Sequencing of exons 1–3 of the VHL gene revealed a novel single base pair substitution (A268C). This replaces asparagine with histidine at codon 90 of VHL (N90H) and was not present in either parent.

Case report A 6-year-old girl was brought into the ED by her parents in the late evening with a 5 week history of colicky, peri-umbilical pain and general malaise. Her mother reported that they had been to the family doctor repeatedly since the onset of symptoms and trialled a number of medications (including antispasmodics and various analgesics) without success. On further questioning, the patient described several episodes of spontaneous vomiting without obvious cause or association over the past month. Her appetite was poor and she had been losing weight. There were no other gastrointestinal or urinary symptoms. There was no history of fever, although she did report ‘sweating for no reason’ on occasion. She had also been suffering from intermittent, generalized headaches without any other focal symptoms over the same time period. She had been previously well, the only noteworthy point in her medical history being her conception through in vitro fertilization. There were no developmental concerns or family history of note. On examination, the patient appeared pale, tired, mildly dehydrated, but apyrexial and comfortable at rest. She was profoundly tachycardic, with a heart rate of 170 beats per minute, and had a BP of 203/157 mmHg on repeat measurements (normal systolic range 90–110 mmHg in this age group). Crucially, as the patient arrived in the early evening, she was triaged in the adult ED and not the paediatric ED (which was closed at this time), where BP would not have been part of routine observations in this age group. Urinary dipstick showed raised protein and blood. General examination was otherwise normal. In discussion with paediatric cardiology, the patient was started immediately on oral nifedipine to control the malignant hypertension prior to further investigation. Blood tests revealed low potassium of 3.0 mmol/L (normal 3.3–4.6) with raised urea (10.0 mmol/L; 2.5–6.5) and creatinine (81 mmol/L; 25–60). Routine haematology and biochemistry bloods (including liver and thyroid function tests) were otherwise unremarkable. An abdominal ultrasound scan demonstrated a 3 × 2.5 cm mass at the upper pole of the left kidney without a distinctly identifiable adrenal gland, a finding confirmed on CT (Fig. 1), which also showed some low attenuation suggestive of cystic change within the mass. Serial urinary metanephrines were subsequently found to be grossly elevated (17.0, 18.1 and 14.7 µmol/mmol creatinine; normal <1.74) with a predominant normetanephrine fraction, suggesting a diagnosis of phaeochromocytoma. Figure 1Open in figure viewerPowerPoint Ultrasound image (above) of the patient's left kidney (between the two crosses) clearly showing an abnormal mass associated with the organ. The adrenal cannot be distinctly identified. The mass was further characterized on CT (below, the mass having been circled). Sympathetic blockade was established first using gradually increasing doses of oral phenoxybenzamine (switched to i.v. dosing in the 5 days prior to surgery), then adding propranolol, aiming for a systolic BP of 80 mmHg with postural drop of 10 mmHg in order to facilitate safe removal of the tumour. Concurrent investigations identified raised serum renin and aldosterone levels consistent with secondary hyperaldosteronism. Serum calcitonin and urinary steroid profiles were normal, as was retinal screening for abnormalities associated with von Hippel-Lindau (vHL) disease, including retinal haemangiomas and hypertensive retinopathy. A laparoscopic left adrenalectomy took place 6 weeks after initial presentation, and priority was placed on close cardiovascular monitoring perioperatively. The patient was fit for discharge 3 days after surgery histology subsequently confirming the diagnosis of phaeochromocytoma.