Polycystic renal disease : an update

La enfermedad renal poliquística (PKD) es una enfermedad genética común que consiste en la aparición progresiva de lesiones quísticas en los riñones, que remplazan el parénquima renal, lo que conduce a enfermedad renal crónica terminal. La PKD tiene dos patrones de herencia: autosómico dominante y autosómico recesivo. La forma autosómica dominante es más común y menos grave que la autosómica recesiva. Se conoce que la PKD es causada por mutación en varios loci humanos. La forma autosómica dominante puede ser causada por mutaciones en dos genes diferentes (PKD1 y PKD2); en tanto que la forma autosómica recesiva solo tiene un gen causal (PKHD1). Existen numerosas publicaciones que buscan explicar la fisiopatología de la enfermedad. Esto refleja un esfuerzo internacional por comprender la naturaleza de la enfermedad, para desarrollar terapias que eviten la aparición de los quistes o la progresión de los que ya están instaurados. El objetivo de esta revisión es difundir el conocimiento que se tiene hasta el momento, acerca de la enfermedad renal poliquística. Por lo tanto, realizamos un breve recuento de las características clínicas de la enfermedad y el tratamiento actual disponible.Artículo de revisión53-68Polycystic Kidney Disease (PKD) is a common genetic condition, which is characterized by gradual appearance of multiple cysts in the kidneys; this causes the destruction of renal parenchyma leading to chronic renal disease. PKD has two patterns of inheritance: autosomal dominant and autosomal recessive. The autosomal dominant form is more common and less severe than the autosomal recessive. It is known that PKD is caused by mutation in several human loci. The autosomal dominant form can be caused by mutations in 2 different genes (PKD1 and PKD2). The autosomal recessive form has only one causal gene (PKHD1). There are numerous publications worldwide that seek to explain the pathophysiology of the disease; this reflects an international effort to understand the nature of the disease, to develop therapies to prevent the appearance of cysts or the progression of those already existent lesions. The objective of this review is to update the knowledge we have so far, about polycystic kidney disease therefore we decided to conduct a brief review of the clinical features of disease and the treatment available today

Global birth defects app: An innovative tool for describing and coding congenital anomalies at birth in low resource settings

BACKGROUND: Surveillance programs in low- and middle-income countries (LMICs) have difficulty in obtaining accurate information about congenital anomalies. METHODS: As part of the ZikaPLAN project, an International Committee developed an app for the description and coding of congenital anomalies that are externally visible at birth, for use in low resource settings. The “basic” version of the app was designed for a basic clinical setting and to overcome language and terminology barriers by providing diagrams and photos, sourced mainly from international Birth Defects Atlases. The “surveillance” version additionally allows recording of limited pseudonymized data relevant to diagnosis, which can be uploaded to a secure server, and downloaded by the surveillance program data center. RESULTS: The app contains 98 (88 major and 10 minor) externally visible anomalies and 12 syndromes (including congenital Zika syndrome), with definitions and International Classification of Disease v10 -based code. It also contains newborn examination videos and links to further resources. The user taps a region of the body, then selects among a range of images to choose the congenital anomaly that best resembles what they observe, with guidance regarding similar congenital anomalies. The “basic” version of the app has been reviewed by experts and made available on the Apple and Google Play stores. Since its launch in November 2019, it has been downloaded in 39 countries. The "surveillance” version is currently being field-tested. CONCLUSION: The global birth defects app is a mHealth tool that can help in developing congenital anomaly surveillance in low resource settings to support prevention and care

At a glance:the largest Niemann-Pick type C1 cohort with 602 patients diagnosed over 15 years

Niemann-Pick type C1 disease (NPC1 [OMIM 257220]) is a rare and severe autosomal recessive disorder, characterized by a multitude of neurovisceral clinical manifestations and a fatal outcome with no effective treatment to date. Aiming to gain insights into the genetic aspects of the disease, clinical, genetic, and biomarker PPCS data from 602 patients referred from 47 countries and diagnosed with NPC1 in our laboratory were analyzed. Patients’ clinical data were dissected using Human Phenotype Ontology (HPO) terms, and genotype–phenotype analysis was performed. The median age at diagnosis was 10.6 years (range 0–64.5 years), with 287 unique pathogenic/likely pathogenic (P/LP) variants identified, expanding NPC1 allelic heterogeneity. Importantly, 73 P/LP variants were previously unpublished. The most frequent variants detected were: c.3019C &gt; G, p.(P1007A), c.3104C &gt; T, p.(A1035V), and c.2861C &gt; T, p.(S954L). Loss of function (LoF) variants were significantly associated with earlier age at diagnosis, highly increased biomarker levels, and a visceral phenotype (abnormal abdomen and liver morphology). On the other hand, the variants p.(P1007A) and p.(S954L) were significantly associated with later age at diagnosis (p &lt; 0.001) and mildly elevated biomarker levels (p ≤ 0.002), consistent with the juvenile/adult form of NPC1. In addition, p.(I1061T), p.(S954L), and p.(A1035V) were associated with abnormality of eye movements (vertical supranuclear gaze palsy, p ≤ 0.05). We describe the largest and most heterogenous cohort of NPC1 patients published to date. Our results suggest that besides its utility in variant classification, the biomarker PPCS might serve to indicate disease severity/progression. In addition, we establish new genotype–phenotype relationships for “frequent” NPC1 variants.</p

Achalasia familiar : report of a family with an autosomal dominant pattern of inherence

Q3Q1Reporte de casoE1-E4Esophageal achalasia is a well-known pathology with an autosomal recessive pattern of inherence described in the familiar cases. Its principal symptom is dysphagia, secondary to the poor relaxation of the lower esophageal sphincter. Chagas disease is one of the many causes involved in the development of this disease, being of great importance in our country because of the high prevalence of the vector. Various syndromes include achalasia in their symptomatology, such as the triple A syndrome or Allgrove syndrome (Addisonianism, achalasia, and alacrimia). We reported a family with a classical autosomal pattern of inherence with six affected members, four men and two women, with achalasia diagnosis as well as esophagus cancer in two of them, secondary to the disease, and no other finding

An integrated multiomic approach as an excellent tool for the diagnosis of metabolic diseases: our first 3720 patients

To present our experience using a multiomic approach, which integrates genetic and biochemical testing as a first-line diagnostic tool for patients with inherited metabolic disorders (IMDs). A cohort of 3720 patients from 62 countries was tested using a panel including 206 genes with single nucleotide and copy number variant (SNV/CNV) detection, followed by semi-automatic variant filtering and reflex biochemical testing (25 assays). In 1389 patients (37%), a genetic diagnosis was achieved. Within this cohort, the highest diagnostic yield was obtained for patients from Asia (57.5%, mainly from Pakistan). Overall, 701 pathogenic/likely pathogenic unique SNVs and 40 CNVs were identified. In 620 patients, the result of the biochemical tests guided variant classification and reporting. Top five diagnosed diseases were: Gaucher disease, Niemann-Pick disease type A/B, phenylketonuria, mucopolysaccharidosis type I, and Wilson disease. We show that integrated genetic and biochemical testing facilitated the decision on clinical relevance of the variants and led to a high diagnostic yield (37%), which is comparable to exome/genome sequencing. More importantly, up to 43% of these patients ( n  = 610) could benefit from medical treatments (e.g., enzyme replacement therapy). This multiomic approach constitutes a unique and highly effective tool for the genetic diagnosis of IMDs