ABSTRACT
OBJECTIVE: To assess the incidence and predictors of splenic dysfunction in children with sickle cell disease (SCD). METHODS: A cross-sectional study was conducted between June 2019 and December 2020 where children aged 1 to 15 years of age with SCD were screened for splenic dysfunction. Children who were splenectomised, those with other diseases known to affect splenic function like congenital malformations, immunodeficiencies, and chronic diseases like tuberculosis, nephrotic syndrome, diabetes mellitus, chronic liver disease, celiac disease or malignancy were excluded. Splenic size was assessed by clinical examination and ultrasonography. Splenic dysfunction was assessed using splenic scintigraphy using Technetium-99m (99mTc) labeled autologous RBCs and by the presence of Howell Jolly bodies in the peripheral smear. Laboratory and clinical predictors of splenic dysfunction were assessed by multiple logistic regression. RESULTS: We evaluated 66 children with SCD with a mean (SD) age of 7.41 (3.3) years. Impaired and absent splenic function as assessed by 99mTc scintigraphy was found in 13 (19.7%), and 3 (4.6%) children, respectively. Howell Jolly bodies in peripheral smear were found in 5 (7.5%) children; 3 of them had abnormal uptake on scintigraphy; all five had splenomegaly. Age > 5 years, > 4 episodes of vaso-occlusive crisis (VOC), > 3 hospitalization events in the past, > 5 blood transfusions, children not receiving hydroxyurea, reticulocyte count > 4%, and HbS > 70% were independent predictors of splenic dysfunction. CONCLUSION: The prevalence of splenic dysfunction in children with SCD in Central India is lower than that reported from the West. The decision to start antibiotic prophylaxis can be individualized in these children.
ABSTRACT
Glutaric aciduria type II, also known as Multiple acyl-CoA Dehydrogenase Deficiency, results from a defect in the mitochondrial electron transport chain resulting in an inability to break down fatty-acids and amino acids. There are three phenotypes- type 1 and 2 are of neonatal onset and severe form, with and without congenital anomalies, respectively, and presents with acidosis, severe hypotonia, cardiomyopathy, hepatomegaly, and non-ketotic hypoglycemia. Type 3 or late-onset Multiple acyl-CoA Dehydrogenase Deficiency usually presents in the adolescent or adult age group with phenotype ranging from mild forms of myopathy and exercise intolerance to severe forms of acute metabolic decompensation on its chronic course. Type 3 Multiple acyl-CoA Dehydrogenase Deficiency rarely presents in infancy and in liver failure. We present a five-month-old developmentally normal female child with acute encephalopathy, hypotonia, non-ketotic hypoglycemia, metabolic acidosis, and liver failure, with a history of sibling death of suspected inborn error of metabolism. The blood acyl-carnitine levels in Tandem Mass Spectrometry and urinary organic acid analysis through Gas Chromatography-Mass Spectrometry were unremarkable. The patient initially responded to riboflavin, CoQ, and supportive management but ultimately succumbed to sepsis with shock and multi-organ dysfunction. The clinical exome sequencing reported a homozygous missense variation in exon 11 of the ETFDH gene (chr4:g.158706270C > T) that resulted in the amino acid substitution of Leucine for Proline at codon 456 (p.Pro456Leu) suggestive of Glutaric aciduria type IIc (OMIM#231,680).
