Craniosynostosis With Preoperative Iron Supplementation Exposure: A Retrospective Cohort Study Examining Preoperative Iron Supplementation and Transfusion Practice in a National Paediatric Craniofacial Centre.

BACKGROUND: Blood loss and subsequent transfusion are key concerns in the surgical management of craniosynostosis, and have been associated with increased morbidity, requirement for intensive care admission and increased length of hospital stay. Patient blood management guidelines advocate treatment of anemia before elective surgical procedures where significant blood loss is anticipated. At present there is little evidence in the literature investigating the clinical value of this practice in pediatric craniofacial surgery. AIMS: The authors examined the effect of preoperative oral iron supplementation on blood loss and transfusion rates in a national pediatric craniofacial unit. METHODS: A total of 157 patients were included in a retrospective and prospective observational cohort study conducted between July 2011 and November 2016. Eighty-five (85) patients included in the preoperative iron supplementation group were prescribed oral ferrous fumarate before total cranial vault reconstruction, frontal-orbital advancement or extended strip cranial vault remodeling procedures. This cohort was retrospectively compared to seventy-two (72) consecutive patients who did not receive iron supplementation. RESULTS: Calculated blood loss was 51.3 mL/kg in the intervention group, and 56.65 mL/kg in the control group. Transfusion rate and mean volumes for the intervention group were 85.9% and 25 mL/kg. The control group had transfusion rate of 86.1% with mean transfused volume of 24.7 mL/kg. These differences were not statistically significant. Intraoperative tranexamic acid was associated with significantly reduced transfusion volumes overall. CONCLUSIONS: This study did not show a statistically significant benefit to preoperative iron supplementation. Secondary outcomes of this study showed a statistically significant difference in estimated versus calculated intraoperative blood loss. Further research in to specific iron supplementation protocols is indicated.

Hypoglycemia is not a defining feature of metabolic crisis in mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase deficiency: Further evidence of specific biochemical markers which may aid diagnosis.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA (HMG Co-A) synthase (mHS) deficiency is an autosomal recessive disorder of ketone body synthesis which has traditionally been associated with hypoketotic hypoglycemia, hepatomegaly and encephalopathy, presenting in early childhood following a period of fasting. We report the third case of mHS deficiency presenting in the absence of hypoglycemia, with profound biochemical abnormalities and further evidence of potential specific diagnostic biomarkers. A previously well, 20-month old, unvaccinated male, of nonconsanguineous Polish heritage, presented with encephalopathy, hepatomegaly, severe metabolic acidosis, and mild hyperammonemia following a brief intercurrent illness. The patient was reported to have taken colloidal silver prior to presentation, posing a further diagnostic challenge. Additionally, he developed features suggestive of hemophagocytic lymphohistiocytosis during treatment. While the patient was normoglycemic prior to dextrose administration, the sample was markedly lipemic, with significant hypertriglyceridemia detected. Urine organic acid analysis revealed dicarboxylic aciduria with 4-hydroxy-6-methyl-2-pyrone (4HMP) and the presence of three other previously reported putative biomarkers for mHS deficiency. Glutarate was markedly elevated in the initial chromatogram, with a mild increase in 3-hydroxyglutarate (3HG) persisting. Raised acetylcarnitine was detected on acylcarnitine profile. Molecular genetic analysis of the HMGCS2 gene identified compound heterozygosity for known pathogenic mutations c.634G>A and c.1016+1G>A, confirming the diagnosis of mHS deficiency. This case provides further evidence that hypoglycemia is not invariably present in symptomatic mHS deficiency. We propose that elevated acetylcarnitine, triglycerides, and 3HG are additional biochemical features during acute presentations. With the expansion of novel biomarkers, further cases of this rare disorder may emerge.