Congenital Factor V Deficiency

A 14-month-old girl suffering from a heavy bleeding tendency, caused by a severe isolated congenital factor V deficiency is described. In this study 56 family members were examined. 10 of them had a factor V level ranging 26–60% of the normal – these were classified as heterozygotes. The case histories of the heterozygotes did not reveal a bleeding tendency. The inheritance of this factor V deficiency is autosomal recessive, with varying expressivity in the heterozygotes.     

Congenital Deficiency of Factor XIII in an Indian Kindred

Deficiency of factor XIII was detected in an 18-year-old man. During a study of 64 members of his kindred, 2 additional cases were documented. In these 3 cases the onset of symptoms and the clinical course varied considerably. The proband had no abnormal bleeding till the age of 8 years. His 11-year-old sister bled from the umbilical stump on the fifth day, but has had no abnormal bleeding since then. The parents of these siblings are second cousins. The third patient, 10 months of age, also bled from the umbilical stump on the fifth day and she has continued to have significant haemorrhagic problems. Her parents are first cousins. In each of the two affected families, one other daughter had died following haemorrhage from the umbilical stump. The pattern of inheritance is consistent with an autosomal recessive mode of transmission.     

Congenital Deficiency of Proconvertin: A Clinical and Laboratory Report

1. A case of congenital deficiency of proconvertin in a Hopi Indian boyis reported. This is the eleventh case of "pure" proconvertin deficiency and thesecond reported in the American literature.

2. Laboratory studies revealed normal intrinsic blood coagulation butmarkedly abnormal tests when coagulation was studied in the presenceof tissue extracts.

3. An accompanying mild deficiency of prothrombin was suggested bythe results of some tests.

4. The concept that the role of proconvertin in hemostasis is primarilyas a co-thromboplastin is supported by the clinical and laboratory studiescarried out on this patient. The differentiation of this disorder from othercases with deficiencies of "serum" factors is discussed, and the previously reported cases are reviewed.

Submitted on November 12, 1958 Accepted on March 9, 1959     

Congenital Deficiency of Cyclo-Oxygenase in a Woman with Generalized Atherosclerosis

The case of a 52-year-old woman with congenital cyclo-oxygenase deficiency, signs of generalized atherosclerosis and a moderate bleeding tendency is reported. Secondary platelet aggregation was absent. Platelet aggregation induced by arachidonic acid failed totally while that induced by calcium ionophore was normal. No malondialdehyde formation could be detected in her platelet-rich-plasma. The life-long deficiency of cyclo-oxygenase had not protected her from progressive vascular disease. This case suggests that the chronic intake of large doses of aspirin cannot prevent arterial disorders.     

先天性肾上腺皮质增生症：非经典型21羟化酶缺陷症的研究进展

先天性肾上腺皮质增生症(congenital adrenal hyperplasia,CAH,OMIM 201910)是一组常染色体隐形遗传疾病,因为皮质醇、醛固酮等类同醇激素合成路径中酶的缺陷所致.21羟化酶缺陷症(Deficiency of 21-Hydroxylase,21OHD)是其中最常见的类型,约占90%～95%.追溯CAH的历史,自1563年发现肾上腺后,1865年意大利解剖学家De Crecchio在尸体解剖中发现一个外观为"男性"的人具有女性的内生殖器和增生的肾上腺,首次将肾上腺增生及CAH联系起来,之后经过多年的研究才逐渐明确了其病理生理机制为21OHD.     

Congenital Vascular Defect Associated with Platelet Abnormality and Antihemophilic Factor Deficiency

1. A kindred of 311 individuals, many members of which are affected by ahemorrhagic diathesis, has been described.

2. The variability in the manifestations of this diathesis is extreme. Inits fullest expression the disease is characterized by a prolonged bleeding timewith evidence of a morphologic defect in the platelets, and a deficiency inantihemophilic globulin. Some possibly affected individuals exhibit only aprolonged bleeding time, while, on the other hand, the clinically most severelyaffected individual, with AHF levels on several occasions of 5 to 10 per cent,has not been observed by us to have a prolonged bleeding time, although hisplatelets are morphologically abnormal.

3. Genetic analysis suggests that the hemorrhagic tendency is determinedby a single dominant gene of variable penetrance and expressivity.

4. No satisfactory explanation can be developed on the basis of these studiesfor the association between platelet abnormality and AHF deficiency. Morespecifically, it is impossible to conclude whether the platelet defect is precursor to the AHF deficiency, or whether—as on a priori grounds seems lesslikely—this is an example of true genetic pleiotropy.

5. The terminologic chaos which afflicts the literature on hemorrhagicdiatheses characterized by a prolonged bleeding time is discussed in the lightof the findings in this one large kindred, and suggestions are advanced forminimizing confusion based on terminology alone.

Submitted on July 27, 1959 Accepted on November 8, 1959     

Congenital Haemorrhagic Condition Similar but Not Identical to Factor X Deficiency

A 23-year-old white male with a bleeding tendency since early childhood presented a congenital coagulation defect similar but not identical to factor X deficiency. A first and second stage defect were demonstrated, characterized by a prolonged prothrombin time, prolonged partial thromboplastin time, abnormal thromboplastin generation, abnormal prothrombin consumption. The Stypven clotting time was slightly prolonged on fresh plasma but was normal on frozen plasma. Factors I, II, V, VIII, IX, XI, and XII were all within normal limits; factor VII was at the lower limits of normally or slightly decreased. Mr. Stuart's plasma failed to correct the defect of the patients plasma; however, a known factor VII deficient plasma was able to correct the abnormality. Factor X levels showed low (3–13%) only when assayed using tissue whole thromboplastin or tissue partial thromboplastin; the factor X assay using a Stypven-cephalin mixture yielded normal or near normal values. The factor II + factor X level using a Stypven-cephalin mixture appeared normal also. The significance of the findings is discussed. The results are tentatively interpreted as being due to an abnormal factor X rather than to a real deficiency.     

Evidence for Forebrain Cholinergic Neuronal Loss in Congenital Ornithine Transcarbamylase Deficiency

Congenital ornithine transcarbamylase (OTC) deficiency in humans results in failure to thrive, hypotonia, seizures and mental retardation. Neuropathologic evaluation reveals significant cerebral cortical atrophy, delayed myelination and Alzheimer type II astrocytosis. Using an animal model of congenital OTC deficiency, the sparse fur (spf) mouse, studies reveal convincing evidence of a loss of forebrain cholinergic neurons in this condition. Evidence includes (i) reduced activities of the cholinergic nerve terminal enzyme choline acetyltransferase (ChAT), (ii) a 25% loss of ChAT immunostaining, (iii) reduced high affinity transport of [³H]choline by cortical synaptosomes and (iv) a selective reduction in densities of presynaptic muscarinic M₂ binding sites, inspf mouse brain compared to controls. A partial correction of the cholinergic deficit was observed following treatment with acetyl-L-carnitine. Possible mechanisms responsible for cholinergic neuronal loss in congenital OTC deficiency include decreased synthesis of the ChAT substrate acetyl CoA, impaired cerebral energy metabolism and NMDA receptor-mediated excitotoxicity. Loss of forebrain cholinergic neurons is consistent with the severe cognitive impairment characteristic of congenital OTC deficiency.     

A Case of Congenital Atypical Haemolytic Anaemia with Pyruvate Kinase Deficiency

The authors describe a female patient with congenital non-spherocytic haemolytic anaemia (type I, DACIE).
The most characteristic biochemical properties are a markedly decreased pyruvate kinase activity and a lowered ATP content of the erythrocytes.

Résumé

Les auteurs décrivent une patiente avec une anémie congénitale non sphérocytaire (type I de DACIE).
Les propriétés biochimiques les plus caractéristiques sont une diminution marquée de l'activité de la pyruvate kinase et une contenance plus basse en ATP de ces érythrocytes.

Zusammenfassung

Die Autoren beschreiben eine Patientin mit kongenitaler nicht-sphärozytärer hämolytischer Anämie (Typ I nach DACIE). Die charakteristischen biochemischen Anomalien waren eine deutlich herabgesetzte Aktivität der Pyruvatkinase sowie ein verminderter ATP-Gehalt der Erythrozyten.     

Factor V Deficiency Associated with Congenital Cardiac Disorder and Intracranial Hemorrage

Factor V deficiency is an inherited disorder, in which the clotting factor V is low. The disorder is very rare, occurring in only one in one million people. It is inherited as an autosomal recessive disorder. The results of coagulation studies include a prolonged prothrombin time and partial thromboplastin time associated with reduced plasma factor V content. Patients with factor V deficiency have a hemophiliac like hemorrhagic disorder. Epistaxis, bruising, and menorrhagia are some of the common features. If treatment is needed, fresh frozen plasma is typically given. In this report we present a 12 year old girl who was admitted to our clinic with recurrent nosebleeds and intracranial hemorrage after head trauma. After examination, factor V deficiency was diagnosed. She also had congenital cardiac disorder (VSD), probably a co-incidental finding.     

Haptoglobin: A Review

Whereas a considerable body of information concerning haptoglobin is available, some very basic questions remain to be answered. These include the site and rate of haptoglobin synthesis, its role in normal metabolism, the fine structure of the haptoglobin molecules, mechanisms influencing their polymerization, and the selective advantages, if any, associated with the various phenotypes.

Résumé

Malgré le bagage considérable des connaissances acquises concernant les haptoglobines, certaines questions prirαordiales restent sans réponse, telles que l'endroit et le degré de leur synthase, leur rôle dans le métabolisme normal, la structure intime des molécules d'haptoglobines, Ies mécanismes qui influencent leur polymérisation et les avantages, s'il y en a, qui sont liés aux différents phénotypes.

Zusammenfassung

Trotz der heute vorliegenden umfangreichen Kenntnisse über das Haptoglobin weiß man noch nichts sicheres über den Ort und die Geschwindigkeit seiner Synthese, über seine physiologische Bedeutung im Stoffwechsel, seine Feinstruktur und die Mechanismen der Polymerisierung sowie über allfällige Auslesevorteile der ver-schiedenen Hp-Phänotypen.     

Methemoglobin Reductase (Cytochrome b5 Reductase) Deficiency in Congenital Methemoglobinemia

Two NADH diaphorases, diaphorase I andII, were isolated from normal red cells andcongenital methemoglobinemic red cellsby CM-cellulose and DE 32 column chromatography. For methemoglobinemicsample, activities of diaphorase I and diaphorase II were 80% and less than 5% ofthose for the normal red cells, respectively.Only diaphorase II showed cytochrome b₅reductase activity. The cytochrome b₅ reductase deficiency seems to manifestmethemoglobinemia through the decreasein the enzymatic reduction of cytochromeb₅ and subsequent nonenzymatic reduction of methemoglobin by the reducedcytochrome b₅. The methemoglobinemicdiaphorase II was found similar to thenormal enzyme with respect to Kms forthe dye and NADH, heat stability, effectof pH, and electrophoretic pattern. Theratio of the diaphorase activity to the cytochrome b₅ reductase activity was the samefor both enzymes. Although the productionof an abnormal enzyme molecule can notbe excluded, it is possible that in thiscase the rate of enzyme formation is decreased.

Submitted on October 10, 1973 Accepted on May 30, 1974