Dent Disease Type 1: Still an Under-Recognized Renal Proximal Tubulopathy: A Case Report

Dent disease is a rare renal tubular disorder that appears almost exclusively in males. The diagnosis is still challenging, and therefore Dent disease is occasionally misdiagnosed. We report a case of a 45-year-old man with Dent disease who developed renal failure. Since the age of 7 months, he persistently exhibited proteinuria. At the age of 24 years, he underwent kidney biopsy, which revealed focal segmental glomerulosclerosis. The patient’s brother was found to have proteinuria since he was 2 years old. At the age of 45 years, the patient was transferred to a tertiary care nephrologist, and Dent disease was suspected. Genetic testing revealed a CLCN5 mutation. We highlight the broad spectrum of clinical manifestations in Dent disease and the importance of having a high clinical suspicion to attain a definitive diagnosis. Furthermore, future research regarding the clinical course of the disease, prognosis, and effective treatment options is needed

Dent disease type 1: still an under-recognized renal proximal tubulopathy: a case report

Dent disease is a rare renal tubular disorder that appears almost exclusively in males. The diagnosis is still challenging, and therefore Dent disease is occasionally misdiagnosed. We report a case of a 45-year-old man with Dent disease who developed renal failure. Since the age of 7 months, he persistently exhibited proteinuria. At the age of 24 years, he underwent kidney biopsy, which revealed focal segmental glomerulosclerosis. The patient’s brother was found to have proteinuria since he was 2 years old. At the age of 45 years, the patient was transferred to a tertiary care nephrologist, and Dent disease was suspected. Genetic testing revealed a CLCN5 mutation. We highlight the broad spectrum of clinical manifestations in Dent disease and the importance of having a high clinical suspicion to attain a definitive diagnosis. Furthermore, future research regarding the clinical course of the disease, prognosis, and effective treatment options is needed

Complement inhibitor eculizumab in thrombotic microangiopathy: single-center case series

Our case series showed that eculizumab is efficacious and safe in treating thrombotic microangiopathy, as well as it has positive effects on quality of life. Further extensive studies are required to develop unified treatment guidelines

Genotype–Phenotype Correlation in a New Fabry-Disease-Causing Mutation

Background: Fabry disease (FD) is a rare X-linked inherited lysosomal storage disorder caused by α-galactosidase A deficiency leading to intracellular glycosphingolipid accumulation. FD manifestation is multisystem, and can differ depending on disease-related genetic variants. Currently, more than 700 different FD-causing mutations have been identified in the human GLA gene. We identified a novel mutation in a Lithuanian family with classical manifestations of Fabry disease, revealing severe effects to the cardiovascular systems of heterozygous women. Case presentation: A 49-year-old woman underwent echocardiography due to progressive dyspnea that lasted seven years, reduced physical activity, and periodic cardiac arrhythmia. Echocardiography revealed left ventricular hypertrophy with normal diastolic function. The patient had experienced acroparesthesia in her upper limbs and abdominal pain since childhood, and in the last decade had experienced mild proteinuria without renal failure. Her renal biopsy was typical for Fabry disease. The patient’s brain magnetic resonance imaging (MRI) (T2 flair) showed white matter hyperintensities lesions. DNA sequencing of the proband, her mother and one of her sons showed a novel GLA gene exon 2 mutation, c.270C>G (p.Cys90Trp). All three patients had decreased α-galactosidase A activity and specific FD manifestations. Conclusions: A novel GLA mutation, c.270C>G (p.Cys90Trp), was found in a Lithuanian family with a classical form of Fabry disease in heterozygous women with predominant cardiac involvement. However, the exact manifestation of this mutation is still unclear as it is newly reported and further research must be done

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