ABSTRACT
3-methylglutaconic aciduria includes a heterogeneous group of inborn errors of metabolism. The disease may have various clinical presentations, as can duplication 5q. We present the case of a 13-year-old boy with 3-methylglutaconic aciduria and duplication 5q. The main symptoms included myopathy, weakness, spastic paresis intensified mostly in the lower limbs, and intellectual disability. Additional studies showed elevated levels of 3-methylglutaconic acid in urine and ammonia in plasma. A duplication in region 5q23.3q31.1 was found in array-based comparative genomic hybridization. Next-generation sequencing did not reveal any pathological mutation. On the basis of the clinical picture and the results of biochemical and genetic tests 3-methylglutaconic aciduria type IV with duplication 5q was diagnosed.
Subject(s)
Abnormalities, Multiple/diagnosis , Cri-du-Chat Syndrome/complications , Cri-du-Chat Syndrome/diagnosis , Metabolism, Inborn Errors/complications , Metabolism, Inborn Errors/diagnosis , Trisomy/diagnosis , Abnormalities, Multiple/blood , Abnormalities, Multiple/urine , Adolescent , Ammonia/blood , Chromosomes, Human, Pair 5/genetics , Comparative Genomic Hybridization , Cri-du-Chat Syndrome/genetics , Glutarates/urine , High-Throughput Nucleotide Sequencing , Humans , Male , Metabolism, Inborn Errors/blood , Metabolism, Inborn Errors/urine , Rare Diseases/blood , Rare Diseases/complications , Rare Diseases/diagnosis , Rare Diseases/urine , Trisomy/geneticsSubject(s)
Alkaptonuria/drug therapy , Clinical Trials as Topic/methods , Clinical Trials as Topic/standards , Compassionate Use Trials , Rare Diseases/drug therapy , Adolescent , Alkaptonuria/genetics , Alkaptonuria/metabolism , Alkaptonuria/urine , Animals , Autopsy , Child , Clinical Trials as Topic/economics , Cyclohexanones/pharmacology , Cyclohexanones/therapeutic use , Disease Models, Animal , Disease Progression , Drug Approval , Endpoint Determination , Female , Homogentisic Acid/metabolism , Humans , Infant , Male , Mice , National Health Programs , National Institutes of Health (U.S.) , Nitrobenzoates/pharmacology , Nitrobenzoates/therapeutic use , Observational Studies as Topic , Off-Label Use , Orphan Drug Production , Rare Diseases/genetics , Rare Diseases/metabolism , Rare Diseases/urine , Rats , Sample Size , Tyrosine/metabolism , Tyrosinemias/drug therapy , Tyrosinemias/enzymology , United States , United States Food and Drug Administration/legislation & jurisprudenceABSTRACT
The National Institutes of Health (NIH) Undiagnosed Diseases Program (UDP) studies rare genetic disorders not only to achieve diagnoses, but to understand human biology. To ascertain the contribution of protein glycosylation to rare diseases, the NIH UDP used mass spectrometry to agnostically identify abnormalities of N-linked and O-linked glycans in plasma and free oligosaccharides in the urine of 207 patients. 60% of UDP patients had a glycome profile that deviated from control values in at least 1 fluid. Additional evaluation of the fibroblast glycome in 66 patients with abnormalities in plasma and/or urine revealed a consistent glycome phenotype in 83% of these cases. Many of these patients may have secondary glycosylation defects, since it is unlikely that they all have congenital disorders of glycosylation (CDGs). In fact, whole exome sequencing revealed only a few patients with CDGs, along with several others having disorders indirectly altering glycosylation. In summary, we describe a biochemical phenotyping screen to identify defects in protein glycosylation that can elucidate mechanisms of disease among NIH UDP patients.
Subject(s)
Glycomics , Rare Diseases/diagnosis , Rare Diseases/metabolism , Humans , Phenotype , Rare Diseases/blood , Rare Diseases/urineABSTRACT
PURPOSE: We set out to facilitate the molecular diagnosis of patients with PIK3CA-related overgrowth spectrum (PROS), a heterogeneous somatic disorder characterized by variable presentations of segmental overgrowth, vascular malformations, skin lesions, and nephroblastomatosis, rare precursor lesions to Wilms tumor. Molecular diagnosis of PROS is challenging due to its mosaic nature, often requiring invasive biopsies. METHODS: Digital droplet polymerase chain reaction (ddPCR) was used to analyze tissues including urine, saliva, buccal cells, and blood, from eight patients with PROS. Further analyses were performed on plasma and urine cell-free DNA (cfDNA). RESULTS: PIK3CA variants were detected in plasma cfDNA at levels up to 0.5% in 50% of tested samples. In addition, high levels of PIK3CA variants in urine cfDNA correlated with a history of nephroblastomatosis compared with patients without renal involvement (P < 0.05). CONCLUSION: Digital droplet PCR is a sensitive molecular tool that enables low-level variant detection of PIK3CA in various tissue types, providing an alternative diagnostic method. Furthermore, urine cfDNA is a candidate biomarker for nephroblastomatosis in PROS, which may be useful to refine screening guidelines for tumor risk in these patients.
Subject(s)
Cell-Free Nucleic Acids/blood , Cell-Free Nucleic Acids/urine , Fetal Macrosomia/urine , Wilms Tumor/urine , Adult , Biomarkers/urine , Child , Child, Preschool , Class I Phosphatidylinositol 3-Kinases/genetics , Class I Phosphatidylinositol 3-Kinases/metabolism , Female , Fetal Macrosomia/genetics , Genetic Association Studies , Growth Disorders/diagnosis , Growth Disorders/genetics , Humans , Male , Mutation , Rare Diseases/genetics , Rare Diseases/urine , Wilms Tumor/geneticsABSTRACT
BACKGROUND: Nephrotic-range proteinuria as a paraneoplastic syndrome (PNS) is an exceptional presentation, especially in children. It is usually associated with hematologic malignancies. Solid tumors are very rare causes of proteinuria. CASE-DIAGNOSIS/TREATMENT: We present the case of a 7-year-old boy with an extremely rare atypical thymic carcinoid accompanied by nephrotic-range proteinuria as PNS. The kidney biopsy was consistent with minimal change disease (MCD). Tests for a neuroendocrine tumor were performed due to symptoms of hypercortisolemia and an elevated concentration of chromogranin A in the serum. The chest computed tomography revealed a tumor in the anterior mediastinum, which was diagnosed as an atypical thymic carcinoid. A complete resolution of the nephrotic-range proteinuria was observed within 1 week after the first thoracoscopic surgery, with almost complete reduction of the tumor mass. CONCLUSIONS: This extremely rare case shows that MCD can occur as a PNS even in children. Nephrotic-range proteinuria can be a symptom of malignant solid tumor. This case highlights the possibility of secondary causes of MCD in children.
Subject(s)
Carcinoid Tumor/complications , Paraneoplastic Syndromes/urine , Proteinuria/etiology , Rare Diseases/complications , Thymus Neoplasms/complications , Adrenocorticotropic Hormone/blood , Biopsy , Carcinoid Tumor/diagnosis , Carcinoid Tumor/surgery , Carcinoid Tumor/urine , Child , Chromogranin A/urine , Cushing Syndrome/diagnosis , Diagnosis, Differential , Humans , Hydroxyindoleacetic Acid/urine , Hyperglycemia/etiology , Hypernatremia/etiology , Hypertension/etiology , Hypokalemia/etiology , Kidney/pathology , Kidney/ultrastructure , Magnetic Resonance Imaging , Male , Microscopy, Electron , Nephrotic Syndrome/diagnosis , Paraneoplastic Syndromes/diagnosis , Proteinuria/urine , Rare Diseases/diagnosis , Rare Diseases/surgery , Rare Diseases/urine , Thoracoscopy , Thymus Neoplasms/diagnosis , Thymus Neoplasms/surgery , Thymus Neoplasms/urine , Tomography, X-Ray ComputedSubject(s)
Collagen Type III/metabolism , Glomerular Mesangium/pathology , Kidney Diseases/pathology , Nail-Patella Syndrome/pathology , Rare Diseases/pathology , Biopsy , Creatinine/blood , Diagnosis, Differential , Female , Fluorescent Antibody Technique , Glomerular Mesangium/ultrastructure , Hematuria/urine , Humans , Kidney Diseases/blood , Kidney Diseases/diagnosis , Kidney Diseases/urine , Middle Aged , Nail-Patella Syndrome/diagnosis , Periodic Acid-Schiff Reaction , Proteinuria/urine , Rare Diseases/blood , Rare Diseases/diagnosis , Rare Diseases/urineABSTRACT
Chyluria is an uncommon condition characterized by lymphatic fluid excretion into the urinary tract. Most common causes of chyluria are infections by parasites e.g. filariasis, echinococcosis, or cysticercosis. Nonparasitic chyluria is a very rare condition and possible etiologies include granulomatous disease (e.g. tuberculosis, leprosy, and fungal infection), malignomes, inherited and acquired malformation (posttraumatic), pregnancy, or aortic aneurysm. We present a case of a 73-year-old man, born and raised in Taiwan, but living in Austria for the past 5 years. He was admitted in our department by a general practitioner due to milky urine, whose turbidity increased after meal. All tests for infectious diseases or other above-mentioned causes remained negative. Additionally, although flexible cystoscopy yielded in a clear diagnosis of a milky urine jet out of the right urether, CT urography and bipedal lymphangiography failed to locate the lymphorenal fistula. Due to a stable renal function and absence of lipid metabolism disorders, a conservative management of the patient was chosen.