STT3A‐CDG (OMIM# 615596) is an autosomal recessive N‐linked glycosylation disorder characterized by seizures, developmental delay, intellectual disability, and a type I carbohydrate deficient transferrin pattern. All previously reported cases (n = 6) have been attributed to a homozygous pathogenic missense variant c.1877C>T (p.Val626Ala) in STT3A. We describe a patient with a novel homozygous likely pathogenic missense variant c.1079A>C (p.Tyr360Ser) who presents with chronically low Factor VIII (FVIII) and von Willebrand Factor (vWF) levels and activities in addition to the previously reported symptoms of developmental delay and seizures. VWF in our patient's plasma is present in a mildly hypoglycosylated form. FVIII antigen levels were too low to quantify in our patient. Functional studies with STT3A−/− HEK293 cells showed severely reduced FVIII antigen and activity levels in conditioned media <10% expected, but normal intracellular levels. We also show decreased glycosylation of STT3A‐specific acceptors in fibroblasts from our patient, providing a mechanistic explanation for how STT3A deficiency leads to a severe defect in FVIII secretion. Our results suggest that certain STT3A‐dependent N‐glycans are required for efficient FVIII secretion, and the decreased FVIII level in our patient is a combined effect of both severely impaired FVIII secretion and lower plasma VWF level. Our report expands both the genotype and phenotype of STT3A‐CDG; demonstrating, as in most types of CDG, that there are multiple disease‐causing variants in STT3A.

ObjectiveShort, early childhood falls rarely cause severe brain injuries or death. However, it is important to recognize that they occasionally occur because of unusual circumstances. We sought to document several such injuries.MethodsRecords and imaging were reviewed for children younger than 6 years, hospitalized between 2015 and 2020 for major closed head injuries following less than 4-ft falls. Major injury was defined as intensive care admission more than 2 days, neurosurgical intervention, death, or disability at hospital discharge. Subjects were identified through Seattle and Spokane, Washington abuse consultations. Harborview Medical Center's trauma registry and Seattle Children's Hospital's Hemophilia Treatment Program and Radiology were searched for subjects.ResultsWe identified 12 young children who sustained major closed head injury due to short falls. Seven developed major space-occupying epidural hemorrhages. One child developed internal hydrocephalus after intraventricular hemorrhage. One child with prior meningomyelocele, Chiari 2 malformation, and ventriculoperitoneal shunt developed shunt decompensation after an acute-on-chronic subdural hemorrhage. One child developed an internal capsule stroke because of a previously undiagnosed calcifying angiopathy. Another child developed space-occupying subdural hemorrhage associated with previously unrecognized platelet pool disorder. Only this child had abuse concerns, which were resolved with his coagulopathy diagnosis. One child had a diastatic skull fracture leading to pseudomeningocele.At Harborview Medical Center, 140 children were seen for short falls in the emergency department or inpatient service. Among the 40 needing intensive care, 4 (12.5%) had major injuries after short falls. Our hemophilia treatment program did not see any children who had sustained major injury following a short fall in a 5½ year period.ConclusionsAlthough young children rarely sustain major head injury following short falls, serious head injuries do occasionally occur because of unusual injury mechanisms or preexisting conditions. It is important to fully evaluate these patients to differentiate these unintentional falls from abusive head injury.

Hemophilia A is characterized by deficiency of factor VIII. We present a unique, illustrative case of an infant with a short history of neck pain and irritability without neurological deficits who was found to have a spinal epidural hematoma. The subsequent investigation for the etiology, including workup for nonaccidental trauma, led to a diagnosis of severe hemophilia A.