in size, distribution and concentration of nodular opacities. Coalescence of nodules and the presence of intestitial thickening was variable. The recognition of acute disseminated tuberculosis is important for diagnosis and has prognostic implications. The use of the term acute disseminated tuberculosis rather than miliary tuberculosis is advocated.     

Densitometric measurement of renal echogenicity in infants and naked eye evaluation: A comparison

The sonograms of 115 infants with normal renal function ranging in age from 1 to 120 days used to determine renal parenchymal echogenicity by densitometry. The measured values were contrasted with the evaluations of 4 independent examiners who rated renal echogenicity as less than, equal to or greater than that of the liver. The results revealed that naked eye evaluation does not permit a clear distincition between the categories of echogenicity and also that the assessments of the individual examiners differed considerably. Contrary to the previously held view the present findings indicate that the initially increased renal parenchymal echogenicity in neonates has developed into the normal hypoechoic condition after 1 month. One should take these findings into account when evaluating renal sonograms of infants, especially if no densitometric data are available.     

Haematological improvement by long-term administration of recombinant human granulocyte-colony stimulating factor and recombinant human erythropoietin in a patient with severe aplastic anaemia

A 6-year-old girl with post-hepatitic severe aplastic anaemia was referred to our hospital. Haematological examination showed a haemoglobin level of 5.2 g/dl, platelet count of 8,000/l, and white blood cell count of 130/l with 17% neutrophils. She was treated with recombinant human granulocytecolony stimulating factor (15 g/kg/day i.v.) and cyclosporin A (6 mg/kg/day p.o.). The absolute neutrophil count gradually increased, but Hb and platelets were not improved. The intravenous administration of recombinant human erythropoietin (100 U/kg three times a week) was started, and the reticulocyte count reached 20000/l on day 12. The platelets increased to 81000/l after 16 months of combined administration of recombinant human granulocyte-colony stimulating factor, recombinant human erythropoietin and cyclosporin A. After 20 months of combined administration, the haematological results were: Hb, 13.1 g/dl; platelets 80000/l: WBC, 9500/l with 40% neutrophils. After recombinant human granulocyte-colony stimulating factor treatment, the myeloid elements of the bone marrow and the number of granulocyte-macrophage colony forming units increased. Bone marrow erythropoiesis and erythroid colonies also increased after recombinant human erythropoietin administration. The clinical course suggested a beneficial effect of haemopoietic growth factors and cyclosporin A in post-hepatitic aplastic anaemia.     

Beobachtungen bei Cystinspeicherkrankheit

Schlußfolgerungen und Zusammenfassung Es wird von einem 11 Monate alten Kind berichtet, bei welchem eine Erkrankung der Harnwege mit Zwergwuchs, Rachitis, Aminoacidurie und Kristallablagerungen in Knochenmark und Conjunctiva nachgewiesen wurde. Erblichkeit, Blutsverwandtschaft der Eltern zeigen die Wirkung des Cystin-Gen in der Familie des Kindes, in welcher eine Cystin-Diathese bereits zu unerkannten Störungen führte, bevor sich bei der Patientin nach dem Auftreten einer entzündlichen Erkrankung der Harnwege in früher Kindheit die voll ausgebildete Cystinkrankheit manifistierte. Im Urin wurden Aminosäuren vermehrt ausgeschieden, ferner gebundenes Cystin, freies Cystin jedoch nicht. Im Blut hingegen war gebundenes Cystin zweifelsfrei auf das Doppelte vermehrt, während eine Vermehrung von freiem Cystin nicht nachweisbar war. Von den freien Aminosäuren wurden diejenigen im Serum vermehrt angetrffen, die auch im Urin vermehrt ausgeschieden wurden. Mithin würde unser Fall nach Fanconis hypothetischer Einteilung die metabolische Form der Aminoacidurie repräsentieren. Darüber hinaus fordert er zu der Deutung auf, daß überhaupt die metabolische Komponente bei der Entstehung der Krankheit vor der renalen rangiert, womit wir den Anschauungen von Bickel, Freudenberg, Linneweh und Ullrich beipflichten. Die abnorme Anhäufung von Cystin in den Geweben und im Blut steht im Vordergrund. In den Geweben wurde außer Cystin noch ein anderer, kristallographisch unterscheidbarer Stoff nachgewiesen.     

Further evidence for infectious origin of isolated transient hyperphosphatasaemia

Marked transient increases in serum alkaline phosphatase activity were found in three siblings with upper respiratory tract infections. This supports observations suggesting an infectious origin of the condition termed transient hyperphosphatasaemia of infancy and early childhood.Abbreviations AP alkaline phosphatase - ITH isolated transient hyperphosphatasaemia     

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.     

Zur konstitutionellen Dysotosis enchondralis,insbesondere zur Pfaundler-Hurlerschen und Morquioschen Krankheit

Zusammenfassung Eingehende Stellungnahme zur konstitutionellen Dysostosis enchondralis. Anerkennung als Dachbegriff und Befürwortung desselben. Umgrenzung seines derzeitigen Inhalts, als welcher die Dysostosistypen Ribbing und Morquio, die Dysostosis multiplex v. Pfaundler-Hurler, die Cystinkrankheit sowie bisher mehr-minder vereinzelt dastehende Beobachtungen zu nennen sind. Stellungnahme zu manchen der letzteren und zur multiplen Epiphysenstörung. Ablehnung röntgenoskopischer Unterscheidungsmöglichkeit zwischen Formen mit epiphysär, meta- und epiphysär bzw. metaphysär lokalisierten Veränderungen als klinisches Ordnungsprinzip.. —Ins Einzelne gehende Erörterung der Abgrenzung zwischen Dysostosis Morquio und dem lipoidfernen Symptomenkomplex der klassischen sowie der Spätform der Pfaundler-Hurlerschen Krankheit. Skeletröntgenoskopische Abtrennung zwischen Späthurler und Morquio erscheint vorerst unmöglich. Tabellarische Zusammenstellung der Unterschiede zwischen den genannten Affektionen. — Abschließend kurze Ausführungen zur Pleonosteosis familiaris Léri.     

Fermoral hypoplasia-unusual facies syndrome from another viewpoint

A female infant with the femoral hypoplasia-unusual facies syndrome is presented. Most of the findings observed in this child have also been described in the caudal regression syndrome. The similarity and probable identity between these two syndromes is discussed on the basis of our patient and others from the literature.This work partially supported by the Indiana University Human Genetics Center, PHS GM 21054 and the Oral-Facial Genetics Training Grant DE 00007-2     

β2-mikroglobulin bei gesunden und nierenkranken Kindern

Zusammenfassung ₂-Mikroglobulin ist ein Plasmaprotein niedrigen Molekulargewichts (11800), das in geringen Mengen auch im Harn und Liquor vorkommt. Seine Serumkonzentration liegt bei gesunden Kindern bei 0,12±0,04 mg/100 ml, seine renale Ausscheidung bei 0,07±0,05 mg/24 Std. Bei glomerulärer Nephropathie sind die Serumspiegel bei eingeschränkter GFR erhöht, während bei tubulärer Nephropathie die Ausscheidung im Harn erheblich gesteigert ist. Es besteht eine enge Korrelation zwischen ₂-Mikroglobulin und der GFR.

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₂-microglobulin in healthy children and in children with renal diseases

₂ microglobulin is a plasma protein of low molecular weight (11800), which also appears in urine in small quantities and cerebrospinal fluid. Its serum concentration in healthy children is 0.12±0.04 mg/100 ml, its renal excretion is 0.07±0.05 mg/24 hrs. In glomerular nephropathy serum levels are augmented with diminished GFR, while in tubular nephropathy excretion in the urine is raised considerably. There is a close correlation between serum ₂ microglobulin and GFR.