We describe a case series of five infants (age range: 1–90 days; 4 females and 1 male) who presented to Al Jalila Children’s intensive care units (ICU) with complex multisystem disorders. Patients were Emirati, Kenyan, Jordanian, Filipino, or Pakistani. Trio rapid whole genome sequencing (rWGS) was performed on all five patients and their parents within the hospital’s genomics facility. Results were returned within ~37 h from blood sample draws and were diagnostic in 3 out of 5 patients. Positive findings were a homozygous pathogenic variant in POMT1 gene causing muscular dystrophydystroglycanopathy, a mosaic tetrasomy of the short arm of chromosome 12 (12p13.33p11.1) causing Pallister-Killian syndrome, and compound heterozygous pathogenic variants in the LIPA gene causing lysosomal acid lipase deficiency and Wolman disease. The rWGS analysis provided fast and precise diagnostic findings in those 3 patients and also aided in devising better management plans for them in the intensive care setting. For example, the 3-month-old infant with pathogenic variants in the LIPA gene is now a candidate for an FDA-approved, potentially lifesaving enzyme replacement therapy (sebelipase alfa). Our case series emphasize the feasibility and utility of rWGS in pediatric intensive care setting, in a diverse population that has long been underserved in genomic services. Significant investments in local healthcare infrastructure are needed, globally, for more equitable access of genomic medicine among vulnerable patients.
Key Points Question What are the clinical, genetic, and laboratory characteristics of Middle Eastern patients with multisystem inflammatory syndrome in children (MIS-C)? Findings In this cohort study of 45 patients with MIS-C of primarily Arab and Asian origins, an enrichment of rare, likely deleterious immune-related genetic variants was found, with a possible association between genetic findings and MIS-C onset and resistance to treatment. Meaning These findings suggest that comprehensive genetic profiling of patients with MIS-C of diverse ethnicities is essential to characterize the genetic contribution to this disease.
We studied 19 infants with a mean age of 3.8 months who presented with features consistent with acute lead encephalopathy following the use of traditional medicines. All presented with convulsions; CT scans of the brain on admission showed brain oedema in four, atrophy in four and normal findings in 11. Cerebrospinal fluid analysis in nine patients showed pleocytosis in six and a high protein content in eight. The median lead level in these 19 infants which encephalopathy was 3.6 mumol/l (74.5 micrograms/dl). Seven had a mean lead level of only 2.7 mumol/l (56.9 micrograms/dl) which is much below 70 micrograms/dl, the level usually proposed as the threshold for encephalopathy. Thirteen infants developed brain damage during follow-up; statistical analysis correlated the lead level at 2 months post chelation with an abnormal neurological outcome. Our findings indicate that in very young infants acute lead encephalopathy may occur at lead level lower than previously reported.
Six infants, three of them neonates, were diagnosed as having acute lead poisoning; four of them had acute encephalopathy. All had been given an indigenous preparation, 'Bint Al Zahab' (Daughter of Gold), for abdominal colic and early passage of meconium after birth. Chemical analysis of this powder revealed a lead content of 82.5%. The index case had anaemia with punctate basophilia, dense metaphysial lines on X-ray and markedly raised blood lead levels, arousing a strong index of suspicion for the early diagnosis of subsequent cases. Computerized axial tomography (CAT) scan in three cases showed signs of early cerebral cortical atrophy. The picture of cerebral oedema was absent in the four cases of acute lead encephalopathy. The importance of prevention and the ideal management is discussed.
Studies of genetic factors associated with severe COVID-19 in young adults have been limited in non-Caucasian populations. Here, we use whole exome sequencing to characterize the genetic landscape of severe COVID-19 in a well phenotyped cohort of otherwise healthy, young adults (N=55; mean age 34.1 ± SD 5.0 years) representing 16 countries in Asia, the Middle East, and North Africa. Our findings show enrichment of rare, likely deleterious missense and truncating variants in interferon-mediated and bacterial infection-susceptibility genes, when compared to control, mildly affected, or asymptomatic COVID-19 patients (N = 25), or to general populations representing Asia and the Middle East. Genetic variants tended to associate with mortality, intensive care admission, and ventilation support. Our findings confirm the association of interferon pathway genes with severe COVID-19 and highlight the importance of extending genetic studies to diverse populations given implications for pan-ethnic therapeutic and genetic screening options.
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