Sudha Rao

Increased activation of the alternative complement pathway in sickle cell disease

Complement proteins play an important role in host defenses against Streptococcus pneumoniae, a major cause of serious infections in sickle cell (SS) disease. Previous studies have suggested abnormalities of the alternative complement pathway in SS disease. We measured activation of the alternative pathway in sera from patients with SS disease utilizing an enzyme immunoassay which detects C3b,P complexes, derivative of the C3b,Bb,P alternative pathway convertase. In all, 89% of SS sera had elevated concentrations of C3b,P complexes, indicative of increased alternative pathway activation. Chronic activation of the alternative pathway may contribute to impaired host defense in SS patients.

Twin fetus in fetu

Fetus in fetu is a rare cause of intra-abdominal mass. The presence of vertebral and skeletal axis differentiates it from a teratoma.1 We report an unusual case of two well developed fetuses in the retroperitoneal area of a neonate delivered at term.

INCREASED CHROMOSOME FRAGILITY OF DONOR CELLS IN FANCONI'S ANEMIA AFTER BONE MARROW TRANSPLANTATION

Bone marrow transplantation appears to be an effective method of treatment of cases of Fanconis anemia (FA) in the aplastic phase. A 20 year old Hispanic female with FA was successfully treated by bone marrow transplantation from her sister as donor. There was a polymorphism involving chromosome 20 between the donor and the recipient. Following the successful engraftment, karyotypes prepared from the blood of the recipient (presumably donor cells) had the karyotype of the donor. The chromosome breakage rate of the recipient before radiation and marrow transplant was 10.9 breaks per 100 mitotic cells using mitomycin C technique. The breakage rate of the donor before transplant was 2.0. Following the transplantation procedure, lymphocytes from the recipient (presumably donor cells) had a breakage rate of 9.8. These clinical and experimental findings suggest that a plasma or other marrow micro-environmental factor in FA may be responsible for the increased chromosomal fragility previously observed in this disease.

Neonatal Diabetes with Intractable Epilepsy: DEND Syndrome

Permanent Neonatal Diabetes Mellitus (PNDM), is a rare monogenic disorder, caused by activating mutations of the KATP channel. The most severe clinical form of PNDM presents as Developmental delay, Epilepsy and Neonatal Diabetes (DEND) syndrome. Diagnosis is confirmed by genetic mutation testing. Oral sulfonylurea therapy improves neurological outcome.

Unusual manifestations of henoch-schonlein purpura

Henoch schonlein syndrome (HSP) represents a diagnostic challenge when gastrointestinal symptoms or other atypical symptoms precede the cutaneous manifestations. We describe two patients whose abdominal symptoms antedated cutaneous manifestations. Six-year-old, black male patient, presented with 1 wk history of vomiting (without diarrhea or urinary symptoms), hypertension (140/90 mmHg), diffuse abdominal pain and hypoactive bowel sounds:. WBC’s 40,000/Cu mm3 with 80 percent hypoproteinemia, (albumin 1.6 G%), high plasma renin and stools positive for occult blood. Renal function and urinalysis was normal. Two weeks later patient developed urticarial purpuric rash over the ankles, gross hematuria and gross edema. Biopsy of the skin lesion was consistent with HSP vasculitis. Second patient 4 yr Brazilian male patient presented with abdominalpain, vomiting, blood in the stools, and pain in the right testis. Three days later, developed purpuric rash over his limbs and trunk. He also had hypoproteinemia, hypoalbuminemia, leukocytosis and normal urine analysis. Abdominal pain, bloody stools, painful testicular swelling and hypoproteinemia abated with steroid therapy. In HSP patients, atypical presentation of abdominal pain, hypertension, hypoproteinemia without proteinuria testicular swelling and leucocytosis in the absence of cutaneous and joint manifestations poses as diagnostic problem. Protein-losing enteropathy should be considered in HSP patients with hypoproteinemia.

Identification of Novel Mutations in STAR Gene in Patients with Lipoid Congenital Adrenal Hyperplasia: A First Report from India

Lipoid congenital adrenal hyperplasia (LCAH), a rare disorder of steroid biosynthesis, is the most severe form of CAH. We report novel molecular findings of three unrelated infants with LCAH diagnosed at our center. A known missense mutation c.653C>T (p.A218V) and two novel mutations [premature termination c.441G>A (or p.W147X) and frameshift deletion c.del815G (or p.R272PfsX35)] were identified after complete sequencing of the STAR gene. Prenatal diagnosis was carried out for the family with mutation c.815delG by molecular testing wherein the fetus was found to be homozygous for the mutation. This is the first report of molecular diagnosis and prenatal testing for LCAH from India. Conflict of interest:None declared.

H. INFLUENZA B IMMUNIZATION OF CHILDREN WITH SICKLE CELL DISEASES

H. flu B vaccine is recommended for children 1.5-6 yrs with sickle cell anemia but the adequacy of their response is unknown. We immunized 55 children age 1.5-5.6 yrs (mean 3.6) with sickle cell syndromes, ss, sc or s-thal using two vaccines alternately, single blind (25 patients PRP; 30 PRP-D). The vaccine groups were similar in age, sickle diagnoses and vaccine-to-post-serum interval (28-57 days, mean 40). Coded pre and post sera were tested by radioimmunoassay for ug/ml of anti-PRP antibody.The geometric mean titer (GMT) for the entire group of children rose 48 fold from 0.126 (PRP, 0.158; PRP-D, 0.104) to 6.16 (PRP, 2.45 or 16 fold vs. PRP-D, 12.88 or 123 fold; p=.006, p=.001 for fold rise difference). A total of 34 children (16 PRP; 18 PRP-D) with pre titers <0.125 rose 80 fold from a GMT of 0.045 (PRP, 0.046; PRP-D, 0.044) to 3.60 (PRP, 1.35 or 30 fold vs. PRP-D, 8.51 or 195 fold; p=.019, p=.025 for rise). Eighty-eight, 68 and 28% of PRP children and 100, 97 and 60% of PRP-D children achieved titers of≥0.1, ≥1.0 and≥5.0 respectively. Only 5% or 16% of the total group ended up with possibly inadequate titers <0.1 or<:1.0 respectively.Thus both vaccines were immunogenic in most sickle cell children and are likely to protect. However, PRP-D appears to be more immunogenic than PRP in our population at 1-2 mos after vaccination.

Unusual Presentations of Posterior Fossa Tumors in Children

Case 1 An 8 years old boy came with 8 days’ history of vertigo which exacerbated on lying down, frequent falls and bitemporal headache. Temperature, blood pressure, tone and power were normal, but limb reflexes were brisk. Cerebellar signs of dysdiadochokinesia, past pointing and tandem walking were positive. No signs of raised intracranial pressure (ICP) were present. MRI brain revealed diffuse pontine glioma.

FETAL HEMOGLOBIN LEVELS IN CORD BLOOD

Cord blood electrophoresis normally reveals high levels of Hb F with smaller amounts of Hb A. At the University of Illinois Comprehensive Sickle cell Center, 9,832 consecutive cord bloods were screened since October 1983 by both Cellulose acetae and Citrate agar electrophoreses. These included infants of all ethnic groups. Of the tested infants, 21 had Hb F as the sole detectable hemoglobin. These included 14(66%) preterm infants. Cesarian section was performed for varying reasons in 6 instances. Mothers of 2 infants had gestational diabetes as per glucose tolerance tests; 4 mothers were chronic asthmatics on long-term bronchodilator therapy during pregnancy;4 were habitual drug abusers (heroin and marijuanna) even during pregnancy; three mothers had chronic hypertension, one of these was preeclamptic; and one mother had chronic renal insufficiency requiring hemodialysis 3 times per week and frequent blood transfusions. Almost half the mothers smoked ½-1 pack cigarettes/day. Multiple parameters including expected date of delivery, gestational age of infant per physical exam, placental weight, birth weight, mothers gravida and para status were studied but found to be of no significance. High fetal hemoglobin in cord blood has been well described in infants of mothers with chronic anoxemia during pregnancy as well as in infants of diabetic mothers. As 7 of the 21 mother-infant cases studied in this group had no identifiable factors, we speculate that there might be yet other determinants influencing expression of hemoglobin patterns at birth.

Retrospective analysis of 58 children with retinoblastoma

We performed a retrospective analysis of 58 children with retinoblastoma seen at the University of Illinois at Chicago between 1960 and 1982. Our findings showed an almost equal distribution by sex, a predominance (69%) of white patients, and a common presenting symptom (70%) of leukocoria, with (22%) or without (48%) strabismus. Unilateral involvement was noted in 35 patients (60%). Of the 23 (40%) bilaterally affected children, 19 had simultaneous involvement at the time of diagnosis. All bilateral and 90% of the unilateral cases were diagnosed before age five years. Family history was positive for retinoblastoma in five bilateral and one unilateral case. At the time of diagnosis, 35 patients had stage V disease (Reese-Ellsworth classification, Table 1). Depending on the stage of disease treatment included enucleation, radiation, and chemotherapy. Mortality was 25% from 1960 to 1974, and zero thereafter.