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PLoS One 2022 30;17(6):e0250137. Epub 2022 Jun 30.

Buck Institute for Research on Aging, Novato, CA, United States of America.

Cystinuria is one of various disorders that cause biomineralization in the urinary system, including bladder stone formation in humans. It is most prevalent in children and adolescents and more aggressive in males. There is no cure, and only limited disease management techniques help to solubilize the stones. Read More

Mol Syndromol 2022 May 3;13(3):240-245. Epub 2022 Feb 3.

Department of Pediatric Metabolism, Faculty of Medicine, Ankara University, Ankara, Turkey.

Introduction: Hypotonia-cystinuria syndrome is a contiguous gene deletion syndrome that is characterized by hypotonia, developmental delay, and cystinuria type A. We present a male patient who was admitted to our center with clinical findings of hypotonia-cystinuria syndrome and diagnosed with megaconial congenital muscular dystrophy and cystinuria.

Case Presentation: A 16-month-old male patient was admitted with complaints of restlessness and body laxity. Read More

Prostaglandins Other Lipid Mediat 2022 Jun 6;162:106651. Epub 2022 Jun 6.

Shanghai Jiaotong University School of Medicine, China; Department of Pediatric Urology, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, China. Electronic address:

Cystinuria is a genetic disorder of cystine transport, including defective protein bAT (encoded by SLC7A9), and/or rBAT (encoded by SLC3A1). Patients present hyperexcretion of cystine in the urine, recurrent cystine lithiasis, and progressive decline in kidney function. Moreover, heterodimer transport is defective. Read More

Nat Commun 2022 May 16;13(1):2708. Epub 2022 May 16.

Department of Laboratory Medicine, The Jikei University School of Medicine, Tokyo, 105-8461, Japan.

Cystinuria is a genetic disorder characterized by overexcretion of dibasic amino acids and cystine, causing recurrent kidney stones and kidney failure. Mutations of the regulatory glycoprotein rBAT and the amino acid transporter bAT, which constitute system b, are linked to type I and non-type I cystinuria respectively and they exhibit distinct phenotypes due to protein trafficking defects or catalytic inactivation. Here, using electron cryo-microscopy and biochemistry, we discover that Ca mediates higher-order assembly of system b. Read More

Urolithiasis 2022 Jun 13;50(3):279-291. Epub 2022 Apr 13.

Department of Pediatric Urology, Xinhua Hospital Affiliated To Shanghai Jiao Tong University School of Medicine, 1665 KongJiang Road, Shanghai, 200092, China.

Cystinuria is a genetic disorder of cystine transport that accounts for 1-2% of all cases of renal lithiasis. It is characterized by hyperexcretion of cystine in urine and recurrent cystine lithiasis. Defective transport of cystine into epithelial cells of renal tubules occurs because of mutations of the transport heterodimer, including protein bAT (encoded by SLC7A9) and rBAT (encoded by SLC3A1) linked through a covalent disulfide bond. Read More

Anticancer Agents Med Chem 2022 Apr 4. Epub 2022 Apr 4.

Chitkara College of Pharmacy, Chitkara University, Punjab, India.

Background: The side effects reported from ionising radiation are skin changes,dry mouth, hair loss, low blood count, and the mutagenic effect on normal cells when given as radiotherapy for cancer treatment. These radiations cause damage to the cell membrane, lipids, proteins, and DNA and generate free radicals. Evidence reports state that radiotherapy accounts for 17-19% of secondary malignancies, labelling this treatment option as a double-edged sword. Read More

N Engl J Med 2022 Mar;386(12):1165

Lausanne University Hospital, Lausanne, Switzerland

Amino Acids 2022 Mar 16. Epub 2022 Mar 16.

Eenheid Algemene Chemie (ALGC), Materials Modeling Group, Vrije Universiteit Brussel (VUB), Pleinlaan 2, 1050, Brussel, Belgium.

It is assumed that genetic diseases affecting the metabolism of cysteine and the kidney function lead to two different kinds of pathologies, namely cystinuria and cystinosis whereby generate L-cystine crystals. Recently, the presence of L-cysteine crystal has been underlined in the case of cystinosis. Interestingly, it can be strikingly seen that cystine ([-S-CH-CH-(NH)-COOH]) consists of two cysteine (CHNOS) molecules connected by a disulfide (S-S) bond. Read More

JIMD Rep 2022 Mar 27;63(2):146-161. Epub 2022 Jan 27.

Sección de Gastroenterología y Nutrición Hospital Infantil Universitario Niño Jesús Madrid Spain.

We present the results of our experience in the diagnosis of inborn errors of metabolism (IEM) since the Expanded Newborn Screening was implemented in our Region. Dried blood samples were collected 48 h after birth. Amino acids and acylcarnitines were quantitated by mass spectrometry (MS)/MS. Read More

Front Pediatr 2021 23;9:822114. Epub 2022 Feb 23.

Pediatrics, Grenoble University Hospital, Grenoble, France.

Cystinuria is a recessively inherited genetic disease causing recurrent kidney stones with risk of kidney failure. The discovery of hyperechoic colonic content on an antenatal ultrasound is considered to be a pathognomic sign of cystinuria. Herein, we present a clinical case with antenatal diagnosis of cystinuria in an ultrasound finding, which eventually revealed a multisystem disease, characterized by the association of renal Fanconi syndrome, hyperinsulinemic hypoglycemia, and hepatic dysfunction. Read More

Rheumatology (Oxford) 2022 Feb 25. Epub 2022 Feb 25.

Department of Rheumatology, Royal Wolverhampton Hospitals NHS Trust, Wolverhampton, UK.

Front Pediatr 2021 17;9:736308. Epub 2022 Jan 17.

Pediatric Nephrology Center of Excellence, Department of Pediatrics, King Abdulaziz University, Jeddah, Saudi Arabia.

Renal stones (nephrolithiasis and urolithiasis) and nephrocalcinosis are uncommon in children; however, their incidences in pediatric populations have been increasing. This multicenter retrospective study compared the clinical presentation, etiology, and outcomes of childhood nephrolithiasis or urolithiasis with those of nephrocalcinosis. The study included 144 children: 93 with renal stones and 51 with nephrocalcinosis. Read More

Acc Chem Res 2022 02 28;55(4):516-525. Epub 2022 Jan 28.

Department of Chemistry and Molecular Design Institute, New York University, 100 Washington Square East, New York, New York 10003-6688, United States.

Aberrant crystallization within the human body can lead to several disease states or adverse outcomes, yet much remains to be understood about the critical stages leading to these events, which can include crystal nucleation and growth, crystal aggregation, and the adhesion of crystals to cells. Kidney stones, which are aggregates of single crystals with physiological origins, are particularly illustrative of pathological crystallization, with 10% of the U.S. Read More

Urolithiasis 2022 Apr 27;50(2):229-234. Epub 2022 Jan 27.

Urology Department, Fundació Puigvert, Carrer de Cartagena, 340-350, 08025, Barcelona, Spain.

Cystinuria, which is the cause of cystine urolithiasis, accounts for 2-6% of all urinary stones in children, has a low prevalence with a high recurrence rate, making this metabolic disorder a therapeutic challenge in pediatric population. The aim of this work is evaluate the efficacy and safety of retrograde intra-renal surgery (RIRS) in pediatric patients with cystinuria and kidney stones smaller than 2 cm. Prospective study of 64 stones treated in 22 retrograde intra-renal surgeries (RIRS) in cystinuric pediatric patients with renal or proximal ureteral stones less than 2 cm. Read More

Saudi Med J 2022 Jan;43(1):81-90

From the Department of Pediatrics (Kari, Shalaby), Pediatric Nephrology Center of Excellence; from the Department of Medicine (Qari), King Abdulaziz University, from King Abdullah International Medical Research Center (Albanna), King Saud Bin Abdulaziz University for Health Sciences, Jeddah, and from the Department of Pediatric (Alhasan), College of Medicine, King Saud University, Riyadh, Kingdom of Saudi Arabia.

Objectives: To study childhood nephrolithiasis and nephrocalcinosis caused by metabolic disorders, distal renal tubular acidosis (dRTA), and familial hypomagnesemia, hypercalciuria, and nephrocalcinosis (FHHNC).

Methods: We retrospectively evaluated 86 children presented over 10 years (2011-2021), with nephrolithiasis (89%) and nephrocalcinosis (11%) caused by metabolic disorders (62%), FHHNC (21%), and dRTA (17%).

Results: The mean age at discovery was 72. Read More

Curr Opin Nephrol Hypertens 2022 03;31(2):175-179

Department of Cell and Developmental Biology, Vanderbilt University.

Purpose Of Review: The aim of this study was to summarize recent findings in kidney gene therapy while proposing cystinuria as a model kidney disease target for genome engineering therapeutics.

Recent Findings: Despite the advances of gene therapy for treating diseases of other organs, the kidney lags behind. Kidney-targeted gene delivery remains an obstacle to gene therapy of kidney disease. Read More

Yale J Biol Med 2021 12 29;94(4):681-686. Epub 2021 Dec 29.

Department of Medicine, University of Chicago, Chicago, IL, USA.

Cystinuria, accounting for about 1-2% of kidney stones in adults, carries significant morbidity beginning at a young age [1]. Cystine stone formers have more stone events compared to other stone formers, as well as more surgical interventions, potentially contributing to faster progression to chronic kidney disease (CKD), and end-stage kidney disease (ESKD) [2]. Successful medical therapy for cystine stone formers may be limited by adherence to the extensive lifestyle changes and the adverse side effect profiles of some interventions, leading to decreased quality of life for these patients relative to other stone formers. Read More

Front Pediatr 2021 16;9:763317. Epub 2021 Nov 16.

Department of Pediatric Surgery and Urology, Necker-Enfants Malades Hospital, APHP, Paris, France.

Cystinuria is a genetic disorder characterized by a defective reabsorption of cystine and dibasic amino acids leading to development of urinary tract calculi from childhood onward. Cystine lithiasis is known to be resistant to fragmentation. The aim was to evaluate our long-term experience with extracorporeal shockwave lithotripsy (ESWL) used as first-line urological treatment to treat cystine stones in children. Read More

Biosensors (Basel) 2021 Oct 26;11(11). Epub 2021 Oct 26.

Institute of Applied Chemistry and Department of Chemistry, Hallym University, Chuncheon 24252, Korea.

The measurement of cysteine in human urine and live cells is crucial for evaluating biological metabolism, monitoring and maintaining the immune system, preventing tissue/DNA damage caused by free radicals, preventing autoimmune diseases, and diagnosing disorders such as cystinuria and cancer. A method that uses a fluorescence turn-on probe and a portable fluorescence spectrometer device are crucial for highly sensitive, simple, rapid, and inexpensive cysteine detection. Herein, we present the synthesis and application of a benzimidazole-based fluorescent probe () along with the design and development of a portable fluorescence spectrometer device () for detecting cysteine in simulated human urine. Read More

Pediatr Nephrol 2022 Aug 23;37(8):1705-1711. Epub 2021 Nov 23.

Dipartimento Di Scienze Mediche E Chirurgiche, U.O.S. Terapia Conservativa Della Malattia Renale Cronica, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo Agostino Gemelli 8, U.O.C. Nefrologia, 00168, Rome, Italy.

Cystinuria is the most common genetic cause of nephrolithiasis in children. It is considered a heritable aminoaciduria as the genetic defect affects the reabsorption of cystine and three other amino acids (ornithine, lysine, and arginine) in the renal proximal tubule. Patients affected by this condition have elevated excretion of cystine in the urine, and because of this amino acid's low solubility at normal urine pH, patients tend to form cystine calculi. Read More

Iran J Public Health 2021 Sep;50(9):1897-1901

Department of Medical Genetic, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

Cystinuria is an autosomal recessive disorder in which the renal reabsorption of cystine, arginine, lysine and ornithine are disturbed. The two genes, the pathogenic forms of which are responsible for the disorder, are SLC7A9 and SLC3A1. In this study, we describe a disease that has a new c. Read More

Molecules 2021 Oct 15;26(20). Epub 2021 Oct 15.

Laboratory of Amino Acid Transporters and Disease, Institute for Research in Biomedicine (IRB Barcelona), The Barcelona Institute of Science and Technology (BIST), Baldiri Reixac 10, 08028 Barcelona, Spain.

It is known that 4F2hc and rBAT are the heavy subunits of the heteromeric amino acid transporters (HATs). These heavy subunits are -glycosylated proteins, with an N-terminal domain, one transmembrane domain and a bulky extracellular domain (ectodomain) that belongs to the α-amylase family. The heavy subunits are covalently linked to a light subunit from the SLC7 family, which is responsible for the amino acid transport activity, forming a heterodimer. Read More

CEN Case Rep 2022 May 20;11(2):216-219. Epub 2021 Oct 20.

Department of Pediatric Nephrology, Tokyo Women's Medical University, Tokyo, Japan.

Cystinuria is an autosomal recessive disorder characterized by a decrease in the reabsorption of cystine and dibasic amino acids (lysine, ornithine, and arginine) in the renal proximal tubule. It presents with recurrent urolithiasis. Cystinuria accounts for 6-8% of all pediatric urolithiasis. Read More

Anal Chim Acta 2021 Nov 2;1184:339017. Epub 2021 Sep 2.

Zhejiang Provincial Key Laboratory of Advanced Mass Spectrometry and Molecular Analysis, Institute of Mass Spectrometry, School of Material Science and Chemical Engineering, Ningbo University, Ningbo, Zhejiang, 315211, China. Electronic address:

Penicillamine (Pen) is a common chiral drug that is obtained from penicillin. Between the two enantiomers of Pen, only D-Pen can be used to treat cystinuria and rheumatoid arthritis while L-Pen is toxic. Therefore, it requires great efforts for the research of the rigorous analysis and distinction of the two enantiomers. Read More

Ann Clin Transl Neurol 2021 11 6;8(11):2199-2204. Epub 2021 Oct 6.

Department of Neurology and Pediatrics, Columbia University Irving Medical Center, New York, NY, 10032.

Two siblings presented similarly with congenital hypotonia, lactic acidosis, and failure to thrive. Later in childhood, the brother developed cystinuria and nephrolithiasis whereas the older sister suffered from cystinuria and chronic neurobehavioral disturbances. Biopsied muscle studies demonstrated deficient cytochrome c oxidase activities consistent with a mitochondrial disease. Read More

Antioxidants (Basel) 2021 Sep 7;10(9). Epub 2021 Sep 7.

Human Molecular Genetics Laboratory, Gene, Disease and Therapy Program, IDIBELL, L'Hospitalet de Llobregat, 08908 Barcelona, Spain.

Cystinuria, a rare inherited aminoaciduria condition, is characterized by the hyperexcretion of cystine, ornithine, lysine, and arginine. Its main clinical manifestation is cystine stone formation in the urinary tract, being responsible for 1-2% total and 6-8% pediatric lithiasis. Cystinuria patients suffer from recurrent lithiasic episodes that might end in surgical interventions, progressive renal functional deterioration, and kidney loss. Read More

J Phys Chem B 2021 09 31;125(36):10344-10354. Epub 2021 Aug 31.

Robotic Research Laboratory, Centre of Excellence in Experimental Solid Mechanics and Dynamics, School of Mechanical Engineering, Iran University of Science and Technology, Tehran 1684613114, Iran.

Because cystine kidney stones are a more serious challenge for health-related quality of life than other types of kidney stones, the search for a new treatment for cystinuria is considered the main goal of this study. To achieve the defined goal, classical molecular dynamics simulations and quantum mechanics calculations were implemented in this study. Three nanodrills with different stiffnesses (i. Read More

Animals (Basel) 2021 Aug 19;11(8). Epub 2021 Aug 19.

Faculty of Veterinary Medicine, University of Veterinary Sciences, 612 42 Brno, Czech Republic.

The purpose of this review is to summarize current knowledge on canine and feline cystinuria from available scientific reports. Cystinuria is an inherited metabolic defect characterized by abnormal intestinal and renal amino acid transport in which cystine and the dibasic amino acids ornithine, lysine, and arginine are involved (COLA). At a normal urine pH, ornithine, lysine, and arginine are soluble, but cysteine forms a dimer, cystine, which is relatively insoluble, resulting in crystal precipitation. Read More

ACS Chem Neurosci 2021 09 18;12(17):3237-3249. Epub 2021 Aug 18.

Department of Chemistry, School of Science, Indrashil University, Kadi, Mehsana, Gujarat 382740, India.

There is a plethora of significant research that illustrates toxic self-assemblies formed by the aggregation of single amino acids, such as phenylalanine, tyrosine, tryptophan, cysteine, and methionine, and their implication on the etiology of inborn errors of metabolisms (IEMs), such as phenylketonuria, tyrosinemia, hypertryptophanemia, cystinuria, and hypermethioninemia, respectively. Hence, studying the aggregation behavior of single amino acids is very crucial from the chemical neuroscience perspective to understanding the common etiology between single amino acid metabolite disorders and amyloid diseases like Alzheimer's and Parkinson's. Herein we report the aggregation properties of nonaromatic single amino acids l-proline (Pro), l-hydroxyproline (Hyp), and l-lysine hydrochloride (Lys). Read More

Fish Physiol Biochem 2021 Oct 2;47(5):1507-1525. Epub 2021 Aug 2.

Department of Biological Sciences, University of Bergen, Postbox 7803, N-5020, Bergen, Norway.

System b absorbs lysine, arginine, ornithine, and cystine, as well as some (large) neutral amino acids in the mammalian kidney and intestine. It is a heteromeric amino acid transporter made of the heavy subunit SLC3A1/rBAT and the light subunit SLC7A9/bAT. Mutations in these two genes can cause cystinuria in mammals. Read More