Nuclear Mitochondrial Disorder Due to a Variant in NAXE in Two Unrelated Indian Children.

Progressive encephalopathy with brain edema and/or leukoencephalopathy type 1 (PEBEL1) is a nuclear mitochondrial disorder involving the NAD(P)HX repair mechanism due to a NAXE variation. PEBEL1 is characterized by rapid neurologic deterioration culminating in death following high-grade fever during infancy. Currently, 23 patients from 14 families are described in the literature, with only three survivors. The authors report two living children from unrelated families with PEBEL1. Both children presented in infancy with ptosis, squint, and ataxia with no skin manifestations. Whole-exome sequencing revealed previously reported c.804_807delInsA (p.Lys270del) variation in exon 6 of NAXE. This is the first Indian report of PEBEL1.

Acute Bacterial Meningitis and Petrous Apicitis in a Child with Aplasia Cutis Congenita: A Case Report.

Petrous apicitis and acute bacterial meningitis are uncommon in the present antibiotic era. The diagnosis of petrous apicitis is seldom considered unless there is cranial nerve palsy. A young child with aplasia cutis congenita presented with acute bacterial meningitis and an incidental opacified left mastoid in brain imaging. During the course, fever persisted, and high-resolution temporal bone imaging showed rapid progression to coalescent mastoiditis, petrous apicitis with erosions of tegmen tympani, and petrous apex. Other findings included bony dehiscences and thinning of left calvaria. Tympanomastoid exploration showed herniated brain and cerebrospinal fluid leak through tegmen tympani, which was closed with temporalis fascia graft. Herein, we report a rare presentation of petrous and tegmen erosion along with aplasia cutis congenita and discuss the challenges in diagnosis and management.

Tissue plasminogen activator receptor ANXA2 and its complementary regulator anti-inflammatory ANXA1 as prognostic indicators of inflammatory response in COVID-19 pathogenesis.

COVID-19 patients demonstrating hyperactive immunologic response appear to have a severe illness with a poor prognosis. This study hypothesizes that the pro-inflammatory Annexin A2 (ANXA2) has role in COVID-19 pathogenesis. In thisobservational study, serum levels of ANXA2 along with interleukin 1 beta (IL1ß), IL6, tumour necrosis factor-alpha (TNFα), and anti-inflammatory ANXA1 were determined by sandwich ELISA in 20 each control, mild, moderate, and severe COVID-19 subjects.The ANXA2 levels (130 ng/mL, p < 0.001) were significantly elevated in severe COVID-19 subjects, compared to mild, moderate and controls. Similarly, all the other pro-inflammatory biomarkers levels were also significantly correlated with disease severity (p < 0.0001). However, ANXA1 showed significantly negative correlation with disease severity (p < 0.0001). Furthermore, the pro-inflammatory ANXA2 showed utility in mortality prediction with 86% sensitivity and specificity, and 57% positive predictive value at a serum threshold of 94 ng/mL. Overall,ANXA2 and ANXA1 along with IL1ß, IL6, TNFα, would be beneficial biomarkers in assessing the COVID-19 severity and mortality prediction.

Exome Sequencing in Monogenic Forms of Rickets.

OBJECTIVE: To understand the phenotypic and genotypic spectrum of genetic forms of rickets in 10 families. METHODS: Detailed clinical, radiographic, and biochemical evaluation of 10 families with phenotypes suggestive of a genetic cause of rickets was performed. Molecular testing using exome sequencing aided in the diagnosis of six different forms of known genetic causes. RESULTS: Eleven disease-causing variants including five previously reported variants (CYP27B1:c.1319_1325dup, p.(Phe443Profs*24), VDR:c.1171C>T, p.(Arg391Cys), PHEX: c.1586_1586+1del, PHEX: c.1482+5G>C, PHEX: c.58C>T, p.(Arg20*)) and six novel variants (CYP27B1:c.974C>T, p.(Thr325Met), CYP27B1: c.1376G>A, p.(Arg459His), CYP2R1: c.595C>T, p.(Arg199*), CYP2R1:c.1330G>C, p.(Gly444Arg),SLC34A3:c.1336-11_1336-1del, SLC2A2: c.589G>C, p.(Val197Leu)) in the genes known to cause monogenic rickets were identified. CONCLUSION: The authors hereby report a case series of individuals from India with a molecular diagnosis of rickets and provide the literature review which would help in enhancing the clinical and molecular profile for rapid and differential diagnosis of rickets.

Smokeless Tobacco Exposure and Fetal Iron Status: An Analytical Study.

Objectives: To compare the cord serum ferritin and fetal iron status in newborns with and without maternal occupational smokeless tobacco exposure and determine the influencing factors. Methods: This cross-sectional study included mother-infant dyads with occupational tobacco exposure (exposed) and an unexposed group. Umbilical cord serum ferritin was compared in both groups. Fetal nicotine absorption was established by cord cotinine. Results: A total of 140 newborns each were analyzed in each group. There was no significant mean difference (MD) (P = 0.900) between the cord serum ferritin in the tobacco exposed and unexposed group. Fetal nicotine absorption was seen in 43.6% of the exposed group. Cord serum ferritin was 14.1 µg/L (95% confidence interval [(95% CI:-43.1, 14.9); P=0.338] lower in this group compared with the group without fetal nicotine absorption. A higher adjusted MD for ferritin was present for maternal hypertension (12.5 [95% CI: -75.5, 100.5]; P = 0.777) and gestational diabetes mellitus (21.4 [95% CI: -54.0, 96.9]; P = 0.571) in the group with fetal nicotine absorption. Fetal nicotine absorption exaggerated fetal iron depletion in maternal anemia [aOR 4.8 (95%CI: 1.2, 19.0); P=0.025]. Conclusion: Cord serum ferritin and fetal iron status were comparable in tobacco exposed and unexposed groups. In those with fetal nicotine absorption, cord ferritin levels reflect the fetal inflammatory state.

Phenotypic and Molecular Heterogeneity in Mandibulofacial Dysostoses: A Case Series From India.

OBJECTIVE: Facial dysostosis is a group of rare craniofacial congenital disabilities requiring multidisciplinary long-term care. This report presents the phenotypic and genotypic information from South India. DESIGN: The study is a case series. SETTING: This was an international collaborative study involving a tertiary craniofacial clinic and medical genetics unit. PATIENTS, PARTICIPANTS: The participants were 9 families with 17 affected individuals of facial dysostosis. INTERVENTION: Exome analysis focused on known genes associated with acrofacial and mandibulofacial syndromes. MAIN OUTCOME MEASURE: The outcome measure was to report phenotyptic and genetic heterogeneity in affected individuals. RESULTS: A Tessier cleft was seen in 7 (41%), lower eyelid coloboma in 12 (65%), ear anomalies in 10 (59%), uniolateral or bilateral aural atresia in 4 (24%), and deafness in 6 (35%). The facial gestalt of Treacher Collins syndrome (TCS) showed extensive phenotypic variations. Pathogenic variants in TCOF1 (Treacher Collins syndrome) were seen in six families, POLR1A (acrofacial dysostosis, Cincinnati type) and EFTUD2 (mandibulofacial dysostosis with microcephaly) in one each. One family (11.1%) had no detectable variation. Five out of six probands with Treacher Collins syndrome had other affected family members (83.3%), including a non-penetrant mother, identified after sequencing. CONCLUSION: Our report illustrates the molecular heterogeneity of mandibulofacial dysostosis in India.

Maternal Occupational Tobacco Exposure and Newborn Umbilical Cord Serum Leptin Concentration.

OBJECTIVE: To assess the effect of maternal occupational tobacco handling (bidi rolling) on cord serum leptin levels. METHODS: We enrolled 64 neonates born to women who were bidi-rollers, and 64 small for gestational age (SGA) neonates and 57 term appropriate for gestational age (AGA) neonates born to mothers with no tobacco exposure. Cord blood leptin levels between the groups were compared. Adjusted mean difference in leptin was calculated using regression model. RESULTS: Cord leptin showed moderate correlation with birthweight (r=0.16; P=0.027) across the groups. Mean (SD) cord serum leptin levels (ng/mL) of study group was 19.79 (13.32), in comparison to 21.4 (13.4) of SGA (P=0.497), and 27.70 (13.96) of term AGA (P=0.002). Maternal occupational tobacco exposure contributed to significant decrease in cord leptin (adjusted mean difference (95%CI): -4.5 ng/mL (-8.82, -0.19); P=0.041). CONCLUSIONS: Maternal occupational tobacco exposure causes signifi-cant reduction in fetal leptin levels.

Maternal and neonatal iodine status in Dakshina Kannada district of Karnataka, India.

This study was designed to assess iodine status of mother-fetus dyad by estimation of spot urine iodine concentration (UIC) in the study district. It is a cross-sectional study of 250 pregnant women with euthyroid status and their term neonates residing in Dakshina Kannada district. Neonates with foetal growth restriction or requiring intensive care were excluded. Median UIC was quantified using modified Sandell-Kolthoff reaction by microplate method. World Health Organization (WHO) classification was used to categorise the iodine status of pregnant women. Among 250 pregnant women, the majority were primigravida (38%). Median maternal thyroid stimulating hormone (TSH) was 1.54 mIU/l, and median UIC was 352 mcg/l. Urine iodine levels were insufficient (<150 mcg/l) in 1.2% (n = 3), adequate (150-249 mcg/l) in 9.2% (n = 23) and above requirement (250-499 mcg/l) in 89.6% (n = 224); none had excess (> 500 mcg/l). Median birth weight was 3,000 g and head circumference was 34 cm. Median cord blood TSH was 8.1 mIU/l, and median UIC 344.5 mcg/l. All the newborns had adequate (> 100 mcg/l) iodine status, including those born to mothers with insufficient values. Maternal and newborn median UIC showed positive correlation (r = 0.139; p = 0.028). Iodine statuses were above requirement or adequate in pregnant women from the study district and their neonates, respectively, indicating successful salt iodisation.

Focal Dermal Hypoplasia with a De novo Mutation p.E300* of PORCN Gene in a Male Infant.

Focal dermal hypoplasia is a rare disorder inherited in an X-linked dominant pattern and is usually antenatally lethal in males. We report a surviving male with postzygotic de novo mutation p.E300* in exon 10 of PORCN gene with mosaicism, earlier reported in a female of Thai origin. This is the first report of this mutation from the Indian subcontinent.

Fatty Acid oxidation disorder with secondary mitochondrial energy production defect: a case report.

The presentation of long-chain fatty acid oxidation disorders (FAOD), unlike short and medium-chain disorders can be with secondary defects in mitochondrial function along with typical features of FAOD. We report an infant with Reye-like presentation and acylcarnitine profile suggestive of very-long-chain acyl-CoA dehydrogenase deficiency who had lactic acidosis and urine gas chromatographic pattern of mitochondrial defects.

Biochemical basis of heterogeneity in acute presentations of propionic acidemia.

Propionic acidemia (PA), an uncommon organic acidemia has varied clinical and metabolic presentation causing difficulty and delay in the diagnosis. We report a case of PA in an infant who presented with failure to thrive, acute encephalopathy due to severe hyperammonemia without acidosis and fungal sepsis. The biochemical basis of severe hyperammonemia is discussed.

Juvenile spondyloarthritis with microscopic colitis.

We report an adolescent girl with long standing spondyloarthritis and chronic diarrhea. Colonoscopy and biopsy revealed microscopic colitis. All serology and HLA-B27 were negative. This case is reported for its rarity and the need to evaluate gut in chronic arthritis to achieve clinical remission.

Mediastinal enteric cyst in a neonate.

Mediastinal enteric cysts are relatively uncommon, and patients tend to present at a later age compared to those with duplications in other areas of alimentary canal. The tendency of enteric cyst to enlarge and produce airway obstruction is sufficient reason for early surgical removal. We report on a case of mediastinal enteric cyst in a neonate with respiratory distress for its early presentation and management. The embryological basis and anatomical issues relating to duplication cysts of the gastrointestinal tract is discussed.

Transient myeloproliferative disorder and eosinophilic pericardial effusion in a down syndrome neonate.

Transient myeloproliferative disorder seen in neonates with Down syndrome is often thought to have a benign course. The authors describe the clinical and laboratory profile of a neonate with Down phenotype and transient myeloproliferative disorder with pericardial effusion as co-morbidity. Pericardial fluid analysis showed eosinophils. Pericardial effusion resolved with prednisolone therapy. Regression in hepatosplenomegaly with clearance of blasts was seen by third week of illness. The clinical course suggested a benign infiltration of the pericardium. Presence of eosinophils supports the differentiating capability of the blast cells in transient myeloproliferative disorders.

SIADH complicating deep neck abscess in infancy.

Symptomatic hyponatremia due to syndrome of inappropriate secretion of anti-diuretic hormone (SIADH) in infancy is seen usually with pneumonia and meningitis and its association with deep neck abscess is not documented. Recognition and appropriate management of this complication is important to prevent mortality and long-term neurological morbidity. We report a 3-month-old infant with parapharyngeal abscess presenting with altered sensorium and recurrent seizures as a result of hyponatremia due to SIADH. The clinical course and outcome is described. Limitation of imaging modalities in an infant with airway compromise is discussed.