P. van Munster

A NEW CHROMOSOMAL INSTABILITY DISORDER: THE NIJMEGEN BREAKAGE SYNDROME

ABSTRACT. Weemaes, C. M. R., Hustinx, T. W. J., Scheres, J. M. J. C, van Minister, P. J. J., Bakkeren, J. A. J. M. and Taalman, R. D. F. M. (Departments of Paediatrics and Human Genetics, University of Nijmegen, Nijmegen, The Netherlands.) Acta Paediatr Scand, 70:557,.–A 10‐year‐old boy with microcephaly, stunted growth, mental retardation, cafe‐au‐lait spots and immunodeficiency is described. An older brother of the patient had the same clinical symptoms and a more severe immunodeficiency. Cytogenetic studies in the proband revealed a typical form of chromosome instability with multiple rearrangements of chromosomes 7 and 14. Such abnormalities were also present, though in very low frequencies, in the father and three of the phenotypically normal sibs. The similarity of the symptoms in the two sibs, the close consanguinity of their parents and the results of the cytogenetic studies in the family favour the hypothesis that the disorder is an inherited one. The clinical features and the chromosome aberrations as present in the proband are usually found in chromosomal breakage syndromes, but it was possible to exclude each of the classical chromosomal breakage syndromes on clinical and/or cytogenetic grounds.

Levels of renin, angiotensin I and II, angiotensin-converting enzyme and aldosterone in infancy and childhood

Basal plasma renin activity (PRA), angiotensin I and II (AI, AII), angiotensin-converting enzyme (ACE) activity and plasma aldosterone (PA) and sodium and potassium concentration were simultaneously measured in 55 healthy recumbent children aged between 1 week and 13 years. A significant (P<0.001) age-related decrease for PRA (r=-0.73), AI (r=-0.72), AII (r=-0.51) and PA (r=-0.71) was observed but not for ACE (r=0.26, P=0.06). After correction for age the correlation between PRA or PA and AI or AII was still significant (P<0.005). The strong correlation between AI and AII in the group as a whole (r=0.82, P<0.001) and also in separate age groups, and an AI to AII ratio which was not different between the various age groups suggest that ACE activity in this age range is not rate-limiting for AII generation.

Clinical manifestations in selective IgA deficiency in childhood. A follow-up report.

ABSTRACT. Clinical manifestations in 40 children with selective IgA deficiency were studied during a follow‐up period of 2‐10 years. The patients were divided into two groups: group I consisted of 25 children with “sporadic” IgA deficiency and group II of 15 children with “familial” IgA deficiency. Respiratory tract infections including otitis media were frequent in both groups. Concomitant IgG,‐IgG, deficiency was found in two patients in group I. Longitudinal serum IgG levels were elevated significantly in both groups. Atopic complaints were observed in 10 children of the “sporadic” group, but only in two of the “familial” group. However, elevated serum IgE levels were more often found in group II. Two children of group I were mentally retarded and chromosomal examination showed abnormalities in both. Anti‐IgA antibodies were detected in one child in group I and three children in group II. These three patients had an IgA deficient mother with class‐specific anti‐IgA antibodies. Concomitant IgG4‐IgE deficiency was found in all four.

Low-Renin, Low-Aldosterone Hypertension and Abnormal Cortisol Metabolism in a 19-Month-Old Child

A 19-month-old boy presented with failure to thrive and polydipsia. Low-renin hypertension was diagnosed by the presence of hypertension, hypokalaemic alkalosis, suppressed plasma renin activity and low plasma aldosterone. Plasma levels and urinary excretion of other mineralocorticoids and glucocorticosteroids were low or normal. Urinary tetrahydrocortisol (THF) was increased relative to tetrahydrocortisone (THE) and also the plasma cortisol to cortisone ratio was elevated. These findings are suggestive of a decreased activity of cortisol-11 beta-hydroxysteroid dehydrogenase. Hypertension and hypokalaemia were not influenced by spironolactone and dexamethasone. Triamterene normalised serum potassium, but addition of furosemide was required for lowering blood pressure. With this treatment catch-up growth was observed.

Recovery of immune function after cessation of maintenance therapy in acute lymphoblastic leukemia (ALL) of childhood

In previously healthy children, serum immunoglobulin levels at diagnosis of acute lymphoblastic leukemia (ALL) were entirely in the normal range. After antileukemic therapy had been given for 26–27 months, serum immunoglobulin levels were low. In 32 children these parameters could be followed for periods up to 3 years after cessation of therapy, the patients remaining in unmaintained remission.At cessation of therapy serum immunoglobulin levels were at the tenth centile of the normal range or slightly below. IgG promptly returned to normal levels and then remained in the normal range. IgA levels were restored much more slowly. Most striking was the slow and incomplete return of serum IgM to normal levels. Even after a follow-up of 3 years the mean was still subnormal. This was not accompanied by clinical signs of disturbed immunity. Our study points out that in assessing the long-term immunosuppressive effects of anticancer therapy the follow-up period must be sufficiently long.

A turbidimetric immuno assay (TIA) with automated individual blank compensation

A simple and sensitive turbidimtric immunoassay (TIA) has been described. The automated method has been based on the use of the LKB reaction rate analyser, an instrument that is already present in many clinical chemical laboratories. The precipitin reaction is accelerated and enhanced by poly-ethylene glycol 6000 at a concentration of 50 g/l. Sample volume 2--100 micronl. Use of antiserum: 3--15 micronl per test. Sampling rate 30--60 samples per hour. The choice and the usefulness if antisera is discussed. The major advantage of the present method is the individual measurement and compensation for the initial absorbance (340 nm) immediately after the mixing of antigen and antiserum. This enables the determination of very low serum protein concentrations (from 0.005 mg/ml) which is not possible with other methods that require separate blank determinations. The turbidity course is different in antigen and antibody excess. The The chance of misinterpretation is small. The precision of the method is satisfactory. Within-run precision is 1--2% (C.V.) in the IgA/anti-alpha-system. Between-run-precision in the IgM/anti-micron system: 3.9% (C.V.). The day-to-day precision for IgG, IgA and IgM determinations resulting from a 7-month period of quality control was found to be 6.1% and 10.5%, respectively. RID and TIA methods agree very well. IgM determinations in cord serum from 104 newborns revealed a mean value and standard deviation of 14.6 +/- 6.3 I.U./ml (0.13 +/- 0.06 mg/ml).

The renin-angiotensin-aldosterone system in infancy and childhood in basal conditions and after stimulation.

Plasma renin activity (PRA), aldosterone (PA), sodium and potassium concentration were measured in 107 healthy infants and children under basal conditions of normal diet and recumbency. Urinary aldosterone (UAldo), sodium and potassium were also measured (n=51). A significant (P<0.001) age-related decrease in PRA (r=-0.67), PA (r=-0.67), and UAldo (r=-0.56) was observed, with a striking scatter of values especially in infancy. The renin-angiotensin-aldosterone system (RAAS) was also studied after stimulation by standardised sodium restriction during 4 days, followed by acute postural change (n=40). After salt restriction a rise of PRA and UAldo was noted, but a rise in PA could not be demonstrated in children aged 0–6 months. The influence of postural change on the RAAS seems more important in older children. The reported values not only in basal but also in stimulated conditions allow study of the RAAS in diseases such as salt loss and hypertension.

Experience in the netherlands with an external quality control and scoring system for clinical chemistry laboratories

A procedure is described to judge the quality of clinical chemistry hospital laboratories in The Netherlands. In 1974, 45% of the laboratories took part in the national control scheme. A score system of the results, independent of the standard deviation, opens a provisional possibility to strive for (dynamic) reference laboratories. The Youden plots possibly will unveil systematic method-differences. Discrepancies in results seem to be caused as much by methods/instruments applied, as by unknown factors which are under investigation now.

Immune responses in four patients with Bloom syndrome.

Abstract Immunological examinations of four patients with Bloom syndrome, belonging to two families, revealed some disturbances of the immune function. All patients had decreased levels of at least one class of immunoglobulins. The disturbances of the lymphocyte stimulation tests demonstrated a remarkable similarity in the siblings: decreased stimulation in vitro by phytohemagglutinin (PHA) and pokeweed mitogen (PWM), low responses on stimulation by specific antigens, and diminished responder capacity in mixed lymphocyte reaction (MLR) in both patients of family I: normal stimulation in vitro by PHA and PWM, high responses on stimulation by specific antigens, and diminished responder capacity in MLR in both patients of family II. This remarkable difference in expression of the defect between both families could be the expression of a genetic heterogeneity.

A new sensitive method for the determination of serum carnosinase activity using l-carnosine-[i-14C]β-alanyl as substrate

Abstract A new method has been developed for the determination of serum carnosinase activity using l -carnosine-[1- 14 C]β-alanyl as substrate. The serum carnosinase activity was calculated from the ratio decomp./min β-alanine: total decomp./min at the end of the incubation. The K m -value of the serum carnosinase-catalysed hydrolysis of l -carnosine was found to be 7.1 · 10 −5 M. In adults the mean value for serum carnosinase activity amounted to 44.2 ± 14 (S.D.) units/1. In serum of newborns only very low carnosinase activities were found. This sensitive method may be applied to detect patients with serum carnosinase deficiency.