Clinical and genetic spectrum of 104 Indian families with central nervous system white matter abnormalities.

Genetic disorders with predominant central nervous system white matter abnormalities (CNS WMAs), also called leukodystrophies, are heterogeneous entities. We ascertained 117 individuals with CNS WMAs from 104 unrelated families. Targeted genetic testing was carried out in 16 families and 13 of them received a diagnosis. Chromosomal microarray (CMA) was performed for three families and one received a diagnosis. Mendeliome sequencing was used for testing 11 families and all received a diagnosis. Whole exome sequencing (WES) was performed in 80 families and was diagnostic in 52 (65%). Singleton WES was diagnostic for 50/75 (66.67%) families. Overall, genetic diagnoses were obtained in 77 families (74.03%). Twenty-two of 47 distinct disorders observed in this cohort have not been reported in Indian individuals previously. Notably, disorders of nuclear mitochondrial pathology were most frequent (9 disorders in 20 families). Thirty-seven of 75 (49.33%) disease-causing variants are novel. To sum up, the present cohort describes the phenotypic and genotypic spectrum of genetic disorders with CNS WMAs in our population. It demonstrates WES, especially singleton WES, as an efficient tool in the diagnosis of these heterogeneous entities. It also highlights possible founder events and recurrent disease-causing variants in our population and their implications on the testing strategy.

Giant fibroadenoma of breast in an adolescent girl.

A 12-year-old girl presented with a 15 × 15 cm, rapidly enlarging mass in left breast. Fine-needle aspiration cytology showed a benign proliferative breast lesion. Total excision of the mass was done preserving nipple and areola. Histopathology features were suggestive of giant fibroadenoma with benign phyllodes.

Pesticide (endosulfan) levels in the bone marrow of children with hematological malignancies.

OBJECTIVES: (1) To confirm the presence of Pesticide (Endosulfan) residues in the bone marrow (BM) of children with acute hematological malignancies and compare them with controls. (2) To ascertain if children with Endosulfan in their marrow reside in areas sprayed with Endosulfan. STUDY DESIGN: Case control study SETTING: Pediatric oncology unit of a medical college teaching hospital in Dakshina Kannada district of Karnataka. SUBJECTS: 26 patients with proven hematological malignancy and 26 age matched controls suffering from benign hematological disease. METHODS: Endosulfan residues in the BM were estimated by gas chromatography mass spectrometry (Minimum detection limit 10ng/mL). The subjects geographical area of location (residence) was determined to see whether they belong to sprayed area or not. The Chi-square test was applied to see an association between exposure status and hematological malignancy. RESULTS: A total of 52 children were enrolled of which 26 were study cases and 26 were controls. Of the study and control groups, 84.7% ;and 73.1%, respectively were from exposed areas. The major (88.4%) illness in the study group was ALL, while ITP (50%) occurred most frequently in the control group. Six out of 26 study cases tested positive for endosulfan in the BM, against 1 out of 26 controls (P = 0.042). The Odds ratio was 7.5. All children who had endosulfan in the bone marrow originated from areas, where endosulfan is still being used. CONCLUSIONS: Children with hematological malignancy had raised levels of endosulfan in the bone marrow compared to those without. All the children with raised bone marrow Endosulfan levels were found to be from areas exposed to the pesticide.

Oral artesunate for neonatal malaria.

A 24-day male baby presented with a history of fever and poor feeding. The baby was pale and had hepatosplenomegaly. Peripheral blood films revealed Plasmodium vivax. Chloroquine is the drug of choice in neonatal malaria. However, our patient did not respond to chloroquine. There has been very little experience with other drugs. This case highlights the use of oral artesunate to which the baby responded. The future may see its more frequent use in resistant malaria.

Hyperleukocytosis in a neonate: A diagnostic dilemma.

A preterm baby presented with lethargy and tachypnea. Blood counts revealed hyperleukocytosis. Peripheral smear and bone marrow examination were not suggestive of leukemia. The baby was treated for sepsis. The baby recovered and WBC counts gradually reduced. Hyperleukocytosis was presumed to be a part of leukemoid reaction secondary to sepsis. The diagnostic possibilities with a review of literature are also presented.

Significance of C-reactive protein during febrile neutropenia in pediatric malignancies.

Fifty episodes of febrile neutropenia (FN) in 33 children with malignancies were studied to evaluate the usefulness of C-reactive protein (CRP) levels as an indicator of infection, and the efficacy of antibiotic therapy. Nineteen FN episodes occurred in children with documented infection whereas, 9 and 22 episodes occurred with probable infection and fever of unknown origin, respectively. CRP positivity during episodes of documented and probable infection was significantly higher than with febrile episodes of unknown origin. Blood culture was positive in 15 episodes; of these, CRP was positive in 11. CRP declined to normal on 7th day of antibiotic therapy. CRP is a useful indicator of infection in neutropenic children and also in determining the efficacy of antibiotic therapy.