Huntington's disease: deterioration in clinical state during treatment with angiotensin converting enzyme inhibitor.
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Captopril↗
Biomedical subjects
J Goldblatt
Publications and source records attributed to J Goldblatt.
Molecular genetics and Huntington's disease. The South African situation.
The finding of a polymorphic DNA marker for Huntington's disease offers the potential for preclinical and prenatal screening for this condition. However, before implementation of a programme of this nature in South Africa, certain technical, medical psychosocial and ethical considerations require careful appraisal. The current situation with regard to the importance and implications of this new technology to affected kindreds is reviewed and discussed.
DNA↗
Familial rhizomelic dysplasia: phenotypic variation or heterogeneity?
In a consanguineous kindred of mixed ancestry in Cape Town we observed a boy with severe shortness of stature and an unusual skeletal dysplasia with marked shortness of the humeri. A male one-half second cousin had gross abnormalities of the lower limbs, which were worst in the femora, but his skeleton was otherwise virtually normal. A brother and sister of this latter individual had been similarly affected and their parents were consanguineous. The question arises as to whether two similar but separate disorders are present in this family or whether the condition in these two persons represents extreme phenotypic variability of the same autosomal recessive entity.
Bone Diseases, Developmental↗
Unique skeletal dysplasia with absence of the distal ulnae.
We report on an Indian woman with a severe shortness of stature, absence of the distal ulnae, and a predominantly spondylometaphyseal skeletal dysplasia. The clinicoradiographic changes in this patient appear to represent a unique skeletal disorder.
Abnormalities, Multiple↗
New autosomal dominant radial ray hypoplasia syndrome.
Radial ray anomalies can occur as isolated defects [Temtamy and McKusick, 1978] or as components of genetic syndromes, which are delineated on the basis of the associated anomalies, inheritance, chromosome, or hematological abnormalities. Syndrome identification is important because of the prognostic implications of the particular hematologic, oncologic, and clinical complications specific for each condition. In some instances overlap and variable expression of the manifestations associated with the radial ray defect confuse nosological definition and genetic counselling. In this paper we describe a father and his 2 daughters, who manifested variable defects of the radial ray and concurrent choanal malformations and esotropia. This apparently autosomal dominant condition differs from other radial ray hypoplasia disorders with respect to the associated anomalies and the absence of any hematologic or chromosomal aberrations.
Abnormalities, Multiple↗
Heterozygous manifestations of Langer mesomelic dysplasia.
The mesomelic dysplasias are a heterogeneous group of genetic disorders with predominant skeletal manifestations in the forearms and shanks. We have documented, over a thirteen-year period, the clinical and radiographic course of the condition in a boy with the Langer type of mesomelic dysplasia. It has been suggested that dyschondrosteosis or the Madelung deformity are the phenotypic manifestations of the gene which causes Langer mesomelic dysplasia in the homozygote. Several relatives on both sides of the family which we studied had malformations of their forearms, in keeping with this concept. However, these anomalies differed from those of dyschondrosteosis and the classical Madelung deformity; the exact syndromic status of the heterozygous phenotype remains unsettled.
Adolescent↗
Autosomal recessive inheritance of idiopathic dilated cardiomyopathy in a Madeira Portuguese kindred.
Cardiomyopathy is a heterogeneous disorder with numerous inherited and acquired causes. Familial, isolated, dilated cardiomyopathy is usually reported as being inherited in an autosomal dominant mode with variable penetrance and expressivity. In this paper we describe a form of autosomal recessively inherited, dilated, cardiomyopathy occurring in three members of a consanguineous Madeira Portuguese family. Following review of the literature, it appears that the autosomal recessive form of dilated cardiomyopathy is more common than previously reported.
Adult↗
Ehlers-Danlos syndrome: yet another type?
A mother and her four children had gross generalized joint laxity, with multiple dislocations and subluxations, moderate skin hyperextensibility and mild connective tissue fragility. Their condition could be categorized in the Ehlers-Danlos syndrome Type III or the familial undifferentiated hypermobility group of disorders, but differed from these conditions by virtue of the severity of articular complications and the presence of wormian bones in the skulls. We consider that these patients have an undelineated connective tissue disorder; attempts at characterization at the molecular level are underway.
Adult↗
Spinal cord decompression for Gaucher's disease.
We report an individual with Type I nonneuronopathic Gaucher's disease who experienced the rare complication of spinal cord compression secondary to a sclerotic vertebral fracture. He successfully underwent anterolateral spinal cord decompression and spinal fusion despite the severity of his generalized skeletal disease.
Gaucher Disease↗
A new hypospadias-mental retardation syndrome in three brothers.
Three brothers had a syndrome of hypospadias and mental retardation in association with microcephaly, craniofacial dysmorphism, joint laxity, and beaked nails. No other family members were affected, and this previously undelineated condition appears to be inherited in either an autosomal recessive or X-linked recessive mode.
Child↗
Occult life-threatening streptococcal septicaemia in the elderly. A report of 2 cases.
Streptococcal septicaemia may occur as a fulminant illness, which has a reported mortality rate in excess of 80%. The organism is, however, usually highly sensitive to penicillin and prompt diagnosis and initiation of therapy should reduce this. Two patients with streptococcal septicaemia who presented in shock, initially thought to have a primary vascular cause, are reported. The course of the disease illustrates the importance of recognizing the protean modes of presentation of this condition and of starting appropriate therapy before laboratory confirmation of the diagnosis.
Aged↗
Autosomal recessive idiopathic torsion dystonia in a kindred of mixed ancestry.
A family with idiopathic torsion dystonia (dystonia musculorum deformans) was seen in a peripheral clinic in the Richtersveld in the north-western Cape. This rare inherited form of neurological disease has maximal prevalence in individuals of Ashkenazi Jewish ancestry, and there is controversy regarding the exact mode of inheritance. The kindred documented in this study was of mixed ancestry (Cape Coloured), and autosomal recessive inheritance was suggested by the finding of affected male and female siblings born to normal parents in an isolated inbred community.
Adolescent↗
Tricho-rhino-phalangeal syndrome without exostoses, wih an interstitial deletion of 8q23.
We report on a patient with the Tricho-Rhino-Phalangeal syndrome (TRPS) with normal mentation, without exostoses and with a partial microdeletion of 8q23. Although she had the phenotypic characteristics of TRPS Type I, karyotypic analysis demonstrated the 8q-microdeletion usually associated with TRPS Type II, in which exostoses are present. Our patient represents the second reported instance of this phenotypic chromosomal association and provides further evidence for homogeneity of the TRPS.
Abnormalities, Multiple↗
Gaucher's disease type 1: assessment of bone involvement by CT and scintigraphy.
The effectiveness of CT and technetium-99m sulfur colloid (99mTc SC) bone-marrow scans in determining the extent and severity of skeletal involvement in 23 patients with type 1 Gaucher's disease was compared with the effectiveness of conventional radiographic techniques and technetium-99m methylene diphosphonate (99mTc MDP) bone scintigrams. Density measurements obtained by CT proved sensitive in differentiating normal marrow (-50 to -120 H). Scintigrams with the sulfur colloid nuclide demonstrated three distinct patterns of uptake: peripheral expansion of normal marrow (profile B), greater marrow expansion with patchy areas lacking uptake (profile C), and greater loss of uptake with retention of the nuclide in other reticuloendothelial organs and circulation (profile D). CT scans provided greater sensitivity in resolving the extent of marrow involvement in affected areas, while the 99mTc SC scintigrams were more effective in overall assessment of the severity of bone-marrow involvement. Both conventional radiographic techniques and 99mTc MDP bone scans were useful primarily as screening procedures or for evaluating specific involved areas. 99mTc MDP scans were useful in evaluating regional defects (i.e., ischemic necrosis) in certain cases, but no consistent patterns were observed. CT and 99mTc SC scans are useful for determining the extent and severity of Gaucher's disease involvement of bone marrow.
Bone Diseases↗
Retinitis pigmentosa in South Africa.
Retinitis pigmentosa (RP), the commonest inherited form of blindness, is a heterogeneous condition which usually manifests as an isolated abnormality, but is occasionally a component of various rare syndromes. The basic defect in RP is unknown, but the recent molecular genetic discovery of linkage with a restriction fragment length polymorphism in X-linked RP offers the potential for carrier screening and antenatal diagnosis of this form of the disorder. In this article we present an overview of RP and an analysis of our findings from a questionnaire survey of 130 affected individuals in 63 families in the Cape Province and Natal. The proportions of the different genetic types of RP were generally in accordance with those found in overseas studies, being 14% autosomal dominant, 9,5% autosomal recessive and 6% X-linked recessive. A further 35% of the affected persons had RP together with other syndromic stigmata, while the remaining 35% could not be classified into any specific genetic category.
Female↗
Genetic heterogeneity in Gaucher disease: physicokinetic and immunologic studies of the residual enzyme in cultured fibroblasts from non-neuronopathic and neuronopathic patients.
To elucidate the genetic heterogeneity in the three major phenotypic subtypes of Gaucher disease, the residual acid beta-glucosidase in fibroblasts from patients with all three subtypes from different ethnic and demographic groups was investigated by comparative kinetic, thermostability, and immunotitration studies. The kinetic studies delineated three distinct groups (designated A, B, and C) of residual activities with characteristic responses to the enzyme modifiers, taurocholate (or phosphatidylserine), and glucosyl sphingosine (or N-hexyl glucosyl sphingosine); Group A residual enzymes responded normally to these modifiers. All neuronopathic patients (types 2 and 3) and most non-Jewish, non-neuronopathic patients (type 1) had group A residual activities and thus could not be distinguished by their kinetic properties. Group B residual enzymes had markedly abnormal responses to these modifiers. All Ashkenazi and only two non-Jewish type 1 patients had group B residual activities. Group C residual activity had an intermediate response to all modifiers and represented a single Afrikaner type 1 patient. Pedigree studies indicated that this patient was a genetic compound for the group A (type 2) and group B (type 1) mutations. Thermostability studies showed additional heterogeneity of the residual activities within the three kinetic groups. Group A (type 2) and group B (type 1) enzymes had similarly decreased thermostabilities. In contrast, group A (type 1) residual activities were heterogeneous; three classes of thermostabilities were found among these enzymes: normal, decreased, and increased. Immunotitration of equal amounts of the normal or Gaucher disease beta-glucosidase activities with monospecific IgG indicated that the enzyme proteins from most Gaucher disease patients were antigenically altered and/or that large amounts of catalytically abnormal or inactive antigen were present. A decreased amount of antigenically and catalytically normal enzyme was present in a group A, type 1 African black patient, suggesting decreased stability or synthesis of his mutant acid beta-glucosidase. These kinetic, immunologic, and thermostability studies indicated that 1) type 1 Gaucher disease is biochemically heterogeneous and results from at least four distinct allelic acid beta-glucosidase mutations that alter enzyme structure and/or function, 2) neuronopathic and non-Jewish non-neuronopathic phenotypes cannot be distinguished reliably by kinetic analyses alone, and 3) the Ashkenazi type 1 Gaucher disease results from a unique mutation that alters a specific active site domain of acid beta-glucosidase.
Cells, Cultured↗
Obstetric aspects of Gaucher disease.
The medical aspects of 21 pregnancies in 11 women with type I, non-neuronopathic Gaucher disease have been reviewed. One pregnancy ended in a spontaneous abortion at 12 weeks and two pregnancies in one patient resulted in two children with the Hurler syndrome which is unrelated to Gaucher disease. The other 18 pregnancies resulted in the birth of normal infants at full-term, four by caesarean section and the remainder by normal vaginal delivery. Only one patient experienced a significant exacerbation of her Gaucher disease during pregnancy. Fifteen of the pregnancies were associated with mild haematological complications but active intervention was necessary in only two instances. It can be concluded that there are few contraindications to pregnancy in women with Gaucher disease.
Abortion, Spontaneous↗
Immune thrombocytopenia and Gaucher's disease.
A 35-year-old Ashkenazi woman with Gaucher's disease was evaluated for persistent thrombocytopenia. The diagnosis of Gaucher's disease was made by bone marrow aspiration and confirmed by the determination of glucocerebrosidase levels in leukocytes and cultured skin fibroblasts. Studies of platelet-associated IgG and in vivo platelet survival demonstrated immune-mediated destruction of platelets consistent with immune thrombocytopenic purpura. A trial of prednisone had no effect on the platelet count. Total splenectomy resulted in a complete and prolonged remission. The clinical implications of Gaucher's disease and concurrent immune thrombocytopenic purpura are discussed.
Adult↗