Agata Vitale

Clinical impact of MEFV mutations in children with periodic fever in a prevalent western European Caucasian population

Objective To evaluate the actual impact of MEFV mutations on clinical manifestations associated with fever attacks in Caucasian children with periodic fever. Methods 113 children carrying MEFV mutations (44 with mutations in two alleles, 69 heterozygous) and 205 children negative for mutations in genes associated with periodic fevers were analysed. The following groups of patients were considered: patients carrying two high penetrance mutations (M694V, M694I, M680I); one high, one low penetrance mutation; two low penetrance mutations; one high penetrance mutation; one low penetrance mutation; genetically negative patients. Results Patients with two MEFV mutations displayed a shorter duration of fever attacks and higher prevalence of a positive family history than patients carrying one MEFV mutation and genetically negative patients. Severe abdominal pain, chest pain and pleurisy were also more frequent in patients with two MEFV mutations compared with children with one MEFV mutation and genetically negative patients. Conversely, a higher frequency of exudative and erythematous pharyngitis, enlargement of cervical lymph nodes, aphthous stomatitis and non-specific skin rash was observed in genetically negative patients and, to a lesser extent, in patients with one MEFV mutation. The frequency of ‘familial Mediterranean fever (FMF)-like symptoms’ decreases from patients carrying two high penetrance mutations towards patients with a single low penetrance mutation with an opposite trend for ‘periodic fever, aphthous stomatitis, pharyngitis, adenitis-like symptoms’. Conclusions This clinical observation supports recent findings contrasting the notion of FMF being a pure autosomal recessive disorder associated with recurrence of mutations leading to loss of protein function. A dosage effect could be invoked, giving rise to symptom onset even in the presence of one wild-type allele.

Arthritis and gum bleeding in two children.

In developed countries, scurvey is quite rare and can be seen in children with severely restricted diets, related to psychiatric or developmental problems. Clinical presentation can include arthralgias/arthritis, myalgias, hemarthrosis, purpura and ecchymosis.

Vitamin D intoxication in two brothers: be careful with dietary supplements

Abstract Vitamin D (VitD) intoxication, a well-known cause of hypercalcaemia in children, has renal, cardiac and neurological consequences. Iatrogenic or accidental administrations are the most common causes. We present two cases of hypervitaminosis D due to over-the-counter VitD supplement self-medication. A 12-year-old boy was hospitalised for abdominal pain, constipation and vomiting. Routine biochemistry indicated severe hypercalcaemia and renal failure. Plasma 25-OH VitD level was very high and parathyroid hormone was suppressed. Renal ultrasound showed nephrolithiasis. Hydration, diuretics and prednisone induced a progressive reduction of calcium levels. His brother, who was receiving the same treatment, was hospitalised although asymptomatic. Normal serum calcium and renal function were revealed, while 25-OH VitD was high and parathyroid hormone was suppressed. Renal ultrasound was within the normal range. Examination of the VitD content of the over-the-counter supplement revealed a higher amount than declared. VitD administration implies several risks and must be prescribed only when needed and under strict medical control.

Hypokalaemia and failure to thrive: Report of a misleading onset

Aim:  We report a case of Gitelman Syndrome (GS) in a 9‐year‐old girl, previously diagnosed as a Bartter syndrome at one year of life.

A riddle for paediatricians: Two siblings with recurrent urticaria and fever

Patient 1 is the first son of non-consanguineous parents of Caucasian origin. At 12 weeks of age, after the first vaccination, he developed fever, erythematous rash on the trunk and lower limbs, and diarrhea, which lasted for 5 days, with spontaneous resolution. Since then, he had experienced recurrent and selflimited febrile attacks accompanied by a diffuse pruritic maculopapular rash (Fig. 1), abdominal pain, watery stools, cervical lymphadenopathy, headache with significant elevation in the acute-phase reactants. Attacks occurred every 4–6 weeks, lasting for 4–7 days, and were interrupted by asymptomatic intervals. At the age of 5 years, he was referred to our Unit with ongoing episodes of periodic fever associated with abdominal pain, vomiting and a macular pruritic rash. Extensive investigations revealed erythrocyte sedimentation rate 90 mm/h (Westergreen, normal value (n.v.) < 16 mmh), C-Reactive protein 60 mg/L (n.v. 5 mg/L), white blood cells 15.00 ¥ 10/L with 82% of neutrophils, haemoglobin 10.9 g/dL, platelet count 546 ¥ 10/L, Serum Amyloid A (SAA) 90 mg/L (n.v. 0–10) at the time of fever. Serum immunoglobulins, including immunoglobulin D (IgD) and immunoglobulin A (IgA), were in the normal range for age: IgD 25 IU/mL (n.v. 0–40), IgA 152 mg/dL (n.v. 14–159). Additional investigations were non-contributory. An autoinflammatory syndrome was suspected. DNA analysis of genes associated with TNF receptor associated periodic syndrome (TNFRSF1A), cryopyrin associated periodic syndrome (CIAS1) and familial Mediterranean fever were normal. The patient was confirmed to have hyper-immunoglobulin D syndrome (HIDS) with mutation of the mevalonate kinase (MVK) gene (compound heterozygote I268D, 3137W). Colchicine was commenced, resulting initially in the reduction of the duration of attacks. Whilst on colchicine, the child has not had any further attacks for the last 2 years and SAA has normalised.

A 14-year-old girl with a sudden arm swelling after axillary depilatory wax.

Takayasu’s arteritis is a systemic vasculitis predominantly affecting the aorta and its major branches. We report a 14-year-old girl in whom incidentally a deep upper limb vein thrombosis was found. She was referred to the emergency unit due to swelling and intermittent cyanosis of the right arm following an axillary depilatory wax. High-resolution echo colour Doppler ultrasonography showed a deep vein thrombosis with thickening of the proximal common carotids. A diagnosis of type IIb Takayasu’s arteritis was made. The patient’s history revealed fatigue, myalgia and headache. Immunosuppressive treatment and anticoagulation were introduced with a rapid and sustained improvement.