Helena Pinto

A novel splicing mutation causes analbuminemia in a Portuguese boy

Analbuminemia is a rare autosomal recessive disorder manifested by the absence or severe reduction of circulating serum albumin in homozygous or compound heterozygous subjects. It is an allelic heterogeneous defect, caused by a variety of mutations within the albumin gene. The analbuminemic condition was suspected in a Portuguese boy who presented with low albumin level (about 3.8 g/L) and a significant hypercholesterolemia, but with no clinical findings. The albumin gene was screened by single strand conformational polymorphism and heteroduplex analysis and submitted to direct DNA sequencing. The proband was found to be homozygous for a previously unreported G>A change at position c.1289+1, the first base of intron 10, which inactivates the strongly conserved GT dinucleotide at the 5 splice site consensus sequence of the intron. The effect of this mutation was evaluated by examining the cDNA obtained by RT-PCR from the albumin mRNA extracted from probands leukocytes. The splicing defect results in the skipping of the preceding exon. The subsequent reading frame-shift in exon 11 produces a premature stop codon located 33 codons downstream the 5 end of the exon. This extensive cDNA alteration is responsible for the analbuminemic trait. Both parents were found to be heterozygous for the same mutation. DNA and cDNA sequence analysis established the diagnosis of congenital analbuminemia in the proband. The effects of the so far identified splice-site mutations in the albumin gene are discussed.

Deveremos avaliar a pressão arterial no recém‐nascido?

Dilated cardiomyopathy is the most common form of cardiomyopathy and the main cause of cardiac transplantation in children and in adults. Infants and children have a wider spectrum of etiologies, hampering their identification. The most frequent initial manifestation of dilated cardiomyopathy is symptomatic heart failure during exercise or at rest (although many patients are asymptomatic). Some causes are potentially reversible, therefore the investigation should be carefully planned and immediately performed after diagnosis. In most children no cause is identified, which limits the targeted therapeutic approach and therefore the effectiveness of the treatment. The authors present a case of dilated cardiomyopathy secondary to renovascular hypertension diagnosed in an infant with 3.5 month-old, highlighting the etiological investigation, treatment and evolution. The authors present this case emphasising the fact that the arterial hypertension diagnose in infants is not always easy, questioning the current recommendations relating to an initial evaluation on blood pressure. We postulate that the assessment of blood pressure in newborns can detect early renovascular hypertension (and even other cardiovascular diseases) and help prevent the development of deleterious effects, including fatal episodes.

Hyponatremic hypertensive syndrome secondary to renal ischemia – Case report

Hyponatremic hypertensive syndrome (HHS) is characterized by hypertensive crisis, and hyponatremia secondary to unilateral renal damage with glomerular and tubular dysfunction. Elevated plasma levels of renin in most cases suggest that the stimulation of renin release from the ischemic kidney plays an important pathophysiologic role. Activation of the renin-angiotensin system results in hypertension and causes secondary hyperfiltration, pressure diuresis and sodium loss from contralateral non-damaged kidney. An elevated renin level is a pathognomonic finding in HHS. Potassium deficiency from hyperaldosteronism may further stimulate renin secretion and intensify this vicious circle. We report a female term newborn, who presented with hypertensive crisis on the seventh day after traumatic birth. The first three days of life were uneventful. Initial treatment with captopril resulted in severe hypotension and hemodynamic instability. Lab work revealed hyponatremia, hypokalemia, and elevated peripheral renin activity and aldosterone levels. Complementary sonography and magnetic resonance confirmed right adrenal gland hematoma and several ischemic areas in the upper pole of the right kidney. The diagnosis of HHS secondary to renal ischemia was evoked. HHS is a rare condition in the neonatal period, though still under-recognized. In the neonatal and early infancy period, renovascular disease is the most common cause of secondary hypertension. In this case, there was no sign of vascular disease, the renin-angiotensin system was activated secondary to direct renal ischemia and infarction. The intense renin stimulation and pressure through the contralateral normal kidney results in high pressure natriuresis facilitating a severe volume-depleted state. Although the use of renin-angiotensin system inhibitors is the treatment of choice, it is imperative to re-establish hydration and renal perfusion before starting this antihypertensive medication. We aimed to improve awareness of HHS diagnosis and prompt treatment, to prevent continuous renal damage and other life-threatening complications.

Wave of renal impairment

We present a case of a 51-year-old man who went to the emergency department after an almost-drowning episode, presenting with muscular weakness, myalgia and dark urine. Laboratory data showed a severe rhabdomyolysis (creatine kinase 497u2009510u2009U/L). Despite aggressive fluid therapy, an oliguric acute kidney injury was established with temporary need of haemodialysis. The patient had a longtime history of exercise intolerance and family history of a metabolic myopathy, namely a sister with McArdle’s disease. The genetic test was positive. McArdle’s disease is an autosomal recessive disorder caused by mutations in the muscle glycogen phosphorylase gene that encodes the myophosphorylase. The main symptom consists in exercise intolerance and the most severe complication is rhabdomyolysis with acute renal failure. Metabolic myopathies, such as McArdle’s disease, should be considered in patients with acute renal failure due to unexplained severe rhabdomyolysis, especially if there are chronic complaints of exercise intolerance and positive family history.

Proliferative glomerulonephritis with linear immunoglobulin deposition: is this atypical antiglomerular basement membrane disease?

The antiglomerular basement membrane (anti-GBM) antibody disease is marked by the presence of specific antibodies against the non-collagenous domain of the type IV collagen’s α3 chain. We describe a case of a 24-year-old Caucasian man, who may have had an atypical presentation of anti-GBM (slow progressive renal insufficiency, massive proteinuria and no detectable circulating anti-GBM antibody). The patient was treated with steroids and cyclophosphamide. This approach failed to attenuate the disease, and so rituximab was initiated with subsequent clinical improvement, normalisation of urinary sediment and marked regression of proteinuria; renal function remained stable. The renal biopsy immunofluorescence was crucial for the diagnosis.

Minimal change disease with maximum immunosuppression: successful treatment of steroid-dependent minimal change disease with rituximab

Minimal change disease (MCD) is usually steroid sensitive, although in case of steroid dependent and multiple relapses we can struggle with different immunosuppressive agents, sometimes with no response. Rituximab has been emerging as an alternative therapeutic option. We describe a case of a young patient with MCD that had frequent relapses and steroid dependency, with no response to several immunosuppressive agents during 15 years of disease. He was kept under high-dose steroids and ciclosporin. He started treatment with rituximab (two administrations of 1u2009g 2 weeks apart, repeating after 6 months). The steroids dose was gradually reduced and the ciclosporin was stopped. During the entire 2 years follow-up period, he remained in remission and had no adverse events. This remarkable outcome reinforces the option of using rituximab in difficult cases, allowing the reduction of steroid burden and its adverse effects, which is of extreme importance, especially in young patients.

A interculturalidade em Educação Patrimonial: desafios e contributos para o ensino de História

No ensino de Historia, aspectos curriculares interdisciplinares relacionados com o uso do patrimonio cultural ou a problematizacao em torno do desenvolvimento de atitudes de tolerância, de respeito pela diferenca e cooperacao entre povos, necessitam de uma reflexao fundamentada e sistematica sobre concepcoes de alunos e professores em areas centrais para a Educacao Historica, como a da interculturalidade. Com o objetivo de aprofundar, numa abordagem essencialmente qualitativa, a compreensao dos sentidos atribuidos por alunos e professores a fontes patrimoniais, em articulacao com conceitos ligados a consciencia historica, nomeadamente os de identidade e de patrimonio, analisaram-se as concepcoes de alunos de 7.o ano e de 10.o ano de varias escolas do norte de Portugal, acerca da forma como interpretam fontes patrimoniais e, ainda, como os seus professores entendem o uso de fontes patrimoniais no ensino e aprendizagem de Historia, dada a sua relacao com a interpretacao como processo de construcao de significado acerca do passado. Neste estudo registaram-se diferentes perfis de identidade consoante o padrao de pensamento, desde uma identidade local/nacional fundada nas origens, i.e. exclusiva, ate uma identidade mais inclusiva e europeia/global. Os resultados do estudo permitem abrir possibilidades de novas formas de abordagem educativa relacionadas com a utilizacao do patrimonio como evidencia historica, contribuindo para o desenvolvimento da consciencia historica e patrimonial.