Impaired IgG responses in a child with homozygous C2 deficiency and recurrent pneumococcal septicaemia

Homozygous deficiency of the second component of complement (C2) is the most common inherited deficiency of complement. Although C2 deficiency has been detected in asymptomatic individuals, patients usually present with either autoimmune disease or recurrent pyogenic infection, particularly due to encapsulated bacteria such as Streptococcus pneumoniae, Haemophilus influenzae type b and Neisseria meningitidis. Interestingly, infection is the most common mode of presentation of C2 deficiency in young children (1). An association between C2 deficiency and IgG subclass deficiency has also been previously described. We now report a female child with C2 deficiency that presented at the age of 3 mo with recurrent pneumococcal septicaemia. Although IgG subclass levels were normal, specific IgG responses to vaccination against S. pneumoniae and H. influenzae were significantly impaired.     

Variable immunologic deficiency syndrome in a 10 1/2-year-old girl with Haemophilus meningitis

A 10 1/2-year-old girl with Haemophilus-meningitis was found to have hypogammaglobulinemia. Further immunologic evaluation revealed common variable immunodeficiency. Patients suffering from severe or recurrent infections should always be suspected to have immunodeficiency disease.     

Recurrent pneumococcal meningitis in a patient with transient IgG subclass deficiency

We report the case of a 3 year old boy who exhibited recurrent serious infections with a transient imbalance of IgG subclass in the second year of life. He suffered from pneumococcal meningitis at 3 months, hepatitis at 9 months, and purulent arthritis at 11 months of age. The second episode of pneumococcal meningitis occurred at 14 months. Serum IgG level was normal for age. Low level of IgG2, undetectable level of IgG4 and negligible level of pneumococcus-specific IgG1-G2 antibodies were found. No other primary immunodeficiency was apparent. Serum IgG2-G4 levels but not pneumococcus-specific IgG1-G2 titers increased by the age of 30 months. At that time, he was inoculated with a polyvalent pneumococcal vaccine along with acellular diphtheria-pertussis-tetanus vaccine. He acquired the immunity against these agents, and had no episodic infections in the following 2 years. This observation stresses the existence of transient IgG subclass deficiency associated with delayed development of the anti-polysaccharide antibody response.     

Long-term survival of a child with homozygous protein C deficiency successfully treated with living donor liver transplantation

Abstract:  Homozygous protein C deficiency is an autosomal recessive disorder often presenting with purpura fulminans. Fresh frozen plasma and oral anticoagulation have been used in the treatment of this disease. Lately, protein C concentrate has become the treatment of choice. However, protein C concentrate is not yet widely available in many countries. We report a six-month-old girl with homozygous protein C deficiency who had suffered from frequent thrombotic episodes. She was successfully treated with living donor liver transplantation. Eight years after the transplantation, she remains symptom free. As described here, the liver transplantation offers an alternative curative treatment for children with homozygous protein C deficiency.     

A neonate with homozygous protein C deficiency with a homozygous Arg178Trp mutation

Homozygous protein C deficiency affects approximately 1/400,000 to 1/1,000,000 live births. Homozygous protein C deficiency is associated with catastrophic and fatal purpura fulminans-like or thrombotic complications and disseminated intravascular coagulation. In the present patient, genetic study revealed Arg178Trp, a mutation found widely in European population; but this is the first case of homozygous Arg178Trp mutation who suffered from catastrophic purpura fulminans phenotype.     

Recurrent systemic bacterial infections in homozygous C2 deficiency

Homozygous deficiency of the second component of complement (C2) occurs in one in 10, 000 individuals. Its clinical manifestations range from essentially no symptoms to recurrent infections or evidence of collagen-vascular disease. We present here a case report and a review of the literature focusing on recurrent systemic infections in C2-deficient individuals. Thirteen of 20 patients vi'ith C2 deficiency and a history of invasive bacterial infections have had recurrent episodes of bacteremia or meningitis. Most of these patients were children, and Streptococcus pneumoniae was the most common pathogen reported. The use of prophylactic antibiotics. Haemophilus influenzae type b and pneumococcal vaccines, and prompt medical attention for any febrile illness should be encouraged in children with documented C2 deficiency. Although there are no studies to date to document their efficacy, the above measures may serve to diminish the frequency of recurrent systemic bacterial disease in these children.     

Fatal gastric perforation in a 4-year-old child with a late-presenting congenital diaphragmatic hernia

A previously well 4-year-old male presented with a 2-day history of listlessness, anorexia, left upper quadrant pain, and vomiting followed by sudden cardiorespiratory arrest and death. At autopsy a 50-mm diameter congenital defect in the posterolateral part of the left diaphragm was discovered associated with herniation of the stomach, spleen, greater omentum, and portions of the transverse colon and pancreas into the chest cavity. Perforation of the anterior wall of the stomach had filled the pleural cavity with gastric contents. This case demonstrates that not all late presenting congenital diaphragmatic hernias have a benign clinical outcome, and emphasizes the need for an increased awareness of this rate but potentially curable entity. Offprint requests to: R. W. Byard     

Porphyria cutanea tarda in a 4-year-old child with uroporphyrinogen decarboxylase deficiency

A 4 years old girl presents a typical case of patent form of cutaneous late porphyria with a reduced activity of the erythrocyte, uroporphyrinogen decarboxylase (UROD) genetically transmitted over 3 generations; a multifactor inheritance (HLA A3, a normal phenotype of alpha 1 antitrypsin, exogenous toxins, or viral infections) is discussed.     

Diagnosis and treatment of a newborn with homozygous protein C deficiency

The case is reported of a seriously affected newborn with homozygous protein C deficiency who developed neonatal purpura fulminans. Foetal ultrasound at 33 wk of gestation revealed ventriculomegaly. The first lesions appeared on the scalp 48 h after birth. She was initially treated with fresh-frozen plasma and, after the diagnosis was confirmed, with purified protein C concentrate. After skin necrosis had healed, therapy was continued with oral warfarin. The infant was homozygous for protein C W380G mutation. Diagnosis at the DNA level gave the parents an option of reliable prenatal diagnosis in their subsequent pregnancy. CONCLUSION: Difficulties in reaching an accurate diagnosis are discussed since early diagnosis and urgent therapy with protein C replacement are crucial to avoid further damage after delivery.