Biomedical subjects
Publications and source records attributed to J Jaeken.
In this paper we report a second example of 13 trisomy mosaicism due to de novo 13/13 translocation followed by postzygotic fission of the translocation chromosome in a polymalformed female newborn.
We report on five girls (including monozygotic twins) with a newly recognized disease comprising severe neurologic disturbances, variable hepatomegaly, abnormal subcutaneous fat distribution and skeletal anomalies. The neurologic picture was characterized by moderate to severe psychomotor retardation, alternating internal strabismus , hypotonia, hyporeflexia and ataxia. Biochemical investigations showed a number of abnormalities such as tubular proteinuria, slightly increased serum transaminases, hypoalbuminemia, hypo-beta-lipoproteinemia and decreased serum thyroxine-binding globulin. Moreover there was retinitis pigmentosa, cerebellar hypotrophy and electrophysiologic evidence for a peripheral neuropathy. However, histologic examination of a nerve biopsy in one of the patients failed to show myelin abnormalities. On the other hand, abnormal lamellar inclusions were found in the lysosomes of some Schwann cells and of liver tissue as well. Additional investigations in four patients revealed a deficiency of sialic acid, galactose and N-acetylglucosamine of plasma glycoproteins. Enzymatic analysis of serum suggested a deficiency of an N-acetyl-glucosaminyltransferase. Remarkably, the (healthy) fathers but not the mothers presented the same carbohydrate deficiencies of plasma glycoproteins albeit to a much lesser degree. The mode of hereditary transmission of this disease remains unclear; the possibility of X-linked inheritance is under investigation.
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Clinical and biochemical data are presented on eight children with adenylosuccinase deficiency. This newly discovered inborn error of purine metabolism is characterized by an accumulation in body fluids of succinyladenosine (S-Ado) and succinylaminoimidazole carboxamide riboside (SAICA riboside), the dephosphorylated derivatives of the two substrates of adenylosuccinase. Six living children (three boys and three girls) and one deceased sibling displayed severe psychomotor retardation. Epilepsy was documented in five cases, autistic features in three, and growth retardation associated with muscular wasting in a brother and sister. In the cerebrospinal fluid, plasma and urine of these patients, the S-Ado/SAICA riboside ratio was between 1 and 2. In striking contrast, the eighth patient (a girl) was markedly less mentally retarded. Most noteworthy, the S-Ado/SAICA riboside ratio in her body fluids was around 5, suggesting that her milder psychomotor retardation was causally linked to this higher ratio. Adenylosuccinase deficiency was demonstrated in the liver of all seven living children, in the kidney of three patients in whom the enzymatic activity was measured, and in the muscle of three patients, including the two with muscular wasting. In fibroblasts of the six severely retarded patients, adenylosuccinase activity was reduced to approximately 40% of normal; in the patient with the higher S-Ado/SAICA riboside ratio, it reached only 6% of normal. The clinical heterogeneity of adenylosuccinase deficiency justifies systematic screening for the enzyme defect in unexplained neurological disease.
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Regional brain glucose utilization was investigated by positron emission tomography with fluorodeoxyglucose in three children with adenylosuccinase deficiency. A consistent pattern was found in the three patients, namely a marked decrease of fluorodeoxyglucose uptake in all gray structures, with the exception of the cerebellum, which was minimally affected. Anomalies predominated in the cerebral cortex, particularly in the anterior regions; they were less pronounced in thalamus and basal ganglia. The observations suggest that positron emission tomography may be a useful tool for the localization of the deleterious effects of metabolic diseases and for the investigation of their pathophysiologic mechanisms.
The case of a 30th week preterm newborn infant, ventilated because of hyaline membrane disease and presenting with localized stenoses of the carina involving both main-stem bronchi is described. The diagnosis was made on bronchoscopy and bronchography after a period of recurrent atelectases and lobar emphysema. Due to severe broncho-pulmonary dysplasia, surgical reconstruction was impossible. A balloon dilatation was successfully performed while the infant was still ventilated. He died however at the age of 180 days.
A partial trisomy of the long arm of chromosome number 3 (3q23----3qter) is reported in a malformed male newborn with a Pierre-Robin sequence. The importance of the detection of chromosomal abnormalities towards the nosology of malformation sequences is discussed.
A 46,XY/46,XY,r(4) mosaicism is described in a malformed male newborn with bilateral renal agenesis. A review of the phenotypic findings in the previously reported ring chromosome 4 patients is made and the importance of the detection of chromosomal abnormalities towards the nosology of malformation sequences is discussed.
In the present report we describe a complex chromosomal rearrangement, resulting in a distal 11p monosomy, in a 7-month-old severely retarded girl with a non-specific phenotype. In this complex chromosomal rearrangement chromosomes 11, 13 and 21 are involved in the translocation of the long arm of chromosome 21 on the short arm of chromosome 13 and translocation of the short arm and satellites of chromosome 21 on the short arm of chromosome 11.
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We report on 2 patients, less than age 5 years, and one adult patient with partial duplication 8p, due to interstitial duplication of bands 8p21.1-22. The phenotype in young and adult patients with this chromosomal unbalance syndrome is further documented. In young patients the craniofacial manifestations are very similar to trisomy 8 mosaicism. However, mental retardation is much more pronounced in 8p21-22 duplication than in trisomy 8 mosaicism. The phenotypic changes observed in adult patients are probably secondary and they are due to the great neurologic deficit with generalized spasticity and hypertonia.
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A Turkish girl presented with a history of fever, diarrhoea, convulsions, recurrent infections and failure to thrive from the age of 5 months. Megaloblastic anaemia was present and profound folate deficiency was evidenced in plasma and in CSF. Treatment with oral folic acid cured the anaemia, diarrhoea and infections but failed to prevent convulsions and the appearance of mental retardation and cerebral calcifications. Loading tests with folic acid and its derivatives led to the conclusion that the folate deficiency was caused by a defect in folate transport both across the gut and the blood-brain barrier. Low plasma concentrations of methionine prompted a therapeutic trial with methionine associated with vitamin B12 and folic acid that spectacularly improved the convulsions.