Protein C congenital deficiency. A case report

Protein C is a plasmatic protein that is synthesized by the liver with the help of vitamin K. It regulates thrombin formation and consequently prevents thrombosis. We present a case of a newborn male with change in the color of the right foot index finger who after 4 h showed cyanosis that reached malleolus level. Upon admission we observed generalized pallor, tachycardia and a necrotic lesion in the rightfoot. We suspected a septic process and thus administered cefotaxime, vancomycin and heparin. Platelet levels were 70,000 mm3, thromboplastin 16/12 sec., partial thromboplastin 5829 sec. PCfunctionality 20% and protein S 100%. Even though the patient evolvedfavourably and showed partial recovery, an intratuberous amputation was needed. One year later a prosthesis was fitted. We need to carry out studies that support the use of PC monoclonal antibodies in order to offer better baseline treatment to patients with PC congenital deficiency and improve their quality of live.     

A case of hyperalphalipoproteinemia with complete deficiency of cholesteryl ester transfer activity]

A 68-year-old male patient with benign hypertension shows high levels of high density lipoprotein cholesterol (HDL-C) of 171 mg/dl. The serum total cholesterol was 240 mg/dl. An abnormal slow alpha band and polydisperse low density lipoprotein (LDL) bands were detected by agarose gel and polyacrylamide gel electrophoresis. The slow alpha band was considered as an apo E-rich HDL. A peak of large HDL particle and a peak of abnormal high-molecular-LDL particle were observed in the patient's serum by gel permeation high performance liquid chromatography. Cholesteryl ester transfer activity (CETA) of the patient's serum was completely deficient (0.0%/10 microliters/18 hr). From these results, it is strongly suggested that patient's hyper-HDL-cholesterolemia caused by a complete deficiency of CETA.     

A case of pycnodysostosis with growth hormone deficiency

Pycnodysostosis is a skeletal dysplasia characterized by short stature. Treatment of pycnodysostosis with growth hormone (GH) has not been reported so far. We describe a case of pycnodysostosis with growth hormone deficiency in addition to low mean insulin-lüce growth factor 1 (IGF-1) concentration. Complete GH deficiency was determined by two pharmacological provocative tests (insulin and L-dopa). A good height-velocity response was obtained after GH replacement treatment. Pycnodysostosis with GH deficiency and replacement therapy have not been reported previously, to the best of our knowledge.     

A case of hereditary combined deficiency of complement components C6 and C7 in man.

Nine patients with a lymphoproliferative disorder characterized by a persistent expansion of large granular lymphocytes (LGL) and an increased proportion of cells labelling with natural killer (NK) and T cell markers were identified. The six patients with an expansion of alpha beta CD3/TcR positive cells were shown to have rearranged T cell receptor (TcR) genes whereas three patients whose LGL lacked CD3/alpha beta TcR on the surface had no beta TcR rearrangement detected. Eight of the nine patients were shown to exhibit non-MHC-restricted cytotoxic activity against K562; this activity was inhibited by CD45 and CD45-associated monoclonal antibodies known to inhibit normal non-MHC-restricted cytotoxicity but not specific MHC-restricted cytotoxic T cell activity. In contrast, the CD3 monoclonal antibody OKT3 did not inhibit but redirected LGL non-MHC-restricted cytotoxicity against K562. Following modulation of the CD3 molecule, the LGL were still capable of cytolysis of K562 targets, but additional OKT3 could no longer redirect cytolysis. The data indicate that the CD3/TcR complex on the LGL clones in patients with large granular lymphoproliferative disease is not the receptor for antigen on K562 cells, although it retains functional capabilities. Thus the CD3/TcR positive subset appears to have bipotential cytotoxic characteristics involving additional unique receptors for non-MHC-restricted cytotoxicity.     

A case of Sj?gren's syndrome associated with chronic hepatitis C and sarcoidosis]

A 68-year-old female had been treated for chronic type C hepatitis at our department since June, 1992. In August of the same year, swelling of the right eyelid developed and she was diagnosed as having sarcoidosis on the basis of uveitis, skin lesions, and bilateral hilar lymphadenopathy (BHL) on chest X-ray. With steroid therapy, the symptom improved and BHL disappeared. In July, 2001, dryness of the mouth and dry eyes developed, and she was diagnosed as having Sj?gren's syndrome (SjS). This case may be precious in discussing the pathophysiology of sarcoidosis and SjS including the association with hepatitis C virus infection.     

A case of Goldenhar syndrome associated with growth hormone deficiency

Summary We have experienced the case of a 10-year-old boy who had Goldenhar syndrome accompanied by growth hormone (GH) deficiency. His height increased after treatment with growth hormone was administered. We found no untoward effects of the hormone and we consider that treatment with GH is useful for patients who present with Goldenhar syndrome associated with growth hormone deficiency.     

A case of apolipoprotein C-II deficiency with coronary artery disease

A 56-year-old male with apolipoprotein C-II deficiency experienced a myocardial infarction without pancreatitis. A coronary angigram showed complete occlusions of both the right and circumflex coronary arteries. His serum lipid levels were as follows: fasting total cholesterol 3.15 mmol/l; postprandial total cholesterol 3.62 mmol/l; fasting triglycerides 1.46 mmol/l; postprandial triglycerides 6.14 mmol/l; fasting high-density lipoprotein-cholesterol 0.47 mmol/l; and postprandial high-density lipoprotein cholesterol 0.36 mmol/l. His fasting level of plasma apolipoprotein C-II was 0.0005 g/l, but his plasma levels of other apolipoproteins were within normal ranges. A DNA sequence analysis of the apolipoprotein C-II gene showed no mutations in exon 1, 2, 3, or 4, where most gene mutations related to apolipoprotein C-II deficiency occur. We report this patient's very rare heterozygous apolipoprotein C-II deficiency with coronary artery disease. Although this patient had some risk factors for coronary artery disease, coronary atherosclerosis in this patient might have occurred as a result of lipoprotein abnormalities caused by at least one mutation in the apolipoprotein C-II gene. Received: 7 May 2001 / Accepted: 30 January 2002     

C5a-inhibitor deficiency in peritoneal fluids from patients with familial Mediterranean fever

Normal peritoneal fluid contains an inhibitor of neutrophil chemotaxis that acts by antagonizing the complement-derived chemotactic anaphyllatoxin C5a. The inhibitor resembles a substance previously described in synovial fluids and is a protein with a molecular weight of approximately 40,000 as determined by gel filtration. In contrast, levels of inhibitory activity in peritoneal fluids from five patients with familial Mediterranean fever were decreased to less than 10 per cent of those found in normal subjects. Gel filtration of peritoneal and synovial fluids from these patients did not yield any fraction with inhibitory activity. We suggest that C5a-inhibitor deficiency in joint and peritoneal fluids from patients with familial Mediterranean fever may have a role in the pathogenesis of the inflammatory attacks characteristic of this disease.     

Falsely normal C4 in a case of acquired C1 esterase inhibitor deficiency

A 59-year-old lady presented with recurrent angioedema without urticaria. The clinical history and examination were consistent with an acquired C1 esterase deficiency secondary to lymphoproliferative disease. Despite a low C1 esterase level, the C4 level assayed by nephelometry on our automated analyser was normal. Analysis using different nephelometric analysers revealed consistently low C4, despite consistent normal readings in our analyser. Further investigation revealed an IgM-kappa paraprotein that seemed to interfere with both this and haematology coagulation assays. Splenic marginal zone lymphoma was confirmed on bone marrow biopsy. Monoclonal paraproteins may interfere with nephelometric, turbidimetric and immunological assays in a non-antibody-specific manner and should be considered when there are unusual or unexpected results, particularly in a patient with lymphoproliferative disease.     

Post-vaccine glomerulonephritis in an infant with hereditary C2 complement deficiency: case study

We describe a case of a post vaccine immune complex-mediated glomerulonephritis in an infant with compound heterozygous mutations of C2 complement component gene, which is the first such case in the literature. The three and a half months old boy presented with clinical and laboratory signs of nephritic syndrome and was successfully treated with methylprednisolone. An explanation of such a clinical picture may lie in the interaction between C2 deficiency and vaccination.Nephritic syndrome may occur at any age, but is an uncommon finding in infants (1-6). It is caused by proliferative changes and inflammation in the glomeruli – proliferative glomerulonephritis (GN), which can be a primary/isolated disease or a consequence of a systemic disease. The most common types of primary proliferative GN in children are post-infectious GN, IgA nephropathy, and membranoproliferative GN, and the most common types of proliferative GN due to a systemic disease are Henoch Schönlein GN and lupus GN (1,5,6). All these conditions are immunologically mediated with in situ immune-complex formation or passive immune-complex trapping in the glomeruli and activation of secondary immune mechanisms like complement system.We describe a case of presumably post-vaccine immune-complex mediated GN in a three and a half months old boy in whom two heterozygous mutations on a C2 complement component gene were found. The possible adverse event after vaccination was reported to the National Institute of Public Health.     

A new case of congenital ficolin-3 deficiency with primary immunodeficiency

ABSTRACT

Objectives

Human Ficolin-3 (FCN3) is an oligomeric-structured lectin encoded by the FCN3 gene with a pivotal role in the lectin complement pathway. It has anti-microbial activities against bacterial and viral infections and restrains opportunistic pathogens. Mutation in the FCN3 gene is associated with variable clinical manifestations particularly immunologic (infections and autoimmunity) and neurologic complications.     

A case of congenital factor V deficiency

A case of Factor V deficiency, the first case in Korea, is reported in a 9-year-old boy whose plasma concentration of Factor V was 6%. He complained of easy bruisability, prolonged bleeding from the mouth after minor trauma and hemarthrosis and flexion contracture of the right knee. His parents are heterozygous (maternal Factor V concentration 52%, paternal 40%).     

C5 deficiency in A/J mice is not associated with resistance to the development of secondary amyloidosis.

The aim of the study was to determine whether C5 deficiency in the mouse is associated with resistance to the development of secondary amyloidosis. Chronic inflammation was induced in the F2 progeny, derived from matings between amyloid-susceptible and amyloid-resistance mice, by daily injections of azocasein for thirty days. Using a restriction fragment length polymorphism generated by digestion of genomic DNA with the restriction enzyme HindIII, C5 sufficient and deficient DNA can be clearly differentiated. Eight mice were found to be C5 sufficient, 32 were heterozygotes and 14 were found to be C5 deficient. Grading of the splenic amyloid load from negative to 4+ was performed after staining tissue squashes with Congo red and viewing them under a polarizing microscope. Seventeen mice were noted to have negative to trace, 18 had moderate (1+ - 2+) and 19 had heavy (3+ - 4+) amyloid deposition. There was no correlation between splenic amyloid load and C5 deficiency. Based on these results it is clear that C5 deficiency and resistance to secondary amyloidosis are not associated.