Seip M, Trygstad 0. Generalized lipodystrophy, congenital and acquired (lipoatrophy) Acta Pediatr 1996; Suppl413:2-28. Stockholm. ISSN 0803-5326 This review is based on longitudinal studies on our seven patients with congenital generalized lipodystrophy, our patient with acquired generalized lipodystrophy, and published papers on these subjects. An inability to store energy in adipose tissue is of pathogenetic importance. In congenital lipodystrophy, insulin resistance is present from birth, resulting in hyperinsulinaemia, dyslipidaemia, and insulin-resistant diabetes with an anabolic syndrome worsened by a voracious appetite. Clinically. we observed increased height velocity in pre-school age children, and organomegaly with hypertrophic cardiomyopathy, which seems to be lethal in early adulthood: three of our patients died at the ages of 24,32 and 37 years. The oldest alive, 39 years, suffers from stenocardia. Regarding treatment, it is most important to reduce energy consumption. The congenital form is recessively inherited. The aetiology may be related to insulin receptor or postreceptor mechanisms. Acquired generalized lipodystrophy seems to be an autoimmune disorder with secondary destruction of the adipose organ; the anabolic syndrome with insulin-resistant diabetes is secondary. Our patient died when 24 years old from pneumonia. 0 Acanthosis nigricans. anabolic syndrome, generalized lipodvstrophy, h~vpermetaholism, hypertrophic cardiomyopathy , lipoatrophic diabetes 0 Trygstad, Department of Paediatrics, Rikshospitalet. N-0027 Oslo, Norway cr) Scandinavian University Press 1996. ISSN 0803-5253 Generu1i:ed lipodwtrophy 3 ACTA PEDIATR SUPPL 413 (1W6) Tuhle 1. Main clinical features in generalized lipodystrophy. Congenital type ( Berurdinelli-Seip syndrome) 1. 2. 3. 4. 5. 6. 7. Extreme paucity of fat in subcutaneous and other adipose tissues, with insulin resistance, hyperinsulinaemia, hypertriglyceridaemia, and non-ketotic diabetes Voracious appetite and hypermetabolism, hyperhidrosis An anabolic syndrome with increased height velocity, advanced bone age. muscular hypertrophy, masculine body build, acromegaloid stigmata, organomegaly, enlarged genitalia in infancy, abundant hair of the scalp, hypertrichosis Hypertrophic cardiomyopathy (serious) Acanthosis nigricans Often mild mental retardation Hypothalamic-pituitary dysfunction Acquired type (Seip-Lowrence svndronte)

Summary. Investigations of the haemostatic functions in three patients with the Wiskott‐Aldrich syndrome are presented. All patients had severe thrombocytopenia and prolonged bleeding times. The platelets had abnormal morphology with reduced size and variations of shape. Electron microscopy revealed ultrastructural abnormalities with a reduced number of organelles, and many of the platelets contained large numbers of tubules. Platelet electrophoretic mobility in citrated plasma was not reduced by collagen, and platelet aggregation by collagen and ADP was deficient. Biochemical studies revealed a lack of the storage pool of adenine nucleotides. Platelet adhesiveness in vitro in whole blood was reduced. Platelet factor‐3 release by kaolin, ADP and freezing and thawing was normal in one and reduced in another of the patients. Platelet survival studies showed a normal survival time of normal donor platelets in one patient, while autologous platelets had a markedly reduced survival time in two of the patients. The bone marrow contained normal numbers of megakaryocytes. By electron microscopy of the bone marrow, blood platelets were found to be phagocytosed by macrophages and reticulum cells. The main cause of the thrombocytopenia is most probably incrcased peripheral destruction of platelets. It is suggested that the qualitatively defective platelets are recognized in the reticulo‐endothelial system as foreign particles and phagocytosed.

We have fully characterized two alpha thalassaemia mutants that occur in Southeast Asia, - -THAI and - -FIL. Each mutant is due to a deletion that removes the entire zeta-alpha-globin gene complex. Localization of the 5' breakpoints described here, allows the identification of unique fragments that are specific for each of the two mutations. This information can be used to assess the frequency of these mutants in Southeast Asia and will be of value in prenatal testing for alpha thalassaemia in this area.

No abstract

Pyrimidine 5 nucleotidase (P5N-1) deficiency is an autosomal recessive condition causing hemolytic anemia characterized by marked basophilic stippling and the accumulation of high concentrations of pyrimidine nucleotides within the erythrocyte. It is implicated in the anemia of lead poisoning and is possibly associated with learning difficulties. Recently, a protein with P5N-1 activity was analyzed and a provisional complementary DNA (cDNA) sequence published. This sequence was used to study 3 families with P5N-1 deficiency. This approach generated a genomic DNA sequence that was used to search GenBank and identify the gene for P5N-1. It is found on chromosome 7, consists of 10 exons with alternative splicing of exon 2, and produces proteins 286 and 297 amino acids long. Three homozygous mutations were identified in this gene in 4 subjects with P5N-1 deficiency: codon 98 GAT3GTT, Asp3Val (linked to a silent polymorphism codon 92, TAC3TAT), codon 177, CAA3TAA, Gln3termination, and IVS9-1, G3T. The latter mutation results in the loss of exon 9 (201 bp) from the cDNA. None of these mutations was found in 100 normal controls. The DNA analysis was complicated by P5N-1 pseudogenes found on chromosomes 4 and 7. This study is the first description of the structure and location of the P5N-1 gene, and 3 mutations have been identified in affected patients from separate kindreds. ( IntroductionPyrimidine 5Ј nucleotidase (P5ЈN-1, also known as uridine-5Ј-monophosphate hydrolase-1) catalyzes the dephosphorylation of the pyrimidine 5Ј monophosphates UMP and CMP to the corresponding nucleosides. A deficiency of this enzymatic activity was first identified by Valentine et al 1,2 in erythrocyte stroma while investigating patients with hemolytic anemia characterized by marked basophilic stippling. Initial studies showed very high concentrations of what were assumed to be adenine nucleotides in the erythrocytes, but these were later found to be pyrimidine nucleotides; the red blood cells (RBCs) also contained high levels of glutathione and reduced activity of ribose-phosphate pyrophosphokinase. Studies on 3 additional kindreds with hemolytic anemia and basophilic stippling demonstrated absent or markedly reduced pyrimidine 5Ј nucleotidase activity in their RBCs. 3 Reports of 40 patients with this condition have been published, with presumably large numbers undetected. However, because of the lack of a simple and reliable test for carriers, the exact prevalence of the condition is unknown. Reported numbers of homozygotes suggest that it is the third most common RBC enzymopathy-after glucose-6-phosphate dehydrogenase and pyruvate kinase deficiency-causing hemolysis. 4 Although the first 6 patients reported were all female, a number of affected males have been reported since then, and the pattern of inheritance is typical of an autosomal recessive disorder. 5 Additional studies have suggested that there are 2 isozymes of P5ЈN in RBCs, one with a preference for UMP and CMP, referred to as P5ЈN-1, and one able to hydrolyze deoxypyrimid...