Identification and characterization of 30 novel pathogenic variations in 69 unrelated Indian patients with Mucolipidosis Type II and Type III.

Mucolipidosis (ML) (OMIM 607840 & 607838) is a rare autosomal recessive inherited disorder that occurs due to the deficiency of golgi enzyme uridine diphosphate (UDP)- N-acetylglucosamine-1-phosphotransferase (GlcNAc-phosphotransferase) responsible for tagging mannose-6-phosphate for proper trafficking of lysosomal enzymes to lysosomes. Variants in GlcNAc-phosphotransferase (GNPTAB (α, ß subunits) and GNPTG (γ subunits) are known to result in impaired targeting of lysosomal enzymes leading to Mucolipidosis (ML) Type II or Type III. We analyzed 69 Indian families of MLII/III for clinical features and molecular spectrum and performed in silico analysis for novel variants. We identified 38 pathogenic variants in GNPTAB and 5 pathogenic variants in GNPTG genes including missense, frame shift, deletion, duplication and splice site variations. A total of 26 novel variants were identified in GNPTAB and 4 in GNPTG gene. In silico studies using mutation prediction software like SIFT, Polyphen2 and protein structure analysis further confirmed the pathogenic nature of the novel sequence variants detected in our study. Except for a common variant c.3503_3504delTC in early onset MLII, we could not establish any other significant genotype and phenotype correlation. This is one of the largest studies reported till date on Mucolipidosis II/III in order to identify mutation spectrum and any recurrent mutations specific to the Indian ethnic population. The mutational spectrum information in Indian patients will be useful in better genetic counselling, carrier detection and prenatal diagnosis for patients with ML II/III.

Comparison of the efficacy and safety of indomethacin, ibuprofen, and paracetamol in the closure of patent ductus arteriosus in preterm neonates - A randomized controlled trial.

INTRODUCTION: In this prospective study, we compared the efficacy and safety of ibuprofen, indomethacin, and paracetamol in the closure of patent ductus arteriosus (PDA) in preterm neonates. MATERIALS AND METHODS: This randomized prospective study was conducted in the Division of Pediatric Cardiology, M. D. M and Umaid Hospital, Jodhpur. A total of 105 preterm neonates with gestational age <37 weeks and hemodynamically significant PDA (hs-PDA) diagnosed clinically and confirmed by echocardiography were enrolled. All neonates were randomly assigned in a ratio of 1:1:1 to oral indomethacin (Group A, 3 doses at an interval of 12 h with a starting dose of 0.2 mg/kg), oral ibuprofen (Group B, 10 mg/kg ibuprofen followed by 5 mg/kg/day for 2 days), or IV paracetamol (Group C, 15 mg/kg every 6 hourly for 3 consecutive days). After the completion of the first course, neonates were assessed clinically as well as by echocardiography to confirm PDA closure. If PDA remained open, the second course of the same drug was given and repeat assessment was done within 24 h of the last dose. In addition to an echocardiographic examination, complete blood counts, renal and liver function tests were performed. RESULTS: Our study shows that there was no significant difference observed in PDA closure among all the three treatment groups after the completion of two courses of treatment. The cumulative rate of PDA closure was 68% in the indomethacin group, 77.14% in the ibuprofen group, and 71.43% in the paracetamol group (P = 0.716). There were no significant changes found in Hb, platelet, blood urea nitrogen (BUN), creatinine, and liver enzymes after treatment in the paracetamol group (P > 0.05). BUN and serum creatinine levels were significantly increased after treatment in indomethacin and ibuprofen groups (P < 0.0001 and P < 0.05, respectively). CONCLUSION: Our study shows that IV paracetamol is as effective as indomethacin and ibuprofen in promoting the closure of hs-PDA in premature infants with a better safety profile.

A fatal case of multi-organ failure in acute yellow phosphorus poisoning

Phosphorus is a nonmetallic irritant used in various sectors like rodenticide, firecracker industries, match industries, and fertilizers. Phosphorus poisoning is responsible for deaths among children and adults. Accidental yellow phosphorus poisoning is frequently reported in children, whereas suicidal consumption is not uncommon amongst adults. Herein, we present the case of a 30-year-old female patient who ingested Ratol paste containing yellow phosphorus in an attempt to commit suicide. Her initial chief complaints were nausea, vomiting along with loose motion during hospitalization, followed by a symptomless phase with stable vitals on the 2nd day, and managed conservatively. She took discharge against the medical advice. Later on, she was readmitted in the same hospital, after two days, complaining of generalized weakness, bodily pain, drowsiness, loss of appetite, and breathing difficulties. She developed severe complications due to the intoxication and died. An autopsy was performed. The histopathological and the toxicological examination were carried out. We found characteristic features in different organs due to yellow phosphorus toxicity. We concluded the cause of death as hepatic encephalopathy and multi-organ dysfunction syndrome caused by the yellow phosphorus poisoning.

A fatal case of multi-organ failure in acute yellow phosphorus poisoning.

Phosphorus is a nonmetallic irritant used in various sectors like rodenticide, firecracker industries, match industries, and fertilizers. Phosphorus poisoning is responsible for deaths among children and adults. Accidental yellow phosphorus poisoning is frequently reported in children, whereas suicidal consumption is not uncommon amongst adults. Herein, we present the case of a 30-year-old female patient who ingested Ratol paste containing yellow phosphorus in an attempt to commit suicide. Her initial chief complaints were nausea, vomiting along with loose motion during hospitalization, followed by a symptomless phase with stable vitals on the 2nd day, and managed conservatively. She took discharge against the medical advice. Later on, she was readmitted in the same hospital, after two days, complaining of generalized weakness, bodily pain, drowsiness, loss of appetite, and breathing difficulties. She developed severe complications due to the intoxication and died. An autopsy was performed. The histopathological and the toxicological examination were carried out. We found characteristic features in different organs due to yellow phosphorus toxicity. We concluded the cause of death as hepatic encephalopathy and multi-organ dysfunction syndrome caused by the yellow phosphorus poisoning.

Incidence of Congenital Hypothyroidism in Western Rajasthan Using Cord Blood Thyroid-stimulating Hormone Levels as a Screening Tool: A Cross-sectional Hospital-based Study.

BACKGROUND: Congenital hypothyroidism (CH) is considered the most common preventable cause of intellectual impairment, with a worldwide annual incidence of 1:4000 live births. In the absence of screening program actual incidence in India is not exactly known, but in previous studies it varies from 1:500 to 1:3400. We wished to find out the incidence of CH in Western Rajasthan using cord blood TSH as a screening tool and venous TSH within 14 days of life as a confirmatory test. METHODS: This cross sectional descriptive study was conducted over a period of six months in teaching hospitals attached to Medical College. Cord blood TSH value of 20 mIU/L or >20 mIU/L was taken as cut off for screening and all screen positive neonates were re-tested for serum TSH by taking venous samples within 14 days of life. Repeat TSH levels of 20mIU/L or more tested by Enzyme Linked Fluorescent Assay were considered confirmatory. RESULTS: Total 9558 cord blood samples were analyzed for TSH levels, out of which 533 came out to be screen positive (recall rate 5.57%). Out of these 58 could not be confirmed, so were excluded from the further analysis. Effective sample size and screen positive cases dropped to 9500 and 475 respectively, and out of these 13 were confirmed as CH (incidence - 1.37 per thousand live births). CONCLUSIONS: Considering the previous studies, incidence of CH is much higher in Western Rajasthan than the anticipated. Overall in India CH seems to be more prevalent than the other parts of the world, necessitating the need of national screening program.

Correlation of Serum Vitamin D Levels in Lactating Mothers and Their Infants.

BACKGROUND: Although Vitamin D deficiency is highly prevalent in Indians, data on Vitamin D eficiency in lactating mothers and exclusively breast fed infants is inadequate. OBJECTIVE: This study was done to evaluate the prevalence of Vitamin D deficiency in lactating mothers and their infants and to find out any correlation between them. MATERIALS AND METHODS: This hospital based, cross sectional study included 200 healthy infants between 1-30 days and their mothers. Serum sample was collected from both for Ca, inorganic phosphate (IP), alkaline phosphatase (ALP), and 25(OH)D. RESULTS: Mean serum 25(OH)D level of mothers was 11.33 ± 5.86 ng/ml with a range of 2-37 ng/ml. Hypovitaminosis D was defined as serum 25(OH)D level <10 ng/ml. Almost 94 (47%) of mothers were having hypovitaminosis D. Mean serum 25(OH)D level of infants was 11.92 ± 7.89 ng/dl with a range of 2.5-68 ng/dl. Ninety (45%) infants were having hypovitaminosis D. There was a moderate positive correlation between individual mothers' and infants' serum 25(OH)D values (Pearson coefficient = 0.516, P < 0.001). Using logistic regression, it was found that infants born to mothers with hypovitaminosis D carry a 4.47 times more risk of developing hypovitaminosis D as compared to infants born to mothers with normal serum 25(OH)D (Odds ratio = 4.47, P < 0.001). CONCLUSION: This study shows a high prevalence of Vitamin D deficiency in lactating mothers and their breastfeeding infants with a positive correlation between them. These results provide a justification for adequate Vitamin D supplementation of all exclusively breastfeeding infants and highlight the urgent need to improve maternal Vitamin D status.

Infantile Systemic Hyalinosis: Novel Founder Mutation in the Initiation Codon among "Malis (Farmers)" in Jodhpur.

Infantile systemic hyalinosis (OMIM 236490) is a progressive autosomal recessive disorder characterized by widespread deposition of hyaline material in many tissues leading to multiple subcutaneous skin nodules, gingival hypertrophy and joint contractures. The authors describe five children from four unrelated families, from the "mali (farmer)" community in Jodhpur, with the disorder. All of them had classical clinical features, and four died from severe infections between age of 7 mo to 3 y. Two affected children had the same, but novel mutation in the initiation codon, in homozygous form c.1 A > G; p. M1? in capillary morphogenesis protein-2 (CMG2), or ANTXR2 gene on chromosome 4q21.21. The other two parents had the same mutation in heterozygous form. It is likely that this is a founder mutation in this community.

Pneumocephalus in Child Following Bilateral Otomastoiditis and Nasal Septum Infection.

Pneumocephalus is collection of gas or air within the cranial cavity, commonly associated with trauma, cranial surgery, air embolism, open meningomyelocele; and rarely as a result of central nervous system infections. Asymptomatic pneumocephalus usually recovers spontaneously within few days. Untreated pneumocephalus can progress to tension pneumocephalus, manifesting as severe headache, dizziness, cranial nerve palsy, mental changes, seizure and disorientation. Herein, we report a rare case of pneumocephalus in a 9-month infant with subdural effusion following infection of nasal septum and otomastoiditis. There was no sign of meningitis but CThead showed communication of intracranial dura mater across widened foramen caecum with pre-nasal space, and bilateral otomastoiditis with erosion of anterior and lateral wall of right mastoid bone. The patient was treated successfully and discharged without sequelae.

Pneumopericardium due to ingestion of button battery.

Mostly ingested button batteries passed through the gastrointestinal tract without any adverse effects. But button battery can lead to hazardous complications including tracheoesophageal fistula (TEF), especially when the battery is impacted in the esophagus. Urgent esophagoscopic removal of the battery is essential in all cases. Once the TEF is identified, conservative management is the initial treatment of choice. Delayed primary repair can be tried if spontaneous closure does not occur. Here in we want to report a rare case of air leak syndrome, pneumo-pericardium secondary to the corrosive effect of a button battery and child recovered completely with conservative management.