Recessive Mutations in NDUFA2 Cause Mitochondrial Leukoencephalopathy

Deficiencies of mitochondrial respiratory chain complex I frequently result in leukoencephalopathy in young patients, and different mutations in the genes encoding its subunits are still being uncovered. We report two patients with cystic leukoencephalopathy and complex I deficiency with recessive mutations in NDUFA2, an accessory subunit of complex I. The first patient was initially diagnosed with a primary systemic carnitine deficiency associated with a homozygous variant in SLC22A5, but also exhibited developmental regression and cystic leukoencephalopathy, and an additional diagnosis of complex I deficiency was suspected. Biochemical analysis confirmed a complex I deficiency, and whole exome sequencing revealed a homozygous mutation in NDUFA2 (c.134A>C, p.Lys45Thr). Review of a biorepository of patients with unsolved genetic leukoencephalopathies who underwent whole exome or genome sequencing allowed us to identify a second patient with compound heterozygous mutations in NDUFA2 (c.134A>C, p.Lys45Thr; c.225del, p.Asn76Metfs*4). Only one other patient with mutations in NDUFA2 and a different phenotype (Leigh syndrome) has previously been reported. This is the first report of cystic leukoencephalopathy caused by mutations in NDUFA2.

Graphical abstract

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Dural ectasia associated with Mounier-Kuhn syndrome: a novel association in the context of spinal stenosis

We present the case of a patient undergoing lumbar spine decompression for stenosis with a history of Mounier-Kuhn syndrome. The patient presented with axial lumbar spine pain over 6 months with progressive radicular pain to the left L3 dermatome. MRI confirmed spinal stenosis at L3/4 level with associated dural ectasia. The patient had an uneventful spinal decompression with resolution of radicular symptoms and axial spine pain. Dural ectasia poses a significant risk when operating on the lumbosacral spine. Larger cerebrospinal fluid volumes and a capacious dural canal can result in anaesthetic and orthopaedic complications such as inadequate spinal anaesthesia, complicated epidural analgesia, intraoperative dural tears and difficult pedicle screw insertion due to narrow pedicles. This is the first case in the literature detailing the association between dural ectasia and Mounier-Kuhn syndrome. We recommend adequate spinal imaging in patients with Mounier-Kuhn syndrome to exclude dural ectasia prior to undergoing lumbosacral spinal procedures.

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Decreased severity of Shiga toxin-producing Escherichia coli haemolytic uraemic syndrome (STEC-HUS) in a child with type 1 von Willebrand disease

Shiga toxin-producing Escherichia coli-associated haemolytic uraemic syndrome (STEC-HUS) is characterised by haemolytic anaemia, thrombocytopenia and acute kidney injury. Von Willebrand Factor (vWF) is an important mediator of normal thrombi formation and indirect evidence suggests that vWF may play an important role in Shiga toxin-induced thrombi formation. Clinical evidence supporting the role of vWF in STEC-HUS is lacking. A 10-year-old girl with type 1 von Willebrand Disease (vWD) had a mild case of STEC-HUS, with nadir haemoglobin 7.3 g/dL and platelet count 105x10⁹ cells/L and peak serum creatinine 0.56 mg/L and lactate dehydrogenase 741 U/L. This is the first report of STEC-HUS in a patient with vWD. We speculate that the quantitative deficiency of vWF associated with type 1 vWD may have attenuated the course of disease by reducing platelet aggregation, complement activation and thrombi formation. This case adds to a growing literature supporting a link between vWF and STEC-HUS.

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Primary mediastinal seminoma presenting with superior vena caval obstruction

Description

A previously well 29-year-old man presented with a 2-week history of progressive orthopnoea, dry cough, neck and facial swelling, and night sweats. On further questioning, he described 2 kg of weight loss and increasing swallowing difficulties over the previous year. An oesophagogastroduodenoscopy performed 1 year prior was unremarkable. A chest radiograph demonstrated a large mediastinal mass (figure 1A), and a subsequent CT scan revealed a large anterior mediastinal mass measuring 11 cm in diameter. There was central necrosis and complete occlusion of the superior vena cava (SVC; figure 1C,D). An urgent biopsy of the mass was performed, and immunohistochemistry showed malignant cells positive for OCT3/4, placental alkaline phosphatase, D2-40 and CD117 but negative for pancytokeratin, S100, CD30, human chorionic gonadotropin (HCG), alpha-foetoprotein (AFP), CD45, CD20 and CD3. There were no masses found elsewhere on CT imaging of the chest, abdomen, pelvis and head, or on testicular ultrasonography....

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Duplex gall bladder: bystander or culprit

Gall bladder (GB) duplication is a rare anatomical malformation, which can be detected by preoperative imaging study. We present a case of duplex gall bladder in a 14-year-old boy who presented with abdominal pain. On ultrasound, he had right nephrolithiasis and duplex gall bladder. Duplex gall bladder was confirmed on MR cholangiopancreatography. There was a dilemma for surgical management of duplex gall bladder; however, he became asymptomatic after conservative treatment. Prophylactic surgery is not recommended for asymptomatic incidentally detected duplex gall bladder. Radiologists and paediatric surgeons should be sensitised about the exact anatomy of this entity.

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Acute rhabdomyolysis and delayed pericardial effusion in an Italian patient with Ebola virus disease: a case report

During the 2013–2016 West Africa Ebola virus disease (EVD) epidemic, some EVD patients, mostly health care workers, were evacuated to Europe and the USA.

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Neonatal outcomes following exposure in utero to fallout from Chernobyl

Abstract

Iodine 131 (I-131), the principal component of nuclear fallout from the Chernobyl accident, concentrates in the thyroid gland and may pose risks to fetal development. To evaluate this, neonatal outcomes following the accident in April of 1986 were investigated in a cohort of 2582 in utero-exposed individuals from northern Ukraine for whom estimates of fetal thyroid I-131 dose were available. We carried out a retrospective review of cohort members' prenatal, delivery and newborn records. The relationships of dose with neonatal anthropometrics and gestational length were modeled via linear regression with adjustment for potentially confounding variables. We found similar, statistically significant dose-dependent reductions in both head circumference (−1.0 cm/Gy, P = 0.005) and chest circumference (−0.9 cm/Gy, P = 0.023), as well as a similar but non-significant reduction in neonatal length (−0.6 cm/Gy, P = 0.169). Gestational length was significantly increased with increasing fetal dose (0.5 wks/Gy, P = 0.007). There was no significant (P > 0.1) effect of fetal dose on birth weight. The observed associations of radioiodine exposure with decreased head and chest circumference are consistent with those observed in the Japanese in utero-exposed atomic bomb survivors.

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