Biomedical subjects
Publications and source records attributed to L Corbeel.
Identical twin-sisters with evidence of a demyelinating disease showed multiple serum glycoprotein abnormalities. The association of a low serum iron level and a normal blood haemoglobin suggested an abnormality of transferrin too. This was confirmed by finding a sialic acid-deficiency of this glycoprotein in serum as well as in cerebrospinal fluid.
A girl, 13 months of age, presented with generalised granulomatous skin, hair and mucosal candidiasis. Her lymphocytes failed to respond in vitro to Candida antigen (CA); the intradermal test with CA was also negative. Serum immunoglobulins, complement components, granulocyte functions (phagocytic and fungicidal), T-cell subsets, mitogenic and allogenic lymphocyte stimulation, natural killer cell activity and immune interferon production were all found to be normal. No circulating immune complexes were detected. Ketoconazole, an antimycotic drug, 5 mg/kg twice daily for 1 month and 2.5 mg/kg twice daily for another month spectacularly cleared all lesions. Afterwards, 4-monthly injections with transfer factor (TF) were given. Intradermal reactivity to CA was observed after the second TF injection. The lymphocyte responsiveness to CA in vitro became strongly positive 3 months after the last TF injection. The level of CA precipitins in serum, which was very high (11 lines) before ketoconazole treatment, decreased to 4 lines. No serum inhibitor of lymphocyte proliferation to CA could be demonstrated in the patient's serum before or after treatment. This specific CA unresponsiveness was not due to an excess of OKT8 + (suppressor) cells; macrophage migration inhibiting factor (MIF) production was normal. The nonresponsiveness might be due to antigenic overload or to suppressor cell induction not demonstrable in the present studies. The child has remained free of lesions during 3 years of follow-up without any further treatment.
Ultrastructurally atypical bronchial cilia are studied and semiquantitatively analysed in 24 children suffering from recurrent respiratory tract infections with or without bronchiectasis. In patients with Kartagener's syndrome normal-looking and shortened dynein arms are present at some axonemal microtubular doublets. This finding suggests that the polymerization or assemblage of dynein molecules on microtubules only is defective but not totally lacking. Bilateral, local and partial absence of dynein arms is demonstrated in some of the patients with acquired unilateral bronchiectases. These patients also reveal anomalies of the "9 + 2" microtubular axonemal pattern. It is suggested that these abnormalities of the tubulin-dynein system are local and acquired defects that may impair bronchial mucociliary clearance. None of the patients with pneumonia and asthma or with cystic fibrosis studied show any anomalies of the dynein arms. However aberrant axonemal microtubular patterns and other ciliopathies such as naked axonemes and megacilia are present at times in these patients. We postulate that these atypical cilia are secondary acquired abnormalities. Only some patients with bacterial or viral pneumonia demonstrate a partial lack of dynein arms in bronchial cilia. Other ciliopathies such as megacilia, naked and intracytoplasmic axonemes and apical blebs are more frequent and more common in these patients. We suppose they manifest a secondary and rather aspecific pathogenic influence upon the bronchial ciliary substructure.
Cerebrospinal fluid aminoacid analysis in a girl with severe psychomotor retardation, hypotonia, hyperreflexia and growth acceleration showed highly increased levels of free gamma-aminobutyric acid (4.8 mumol/l; range in twenty controls 0.04-0.12, median 0.08), homocarnosine, a dipeptide of gamma-aminobutyric acid and histidine (23.4 mumol/l; control range 4.0-8.7, median 7.6) and of beta-alanine, an alternative substrate for gamma-aminobutyric acid-transaminase (0.48 mumol/l; control range 0.02-0.06, median 0.05). Liver gamma-aminobutyric acid-transaminase activity was deficient (0.07 mumol/mg protein h; range in ten controls 0.31-0.69, median 0.38). Fasting plasma growth hormone levels were increased (7.9-38.4 ng/ml; nl less than 5). Brain evoked responses were suggestive of leukodystrophy. A brother of this patient, showing a similar clinical picture, had died at one year. Postmortem examination of his brain showed leukodystrophy of the type seen in amino acidopathies such as phenylketonuria. This appears to be the first report of gamma-aminobutyric acid-transaminase deficiency.
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Anomalies of the bronchial cilia were studied in 5 children with recurrent pulmonary infections. Case 1 had Kartagener's syndrome and an absence of the inner and outer dynein arms in most cilia, although a few shortened and even some normal arms could be seen. Cases 2 and 3 had unilateral bronchiectasis without family history of Kartagener's syndrome. Serial studies of the bronchial epithelium at times showed a bilateral lack of the inner dynein arms and a partial lack of outer arms. These abnormalities persisted in these 2 children after they had recovered from the acute pulmonary infection but disappeared after 6-8 months of antibiotic treatment. Cases 4 and 5 had recurrent pulmonary infections without bronchiectasis and many shortened outer dynein arms could be seen, but these anomalies disappeared after recovery. In all 5 children such architectural ciliary anomalies were present as megacilia, fused cilia, naked cilia, and completely disorganised axonemas. These architectural defects were particularly numerous in the children without bronchiectasis. Our observations suggest that anomalies of the bronchial ciliary microtubular system may not only be congenital but may also be acquired; this might well help to explain some cases of repeated respiratory tract infection and bronchiectasis.
A girl presented with an important growth retardation, hepatomegaly, fasting hypoglycemia, lactic acidosis, increased serum cholesterol, triglycerides and uric acid, and increased liver glycogen (7.5%). There was no rise in blood glucose after IV galactose or fructose, but glucagon gave a delayed response. Type Ib glycogen storage disease was suggested by the low normal activity of glucose-6-phosphatase (G-6-Pase) which reached 1.8 units/g (normal, 2 to 10 units/g) and the normal activity of other glycogenolytic enzymes, measured in homogenates prepared in H2O (mean +/- S.E. in control subjects: 59% +/- 7; in type Ia GSD: 92% +/- 3). The activity of G-6-Pase measured as described above increased to 3.8 units/g of liver 1 year after PCS and 7.85 units/g of liver after 3 years. At that time, a simultaneous assay of the enzyme in a fresh, previously not frozen liver biopsy, homogenized in 0.25 M sucrose, revealed only about 29% of the activity of the same sample prepared in H2O (mean +/- S.E. in three controls: 95.8% +/- 8.9.
A case of dyskeratosis congenita is reported. This rare hereditary disease usually has the following progression: ectodermal dystrophy (reticular skin pigmentation, nail dystrophy, leukokeratosis of mucosal membranes), appearing in the first decade, followed in about 50% of these patients by a hematopoietic disorder resembling Fanconi's anemia, usually developing in the second or third decade. Carcinomas may occur in leukokeratotic areas in the third, fourth, or fifth decade. This patient's clinical course is interesting because the thrombocytopenia developed as an isolated symptom at the age of 5 years and preceded the skin anomalies by three years. The diagnosis of dyskeratosis congenita was made only after an evolution of five years. The diagnosis of dyskeratosis congenita--although it is a rare disease--should be considered in every child first seen with aplastic anemia or thrombocytopenia.
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