ABSTRACT Primary hyperoxaluria type 1 is a rare genetic disease caused by mutations in AGXT, leading to an excessive hepatic production of oxalate, resulting in urolithiasis, nephrocalcinosis and chronic kidney disease. The authors present the case of a young female with PH1 who is the first patient treated with lumasiran in Portugal, and currently has a follow-up of 18 months.

ABSTRACT Hemolytic uremic syndrome (HUS) triggered by influenza virus (iHUS) is rare. Influenza A infections have been described to trigger atypical HUS (aHUS) in individuals with an underlying genetic complement dysregulation. To date there are only few reports of Influenza B as a trigger of aHUS, all identified cases associated with mutations in the MCP or C3 gene, occasionally combined with other mutations. aHUS patients should be screened for all known disease-associated genes and screening should not be stopped after finding a mutation, to identify other genetic susceptibility factors influencing gene phenotype, particularly in patients with MCP or CFI mutations. Complement blockade using a monoclonal anti-C5 antibody, eculizumab, has greatly improved the outcome in recent years for certain groups of HUS. The decision on whether to treat or not with eculizumab should be made based on clinical and laboratorial evolution as well as molecular studies results. Influenza A and B are preventable through vaccination and strategies should be addressed for patients with complemente gene mutations identified.

Resumo O raquitismo fosfopênico pode ser causado por mutações no gene PHEX (ligado ao X do homólogo da endopeptidase que regula o fosfato). Atualmente, mais de 500 mutações no gene PHEX causam raquitismo hipofosfatêmico. Os autores relatam um caso clínico de uma menina de 4 anos com histórico familiar sem relevância, que apresentou falha no crescimento e arqueamento das pernas. Os exames laboratoriais mostraram hipofosfatemia, fosfatase alcalina elevada, cálcio normal, PTH levemente elevado e níveis normais de 25(OH)D e 1,25(OH)D. O estudo radiológico mostrou deformidades ósseas no rádio e no fêmur. O diagnóstico clínico do raquitismo fosfopênico foi realizado e o estudo genético detectou uma provável variante patogênica heterozigótica do gene PHEX: c.767_768del (p.Thr256Serfs*7). Esta variante não foi descrita anteriormente na literatura ou nas bases de dados. O conhecimento sobre novas mutações pode melhorar o desfecho de pacientes. A análise genética pode ajudar a estabelecer uma correlação genótipo-fenótipo.

Abstract Phosphopenic rickets may be caused by mutations in the PHEX gene (phosphate regulating endopeptidase homolog X-linked). Presently, more than 500 mutations in the PHEX gene have been found to cause hypophosphatemic rickets. The authors report a clinical case of a 4-year-old girl with unremarkable family history, who presented with failure to thrive and bowing of the legs. Laboratory tests showed hypophosphatemia, elevated alkaline phosphatase, normal calcium, mildly elevated PTH and normal levels of 25(OH)D and 1.25(OH)D. The radiological study showed bone deformities of the radius and femur. Clinical diagnosis of phosphopenic rickets was made and the genetic study detected a heterozygous likely pathogenic variant of the PHEX gene: c.767_768del (p.Thr256Serfs*7). This variant was not previously described in the literature or databases. Knowledge about new mutations can improve patient’s outcome. Genetic analysis can help to establish a genotype-phenotype correlation.

Background: Primary hyperoxaluria type 1 is a rare autosomal recessive inherited disease, caused by mutations in AGXT gene, with an estimated incidence of 1:100.000 live births per year in Europe. Over 50% present with end stage renal disease at diagnosis. Case reports: The first case is a 14-year-old boy, second child to consanguineous parents, with history of recurrent lithiasis and ureteral dilatation starting 5 years before. Urine/stone analysis revealed calcium oxalate monohydrate crystals and markedly elevated urine oxalate excretion. Genetic tests confirmed a mutation in AGXT gene, c.1151T>C, in homozygosity. Two years after, nephrocalcinosis was identified and glomerular filtration rate gradually declined. Oxalate deposition in solid organs was excluded and successful orthotopic liver transplantation was performed, with stabilization of glomerular filtration rate. The second case is a 16-year-old girl, with recurrent episodes of renal colic. At diagnosis, she had obstructive hydronephrosis, multiple kidney stones and an estimated glomerular filtration of 42.1mL/min/1.73m2. Metabolic study showed hypocitraturia and hyperoxaluria. With dietetic measures and irregular treatment, urine oxalate excretion remained high but renal function improved. Genetic tests confirmed the presence of two pathologic variants in AGXT gene: c.731T>C and c.1151T>C in compound heterozygous. Conclusions: Recurrent urolithiasis and nephrocalcinosis in children along with family history/consanguinity should raise the suspicion of Primary Hyperoxaluria type 1. Conservative treatment may increase renal survival. Effects of systemic oxalosis must be screened when glomerular filtration rate declines below 30-50mL/min/1.73m2, and sequential or combined liver and kidney transplantation should be considered.

Introduction and Aims: Nephrocalcinosis is characterized by the deposition of calcium in the kidney parenchyma and tubules. The renal prognosis depends on the underlying cause, emphasizing the importance of its identification. We aim to review the data of children with nephrocalcinosis concerning etiology, clinical manifestations, growth and renal function at presentation and outcomes. Methods: Retrospective study of the records of children (<18 years) with nephrocalcinosis followed by a pediatric nephrology unit of level III hospital, between 2008-17. Clinical features, etiology, treatment and outcomes were evaluated. Results: We identified 35 cases: 24 isolated (69%) and 11 with nephrolithiasis (31%). The group was mostly constituted of girls (54%). Median age at presentation was 6 years (7 months - 17 years old); 40% of patients were under 2 years of age, 31% between 3 and 9 years and 29% older than 10 years. Mean follow-up was 4 years (1-9). The most common clinical manifestation was failure to thrive in the first year of life (34%) and flank or abdominal pain (20%); in 23% it was an incidental finding. Eleven percent of patients had a systemic syndromic disease. Renal function at diagnosis was normal in all children. The most frequent causes were metabolic abnormalities (23%), hereditary tubulopathies (23%), prematurity (20%) and pharmacologic (14%). Eleven percent were considered idiopathic. In a logistic regression analysis, sex, age of presentation and familiar history of nephrocalcinosis showed no correlation with nephrocalcinosis, nephrocalcinosis and nephrolithiasis or hereditary/metabolic etiologies. Discussion: Despite the small sample, in this study, the hereditary and/or metabolic disorders were the main cause of nephrocalcinosis. Associated symptoms and comorbidities, such as prematurity, growth retardation, intestinal malabsorption, or bone demineralization, should be evaluated for diagnostic purposes. No patient developed chronic kidney disease.

Introduction and Aims: Nephrolithiasis incidence in children has increased considerably. It is associated with substantial morbidity, recurrence and increased adulthood cardiovascular risk and chronic kidney disease. A thorough investigation is essential, as rare forms of urolithiasis have increased risk of renal failure. We aim to determine the epidemiology and outcomes of a pediatric population with nephrolithiasis presented in a nephrology unit of a tertiary centre. Methods: Retrospective study of the records of all children (<18 years) with nephrolithiasis diagnosis between 2008-17. Clinical features, etiology, recurrence, treatment, and outcomes were evaluated and compared throughout the study period through two equal periods (2008-12 versus 2013-17). Results: We identified 80 cases: isolated nephrolithiasis (86%) and associated with nephrocalcinosis (14%). Mean follow-up was 36 months (14-120). Median age at presentation was 8.6 years [3 months - 17 years]: 21% < 2 years-old and 46% ≥ 10 years. The annual ratio of referrals for nephrolithiasis increased on average 1.2% per year [0.3-11.8%]. Multiple etiological factors were present in 34%. A metabolic abnormality was identified in 54%: hypocitraturia (34%), hypercalcuria (24%), hyperoxaluria (15%), hyperuricosuria (15%) and cystinuria (1%), without age predominance (p=0.2). Urinary tract infection (24%) was the next most significant etiology and was more frequent below 2 years of age (p=0.001) and associated with struvite calculi (p=0.033). Median age at diagnosis was significantly lower in the study’s first half (5 vs 10 years; p=0.019) and an infectious etiology was more frequent (p=0.043). In a logistic-regression analysis, a family history of nephrolithiasis was associated with a metabolic cause (p<0.01). Sixty-three percent became stone free and 24% had recurrence. Discussion: Nephrolithiasis new referrals gradually increased throughout the study period. The most common etiology was metabolic, which is usually responsible for nephrolithiasis appearance and its recurrence, emphasizing the need for a complete evaluation.

Pheochromocytoma and renal artery stenosis are surgically treatable causes of hypertension. Although rare, the coexistence of pheochromocytoma and renal artery stenosis has been described in case reports. Common pathophysiological mechanisms other than extrinsic compression may be involved in this association, such as catecholamine-induced vasospasm. The early recognition of the association of pheochromocytoma with renal artery stenosis is essential for appropriate treatment planning. We present the case of a previously healthy tenyear-old boy who presented with hypertensive encephalopathy, tachycardia and diaphoresis. Hypertension was found to be secondary to a catecholamine-producing tumor associated with coexisting renal artery stenosis. Hypertension resolved a few months after successful pheochromocytoma excision, without renal artery revascularization

A acidose tubular renal distal é uma doença rara, caracterizada pela incapacidade na acidificação da urina, condicionando acidose metabólica hiperclorémica, hipocaliémia, hipercalciúria e nefrocalcinose, o que poderá causar atraso de crescimento, alteração do metabolismo ósseo e insuficiência renal crónica. A acidose tubular renal distal associada a surdez neurossensorial é uma doença de herança autossómica recessiva, causada por mutações do gene que codifica a subunidade B1 da H+ -ATPase (ATP6V1B1). Os autores relatam os casos de duas irmãs que apresentaram má progressão ponderal, alterações iónicas, do equilíbrio ácido base e surdez neurossensorial. Foi detectada em ambas as crianças a mutação homozigótica no gene ATP6V1B1. Com estes dois casos pretende-se destacar a importância de um diagnóstico precoce nesta patologia rara

Distal renal tubular acidosis is a rare disorder characterized by the inability in acidification of urine, conditioning hyperchloraemic acidosis, hypokalaemia, hypercalciuria and nephrocalcinosis, which can cause growth retardation, abnormal bone metabolism and, when untreated, chronic renal failure. Distal renal tubular acidosis and sensorineural deafness is an autosomal recessive disease caused by mutations in the gene encoding B1 subunit of H+ -ATPase (ATP6V1B1). The authors report the cases of two sisters who presented failure to thrive, changes in ionic and acid-base balance and sensorineural deafness. A homozygous mutation in ATP6V1B1 gene was detected in both girls. These two cases are intended to highlight the importance of an early diagnosis in this rare disease