Homozygous mutations in NTRK1 gene underlie congenital insensitivity to pain with anhidrosis in Pakistani families

Congenital insensitivity to pain with anhidrosis is a rare autosomal recessive disorder presenting with loss of pain sensation, thermal sensation defects, and self-mutilating behavior. In the present study, we recruited two consanguineous pedigree showing pain insensitivity symptoms from Pakistan for clinical and molecular investigations. In family A, one female patient displayed classical CIPA symptoms along with microcephaly and severe intellectual disability. During course of the disease, her right foot was amputated and had remarkable dental degeneration and teeth shedding. In family B, one boy presented with classical symptoms of congenital insensitivity to pain with anhidrosis. Blood was collected from both families for molecular studies. Sequencing with the Ilumina Trusight One Sequencing Panel covering 4813 OMIM genes revealed a known homozygous mutation c.2084C>T; p.P695L of NTRK1 in family A and a novel truncated mutation c.2025C>G; p.Y681X in family B. Protein modeling analysis of both mutations (p.P695L and p.Y681X) predicted loss of the rigidity in tyrosine kinase domain of NTRK1 that led to conformational changes as well as deleterious effect on protein function. The known mutation was reported more than a decade ago in a family from Northern Israel and other non-sense mutation is newly identified. It is interested that most of NTRK1 mutations are associated with this domain. This is first ever report of NTRK1 variants in congenital insensitivity to pain with anhidrosis patients from Pakistan.

Acute organophosphate insecticide poisoning

To describe the clinical course, diagnosis, out come of acute organophosphate [OP] insecticide poisoning. Descriptive study. At National Poisoning Control Centre [NPCC], Medical unit 1, Jinnah Post Graduate Medical Centre, Karachi, from 1st January 2000 to 31st December 2007. A total of 6539 pts were admitted to the ICU of NPCC, out of which 2708 [41%] were of organophosphate poisoning. Lab investigations done included blood complete picture, urea, creatinine, ABG's and serum cholinesterase levels. Data was retrieved from the files on a structured performa. Variables of the study include gender, mode of exposure, clinical course, management and complications. There were 1391[51%] were males and 1317 [48%] females. 713 [26%] had accidental exposure, while 1995 [73%] attempted suicide. The majority of patients exhibited the classic clinical features of parasympathetic over activity. 1608 patients received atropine, while pralidoxime alone was given to only 399 patients and atropine along with pralidoxime was given to 701 patients. Complications encountered during their treatment and stay in the hospital included aspiration pneumonia observed in 310 patients, hyperglycemia in 982 patients. 102 patients had respiratory failure and thus required mechanical ventilation with mean ventilation duration of 2.3 +/- 1.5 days. 500 patients had urinary tract infection and 789 patients developed cellulitis or phlebitis. A total of 147 patients died making a mortality rate of 0.05%. The widespread use of organophosphates as a household and agricultural pesticide, in the absence of adequate regulations and education in their use is probably the most important reason for OP poisoning in an agricultural country like Pakistan. Despite severe toxicity in most of our cases, there were very few fatalities. This reflects the necessity of early diagnosis, treatment and the implementation of advanced supportive care in ICU

Group A sterptococcal sepsis and osteomyelitis of the skull in a neonate with cephalohematoma: a case report

Infected cephalohematoma may lead to osteomyelitis of the skull in a neonate. It is a rare entity which is difficult to diagnose clinically. A case report of skull osteomyelitis is presented. A 33 day old girl of African origin born by ventouse extraction came with breathing difficulty, high grade fever up to 104 F, excessive crying and poor feeding for the previous 4 days. The mother noted a scalp swelling present since birth which gradually increased in size over the last 10 days and was discharging pus. Examination showed an irritable baby with tachycardia, tachypnea and fever of 102 F. Oxygen saturation was 92% in room air. There was a large scalp swelling 6x4 cm in size on right parietal area. It was tense, indurated and tender to touch with three pus discharging lesions. Anterior fontanelle was soft and not bulging. Rest of the examination was normal. Initial investigations and chest x-ray were normal. Skull Xray showed erosion of the parietal bone proximal to the soft tissue swelling. Empirical intravenous antibiotics included ceftazidime, cloxacillin and amikacin. Blood culture done at admission revealed Group A Streptococcus after 48 hours. A localized pus swab and aspiration fluid from cephalohematoma revealed serous aspirate that was culture negative. The baby improved clinically with resolution of cephalohematoma after 10 days. She received intravenous cloxacillin for 3 weeks. She was followed up in clinic and had remained well since discharge. Neonates can develop skull osteomyelitis. Group A streptococcus may be implicated along with other microorganisms. Skull x-rays are suggestive whereas CT scan is diagnostic. Prompt antibiotics and surgical drainage will have successful outcome

Management of pediatric HCV

Hepatitis C viral [HCV] infection is emerging as a challenge to the developing and affluent nations alike including the pediatric population. With universal pretransfusion screening for HCV, the major focus of pediatric HCV disease has shifted to the study of natural course and management of perinatally acquired HCV disease. In contrast to the favorable change of trend in the developed countries, sharing of contaminated needles and instruments, unprotected sex and occupational exposure continue to be a significant source of transmission in developing countries like Pakistan. Similarly, there is a lack of epidemiological data and a new sense of urgency in the healthcare community about the burden of the pediatric HCV disease for the local population in Pakistan. In general, the course of HCV infection is deceptively benign during childhood followed by complications during later life including hepatocellular carcinoma [HCC] and end stage liver disease. Interferon and more recently Pegylated-interferon [PEG-INF] with ribavirin has gained popularity as the treatment modalities in adults. However, there is lack of consensus guidelines for screening and management of HCV during childhood. Cost is an additional barrier to pharmacotherapy in developing countries. This review focuses on the natural history, diagnostic modalities and approach to the management of HCV in pediatric age group

Antenatal screening for infectious diseases in Pakistan: an effective preventive opportunity

Infections during pregnancy are common and have potentially adverse effects on the fetus. A variety of bacterial, viral and parasitic infections are known to cause profound and long-term effects on both the mother and the unborn baby. Clinical features, extent and long term consequences depend on each infecting organism. Exact diagnosis can be difficult in most instances. Newer and better diagnostic modalities are now available for early antenatal screening. In a country like Pakistan infectious diseases are predominant cause of morbidity and mortality during pregnancy. The exact burden of each of these in pregnancy is not defined but is probably substantial. We will discuss here some of the available literature and the common infections that may be targeted for antenatal screening in Pakistan

Management of pediatric HCV

Hepatitis C viral [HCV] infection is emerging as a challenge to the developing and affluent nations alike including the pediatric population. With universal pretransfusion screening for HCV, the major focus of pediatric HCV disease has shifted to the study of natural course and management of perinatally acquired HCV disease. In contrast to the favorable change of trend in the developed countries, sharing of contaminated needles and instruments, unprotected sex and occupational exposure continue to be a significant source of transmission in developing countries like Pakistan. Similarly, there is a lack of epidemiological data and a new sense of urgency in the healthcare community about the burden of the pediatric HCV disease for the local population in Pakistan. In general, the course of HCV infection is deceptively benign during childhood followed by complications during later life including hepatocellular carcinoma [HCC] and end stage liver disease. Interferon and more recently Pegylated-interferon [PEG-INF] with ribavirin have gained popularity as the treatment modalities in adults. However, there is lack of consensus guidelines for screening and management of HCV during childhood. Cost is an additional barrier to pharmacotherapy in developing countries. This review focuses on the natural history, diagnostic modalities and approach to the management of HCV in pediatric age group

Congenital tuberculosis revisited: a case report and recent review of literature

Perinatal tuberculosis, including congenital tuberculosis, is rare. It is a difficult disease to diagnose in the neonatal period. There should be high index of suspicion in a neonate with sepsis-like presentation, non-resolving pneumonia or unexplained illness. Fatality is high if there is a delay in diagnosis. Improved screening of women at risk and awareness is thus essential. This case illustrates the importance of history of maternal illnesses and evaluation including endometrial biopsy; neonatal gastric aspirates for acid-fast bacilli smears and cultures and polymerase chain reaction for diagnosis. Early institution of therapy has successful outcome. A recent review of literature of congenital tuberculosis is also presented

Targeting zero measles in Pakistan: time to change the EPI schedule

Measles is a highly contagious disease with significant morbidity and mortality. Major epidemics have continued to occur over the last decade in many regions of the world. These epidemics have occurred in non-vaccinated and vaccinated children as well as in adults. Low vaccination coverage rates, receipt of less than two doses of measles vaccine, waning immunity and vaccine failures have been the main factors in the resurgence of measles. Health authorities have focused on different ways to reduce the transmission of this vaccine-preventable disease. In most industrialized countries high vaccine coverage [>80-90%], good surveillance and a two-dose vaccine strategy have reduced measles burden. High vaccination coverage and changing to a two-dose measles vaccination will greatly reduce disease transmission in endemic regions. World Health Organization's Expanded Program for Immunization has been modified to include two-dose measles coverage in some regions. In Pakistan the Expanded Program for Immunization also needs to be modified to adopt a 2-dose measles vaccination schedule