Inborn errors of immunity associated with characteristic phenotypes

Abstract Objectives: The aim of the report is to describe the main immunodeficiencies with syndromic characteristics according to the new classification of Inborn Errors of Immunity. Data source: The data search was centered on the PubMed platform on review studies, meta-analyses, systematic reviews, case reports and a randomized study published in the last 10 years that allowed the characterization of the several immunological defects included in this group. Data synthesis: Immunodeficiencies with syndromic characteristics include 65 immunological defects in 9 subgroups. The diversity of clinical manifestations is observed in each described disease and may appear early or later, with variable severity. Congenital thrombocytopenia, syndromes with DNA repair defect, immuno-osseous dysplasias, thymic defects, Hyper IgE Syndrome, anhidrotic ectodermal dysplasia with immunodeficiency and purine nucleoside phosphorylase deficiency were addressed. Conclusions: Immunological defects can present with very different characteristics; however, the occurrence of infectious processes, autoimmune disorders and progression to malignancy may suggest diagnostic research. In the case of diseases with gene mutations, family history is of utmost importance.

Identification of a novel mutation of UPB1 gene in a Chinese family affected with beta-ureidopropinoase deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular etiology for a Chinese family affected with beta-ureidopropinoase deficiency.@*METHODS@#Genomic DNA was extracted from the peripheral blood samples of family members. All exons and flanking intron regions of the UPB1 gene were amplified by PCR and detected by direct sequencing. The pathogenicity of identified mutation was analyzed using Polyphen2 and SIFT software.@*RESULTS@#Compound heterozygous mutations of the UPB1 gene, including c.853G>A (p.A285T) and c.917-1G>A, were discovered in the proband, which were inherited respectively from his mother and father. Bioinformatics analysis suggested that this novel mutation was damaging.@*CONCLUSION@#The compound heterozygous mutations of the UPB1 gene probably underlie the beta-ureidopropinoase deficiency in the infant. Discovery of c.853G>A also enriched the mutation spectrum of the UPB1 gene.

Analysis of UPB1 gene mutation in a family affected with beta-ureidopropinoase deficiency / 中华医学遗传学杂志

OBJECTIVE To detect potential mutation in a Chinese family affected with beta-ureidopropinoase deficiency. METHODS Genomic DNA was extracted from peripheral blood samples. All exons and flanking intron regions of the UPB1 gene were amplified by PCR and detected by direct sequencing. RESULTS A homozygous mutation c.977G>A was identified in exon 9 of the UPB1 gene in the proband. Both parents of the proband had heterozygous change of the same site. CONCLUSION The c.977G>A mutation of the UPB1 gene is responsible for the pathogenesis of the disease in the infant.

Neurotrophic keratitis in a patient with dihydroxypyrimidine dehydrogenase deficiency.

We describe a case of neurotrophic keratitis in association with dihydroxypyrimidine dehydrogenase (DHPD) deficiency. Ocular manifestations in patients with DHPD are rare and neurotrophic keratitis has never been reported before. A six-year-old boy who was a known case of DHPD deficiency and born of a consanguineous marriage presented to our clinic with non-healing corneal ulcers in both eyes. Reduced corneal sensations were detected and the patient was started on lubricating eye drops. The patient continues to be on lubricant eye drops and there has been no recurrence of the disease.

Xantinúria, nefrolitíase e insuficiência renal, relato de um caso / Xanthinuria, nephrolithiasis and kidney failure, a case report

Xantinúria é uma doença metabólica rara, caracterizada bioquimicamente por baixa produçäo de ácido úrico e acúmulo de xantina e hipoxantina no sangue. Como conseqüência, há uma quase ausência de ácido úrico na urina e elevada depuraçäo renal de oxipurinas. A deficiência isolada da atividade de enzima xantina oxidase é uma das causas possíveis. Cerca de 0,03 por cento dos cálculos urinários säo compostos por xantina, seja pura ou em associaçäo com ácido úrico, fosfato ou oxalato de cálcio. Descrevemos o caso de um paciente de 11 anos de idade, com insuficiência renal que formou vários cálculos urinários nos úlitmos quatro anos. Neste período o paciente apresentou infecçäo urinária recorrente e hematúria persistente. Näo havia história familiar de doença metabólica e nenhum outro membro da família havia formado cálculos renais. Uma informaçäo relevante é que os pais e os avós säo primos em primeiro grau. Os cálculos anteriormente retirados näo foram analisados. Há dois anos o paciente foi submetido a transplante renal, com boa evoluçäo clínica. Há 3 meses apresentou novos episódios de infecçäo urinária e hematúria macroscópica. Um ultrassom evidenciou atrofia bilateral dos rins remanescentes e um cálculo na bexiga, que foi retirado cirurgicamente. O cálculo analisado era de cor marrom, superfície lisa, forma oval e laminado no seu interior medindo 12 X 12 X 8 mm nos maiores diâmetros. As reaçöes para cálcio, oxalato, fosfato, magnésio, cistina, ácido úrico e amônia foram negativas. O teste para oxipurinas foi positivo.

Use of the urine uric acid to creatinine ratio for the detection of disorders of purine metabolism: normal values among 0 to 12 year old children

Os erros inatos do metabolismo das purinas näo säo usualmente identificados com a bateria de testes empregados para a detecçäo de distúrbios metabólicos. A aplicaçäo de um método simples de triagem desses distúrbios, a relaçäo ácido úrico/creatinina na urina, tem sido prejudicada pela inexistência de valores normais para a nossa populaçäo infantil e para as nossas condiçöes de laboratório. No presente trabalho, a relaçäo ácido úrico/creatinina é determinada em 72 crianças normais de 0 a 12 anos. O limite superior da normalidade pode ser estabelecido como de 1,22 para esta faixa etária, excluindo-se os recém-nascidos, que apresentaram valores em média mais elevados. Propöem-se que a relaçäo ácido/creatinina na urina seja incluída nos procedimentos usuais de triagem para erros inatos do metabolismo empregados em nosso meio