Search Our Scientific Publications & Authors

SLAS Discov 2019 Feb 27;24(2):111-120. Epub 2018 Dec 27.

1 In Vitro Biology, Integrated Drug Discovery, Sanofi-Genzyme, Waltham, MA, USA.

SLC6A19 (BAT1) is a neutral amino acid transporter, the loss of function of which results in Hartnup disease. SLC6A19 is also believed to have an important role in amino acid homeostasis, diabetes, and weight control. A small-molecule inhibitor of human SLC6A19 (hSLC6A19) was identified using two functional cell-based assays: a fluorescence imaging plate reader (FLIPR) membrane potential (FMP) assay and a stable isotope-labeled neutral amino acid uptake assay. Read More

BMC Pediatr 2014 Dec 20;14:311. Epub 2014 Dec 20.

Makassed Hospital, Alquds University, Medical College, Jerusalem, Palestine.

Background: Celiac disease (CD) is a complex autoimmune disorder that can lead to an inflammatory small intestinal villous atrophy and malabsorption. Hartnup disease is an autosomal recessive disorder caused by increased urinary excretion of neutral amino acids. Co-occurrence of Hartnup disease and CD is extremely rare with only a single case reported. Read More

Hum Mol Genet 2014 Dec 31;23(25):6935-43. Epub 2014 Jul 31.

deCODE Genetics, 101 Reykjavik, Iceland Faculty of Medicine

Chronic kidney disease (CKD) is a complex disorder with a strong genetic component. A number of common sequence variants have been found to associate with serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and/or CKD. We imputed 24 million single-nucleotide polymorphisms and insertions/deletions identified by whole-genome sequencing of 2230 Icelanders into 81 656 chip-typed individuals and 112 630 relatives of genotyped individuals over the age of 18 with SCr measurements. Read More

Microbes Infect 2013 Nov 17;15(13):866-73. Epub 2013 Aug 17.

IMBA, Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna, Austria.

The renin-angiotensin system (RAS) is a complex network that regulates blood pressure, electrolyte and fluid homeostasis, as well as the function of several organs. Angiotensin-converting enzyme 2 (ACE2) was identified as an enzyme that negatively regulates the RAS by converting Ang II, the main bioactive molecule of the RAS, to Ang 1-7. Thus, ACE2 counteracts the role of angiotensin-converting enzyme (ACE) which generates Ang II from Ang I. Read More

Handb Clin Neurol 2013 ;112:1213-7

Division of Pediatric Neurology, Department of Pediatrics, Duke University School of Medicine, Durham, NC, USA.

The approach to the child with ataxia requires a detailed history and careful general and neurological examination as well as selected blood work and brain imaging and increasingly available genetic testing for inherited ataxias that usually have an episodic or progressive presentation. The differential of acute and recurring ataxia covered in this chapter includes intoxication (e.g. Read More

Rev Neurol 2012 Apr;54(7):394-8

Hospital Sant Joan de Deu, 08950 Esplugues de Llobregat, Espana.

Introduction: Studying the amino acids in cerebrospinal fluid (CSF) is essential in the diagnosis of some neurological diseases and is an important aid in the diagnosis of others. No research has been published in the literature to prove the physiological relationship between the values of amino acids in CSF and plasma in the paediatric population.

Aim: To define a set of ratios for amino acids in plasma and CSF in the paediatric population that can be used in daily clinical practice. Read More

Channels (Austin) 2011 Sep-Oct;5(5):410-23. Epub 2011 Sep 1.

INRA/AgroParisTech, Paris, France.

Neutral amino acid transporters of the SLC6 family are expressed at the apical membrane of kidney and/or small intestine, where they (re-)absorb amino acids into the body. In this review we present the results concerning the dependence of their apical expression with their association to partner proteins. We will in particular focus on the situation of B0AT1 and B0AT3, that associate with members of the renin-angiotensin system (RAS), namely Tmem27 and angiotensin-converting enzyme 2 (ACE2), in a tissue specific manner. Read More

J Biol Chem 2011 Jul 2;286(30):26638-51. Epub 2011 Jun 2.

Research School of Biology, Australian National University, Canberra, Australian Capital Territory 0200, Australia.

Amino acid uptake in the intestine and kidney is mediated by a variety of amino acid transporters. To understand the role of epithelial neutral amino acid uptake in whole body homeostasis, we analyzed mice lacking the apical broad-spectrum neutral (0) amino acid transporter B(0)AT1 (Slc6a19). A general neutral aminoaciduria was observed similar to human Hartnup disorder which is caused by mutations in SLC6A19. Read More

Am J Physiol Gastrointest Liver Physiol 2011 Jul 24;301(1):G128-37. Epub 2011 Feb 24.

ZIEL Research Center of Nutrition and Food Sciences, Abteilung Biochemie, Technische Universität München, Freising, Germany.

The intestinal peptide transporter PEPT1 mediates the uptake of di- and tripeptides derived from dietary protein breakdown into epithelial cells. Whereas the transporter appears to be essential to compensate for the reduced amino acid delivery in patients with mutations in amino acid transporter genes, such as in cystinuria or Hartnup disease, its physiological role in overall amino acid absorption is still not known. To assess the quantitative importance of PEPT1 in overall amino acid absorption and metabolism, PEPT1-deficient mice were studied by using brush border membrane vesicles, everted gut sacs, and Ussing chambers, as well as by transcriptome and proteome analysis of intestinal tissue samples. Read More

J Health Popul Nutr 2010 Aug;28(4):413-5

Department of Pediatric Endocrinology and Metabolism, Ataturk University, Erzurum, Turkey.

This report describes an 11-month old girl with Hartnup disease presenting with kwashiorkor and acrodermatitis enteropathica-like skin lesions but free of other clinical findings. This case with kwashiorkor had acrodermatitis enteropathica-like desquamative skin eruption. Since zinc level was in the normal range, investigation for a metabolic disorder was considered, and Hartnup disease was diagnosed. Read More

Pediatr Neurol 2010 May;42(5):369-71

Department of Pediatrics, Genetic and Metabolic Clinic, Children's Hospital, Pusan National University, Gyeongnam, South Korea.

Hartnup disorder is caused by an inborn error of neutral amino acid transport in the kidneys and intestines. It is characterized by pellagra-like rash, ataxia, and psychotic behavior. Elevated urinary neutral amino acids are the first indicator of the disorder. Read More

Nihon Eiseigaku Zasshi 2010 Jan;65(1):37-47

Department of Health and Environmental Sciences, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Genetic dissection of diseases is one of the epoch-making achievements in modern medicine. Positional cloning is a key method to isolate disease-related genes. For positional cloning, there are two conventional methods: family-based studies and case-control studies. Read More

Circ J 2010 Mar 4;74(3):405-10. Epub 2010 Feb 4.

Department of Biological Informatics and Experimental Therapeutics, the Global COE program, Akita University Graduate School of Medicine, Japan.

Angiotensin-converting enzyme 2 (ACE2), a first homolog of ACE, regulates the renin-angiotensin system by counterbalancing ACE activity. Accumulating evidence in recent years has demonstrated a physiological and pathological role of ACE2 in the cardiovascular, renal and respiratory systems. For instance, in the acute respiratory distress syndrome (ARDS), ACE, AngII, and AT1R promote the disease pathogenesis, whereas ACE2 and the AT2R protect from ARDS. Read More

IUBMB Life 2009 Jun;61(6):591-9

School of Biology, College of Medicine, Biology and Environment, Australian National University, Canberra, Australian Capital Territory, Australia.

Hartnup disorder (OMIM 234500) is an autosomal recessive disorder, which was first described in 1956 as an aminoaciduria of neutral amino acids accompanied by a variety of symptoms, such as a photo-sensitive skin-rash and cerebellar ataxia. The disorder is caused by mutations in the neutral amino acid transporter B(0)AT1 (SLC6A19). To date 21 mutations have been identified in more than twenty families. Read More

Int J Dermatol 2009 Apr;48(4):388-92

Department of Dermatology, Peking University First and Third Hospital, Beijing and He Ping Hospital, Chang Zhi Medical College, Changzhi, China.

Background: Hartnup disease is a rare autosomal-recessive abnormality of renal and gastrointestinal neutral amino acid transport associated with neurologic, psychiatric, and dermatologic symptoms. Mutations in the SLC6A19 gene have been proposed to be responsible for the underlying changes in this disorder.

Aim: To investigate a pedigree with Hartnup disorder and to search for the mutation in the SLC6A19 gene in this pedigree. Read More

Gastroenterology 2009 Mar 29;136(3):872-82. Epub 2008 Oct 29.

Institute of Physiology and Zürich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.

Background & Aims: Hartnup amino acid transporter B(0)AT1 (SLC6A19) is the major luminal sodium-dependent neutral amino acid transporter of small intestine and kidney proximal tubule. The expression of B(0)AT1 in kidney was recently shown to depend on its association with collectrin (Tmem27), a protein homologous to the membrane-anchoring domain of angiotensin-converting enzyme (ACE) 2.

Methods: Because collectrin is almost absent from small intestine, we tested the hypothesis that it is ACE2 that interacts with B(0)AT1 in enterocytes. Read More

Clin Exp Dermatol 2009 Mar 6;34(2):178-82. Epub 2008 Nov 6.

Department of Dermatology, Tawam Hospital in affiliation with Johns Hopkins Medicine, Al Ain, UAE.

Exfoliative erythema of malnutrition is a collective term for skin lesions caused by a combination of multiple deficiencies in vitamins, microelements, essential fatty acids and amino acids. We report a 3-year-old Iraqi girl with malnutrition due to coexisting coeliac and Hartnup's disease. On admission to hospital, she presented with kwashiorkor, anaemia, hepatitis and hypoalbuminia. Read More

BMC Psychiatry 2008 Jul 18;8:58. Epub 2008 Jul 18.

Division of Human Molecular Genetics, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka 812-8582, Japan.

Background: Based on the glutamatergic dysfunction hypothesis for schizophrenia pathogenesis, we have been performing systematic association studies of schizophrenia with the genes involved in glutametergic transmission. We report here association studies of schizophrenia with SLC1A4, SLC1A5 encoding neutral amino acid transporters ASCT1, ASCT2, and SLC6A5, SLC6A9 encoding glycine transporters GLYT2, GLYT1, respectively.

Methods: We initially tested the association of 21 single nucleotide polymorphisms (SNPs) distributed in the four gene regions with schizophrenia using 100 Japanese cases-control pairs and examined allele, genotype and haplotype association with schizophrenia. Read More

Hum Mutat 2008 Oct;29(10):1217-21

Medical Genetics Research Unit, Australian National University (ANU) Medical School, Canberra, Australian Capital Territory (ACT), Australia.

Hartnup disorder is an autosomal recessive impairment of amino acid transport in kidney and intestine. Mutations in SLC6A19 have been shown to cosegregate with the disease in the predicted recessive manner; however, in two previous studies (Seow et al., Nat Genet 2004;36:1003-1007; Kleta et al. Read More

FASEB J 2008 Aug 18;22(8):2880-7. Epub 2008 Apr 18.

School of Biochemistry and Molecular Biology, Australian National University, Linnaeus Way 41, Canberra, ACT 0200, Australia.

Protein absorption in the intestine is mediated by proteases and brush-border peptidases together with peptide and amino acid transporters. Neutral amino acids are generated by a variety of aminopeptidases and carboxypeptidases and are subsequently taken up by the amino acid transporter B(0)AT1 (SLC6A19), which is mutated in Hartnup disorder. Coexpression of B(0)AT1 together with the brush-border carboxypeptidase angiotensin-converting enzyme 2 (ACE2) in Xenopus laevis oocytes led to a dramatic increase of transporter expression at the oocyte surface. Read More

Physiology (Bethesda) 2008 Apr;23:95-103

School of Biochemistry and Molecular Biology, Australian National University, Canberra, Australia.

Absorption of amino acids in kidney and intestine involves a variety of transporters for different groups of amino acids. This is illustrated by inherited disorders of amino acid absorption, such as Hartnup disorder, cystinuria, iminoglycinuria, dicarboxylic aminoaciduria, and lysinuric protein intolerance, affecting separate groups of amino acids. Recent advances in the molecular identification of apical neutral amino acid transporters has shed a light on the molecular basis of Hartnup disorder and iminoglycinuria. Read More

Indian J Dermatol 2008 Jan;53(1):31-2

Department of Pediatrics, Clinical Epidemiology Unit, Indira Gandhi Government Medical College, Nagpur, India.

A 10 year old girl presented with clinical signs and symptoms of the triad of niacin deficiency namely skin eruptions, ataxia, mental changes and diarrhea. Although this deficiency could be nutritional where maize is a staple diet, this patient had neutral aminoaciduria which indicated a defective transport of neutral amino acid transporter in the kidneys and intestine resulting in failure of transport of tryptophan and other neutral (ie, monoaminomonocarboxylic) alpha-amino acids in the small intestine and the renal tubules. Read More

J Inherit Metab Dis 2007 Aug 14;30(4):515-21. Epub 2007 Jun 14.

Service of Genetics, Department of Pediatrics, Faculty of Medicine and Health Sciences, Université de Sherbrooke, 3001, 12th Avenue North, Sherbrooke, QC, Canada, J1H 5N4.

The Quebec Mass Urinary Screening Programme, initiated in 1971, has resulted in the screening of more than 2,500,000 newborns in the province of Quebec for 25 inherited Mendelian disorders divided into two groups. The first group concerns urea cycle disorders (citrullinaemia, hyperargininaemia, argininosuccinic aciduria), ketotic hyperglycinaemia, and organic acidurias (methylmalonic aciduria, glutaric aciduria type I, etc.); the second group relates to disorders of amino acid metabolism (cystathioninuria, prolidase deficiency, etc. Read More

Ann Hum Genet 2007 Nov 7;71(Pt 6):755-61. Epub 2007 Jun 7.

Medical Genetics Research Unit, ANU Medical School, Canberra, Australia.

Hartnup disorder is an aminoaciduria that results from mutations in the recently described gene SLC6A19 on chromosome 5p15.33. The disease is inherited in a simple recessive manner and ten different mutations have been described to date. Read More

Nucl Recept Signal 2007 Mar 9;5:e001. Epub 2007 Mar 9.

School of Medical Sciences, IMS Building, University of Aberdeen, Foresterhill, Aberdeen, Scotland, UK.

Steroid hormones are a diverse class of structurally related molecules, derived from cholesterol, that include androgens, estrogens, progesterone and corticosteroids. They represent an important group of physiologically active signalling molecules that bind intracellular receptor proteins and regulate genes involved in developmental, reproductive and metabolic processes. The receptor proteins share structurally and functionally related ligand binding and DNA-binding domains, but possess distinct N-terminal domains (NTD) of unique length and amino acids sequence. Read More

J Biol Chem 2007 May 5;282(18):13754-8. Epub 2007 Mar 5.

Department of Medicine, University of Chicago, Chicago, Illinois 60637, USA.

The insulin receptor is a homodimer composed of two alphabeta half receptors. Scanning mutagenesis studies have identified key residues important for insulin binding in the L1 domain (amino acids 1-150) and C-terminal region (amino acids 704-719) of the alpha subunit. However, it has not been shown whether insulin interacts with these two sites within the same alpha chain or whether it cross-links a site from each alpha subunit in the dimer to achieve high affinity binding. Read More

Fukuoka Igaku Zasshi 2006 Nov;97(11):322-50

Department of Pediatrics Fukuoka Red Cross Hospital, Fukuoka, Japan.

Multiple cases with various types of pediatric malabsorption syndromes were evaluated. The clinical manifestations, laboratory findings, pathophysiology, and histopathological descriptions of each patient were analyzed in an effort to clear the pathogenesis of the malabsorption syndromes and the treatments were undertaken. The cases studied, included one patient with cystic fibrosis, two with lactose intolerance with lactosuria (Durand type), one with primary intestinal lymphangiectasia, two with familial hypobetalipoproteinemia, one with Hartnup disease, one with congenital chroride diarrhea, one with acrodermatitis enteropathica, one with intestinal nodular lymphoid hyperplasia (NLH), five with intractable diarrhea of early infancy and four with glycogenosis type Ia. Read More

Am J Physiol Renal Physiol 2007 Feb 19;292(2):F533-44. Epub 2006 Sep 19.

Dept. of Medicine, Duke University, Durham, NC, USA.

Defects in renal proximal tubule transport manifest in a number of human diseases. Although variable in clinical presentation, disorders such as Hartnup disease, Dent's disease, and Fanconi syndrome are characterized by wasting of solutes commonly recovered by the proximal tubule. One common feature of these disorders is aminoaciduria. Read More

Pediatr Dermatol 2006 May-Jun;23(3):262-5

Department of Dermatology, Inönü University, Malatya, Faculty of Medicine, Atatürk University, Erzurum, Turkey.

Acrodermatitis enteropathica-like eruptions, not related to zinc deficiency, have been rarely reported in some metabolic disorders. Reported patients usually had low levels of essential amino acids, particularly isoleucine. Here we report a girl who first presented with an acrodermatitis enteropathica-like eruption and eventually had the diagnosis of Hartnup disease with a normal isoleucine level. Read More

Nihon Rinsho 2006 Feb;64 Suppl 2:541-4

Department of Pediatrics, Tohoku University, Graduate School of Medicine.

Nihon Rinsho 2006 Feb;64 Suppl 2:522-7

Department of Nephrology and Hypertension, Saitama Medical Center, Saitama Medical School.

Ann Dermatol Venereol 2005 Aug-Sep;132(8-9 Pt 1):726

Trends Pharmacol Sci 2005 Feb;26(2):53-5

Membrane Biology Laboratory, Medical and Research Services, VAGLA Healthcare System and UCLA School of Medicine, Los Angeles, CA 90073, USA.

Hartnup disorder is an autosomal recessive disease that can be associated with neurological, psychiatric and dermatological abnormalities or be asymptomatic. Excessive intestinal and urinary loss of neutral amino acids is an essential feature of this disorder, which had been presumed to be due to hereditary abnormalities in an apical membrane-situated amino acid transporter. As anticipated, recently, mutations in the cytoplasmic and transmembrane domains of SLC6A19, the recently cloned neutral amino acid transporter, were detected in members of families with Hartnup disorder. Read More

Biochem Soc Trans 2005 Feb;33(Pt 1):233-6

School of Biochemistry and Molecular Biology, Australian National University, Canberra, ACT 0200, Australia.

Hartnup disorder is an autosomal recessive abnormality of renal and gastrointestinal neutral amino acid transport. A corresponding transport activity has been characterized in kidney and intestinal cells and named system B(0). The failure to resorb amino acids in this disorder is thought to be compensated by a protein-rich diet. Read More

Nat Genet 2004 Sep 1;36(9):1003-7. Epub 2004 Aug 1.

Gene Therapy, Centenary Institute of Cancer Medicine & Cell Biology, University of Sydney, NSW 2042, Australia.

Hartnup disorder (OMIM 234500) is an autosomal recessive abnormality of renal and gastrointestinal neutral amino acid transport noted for its clinical variability. We localized a gene causing Hartnup disorder to chromosome 5p15.33 and cloned a new gene, SLC6A19, in this region. Read More

Nat Genet 2004 Sep 1;36(9):999-1002. Epub 2004 Aug 1.

Medical Genetics Branch, 10 Center Drive, MSC 1851, Building 10, Room 10C-107, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland, USA.

Hartnup disorder, an autosomal recessive defect named after an English family described in 1956 (ref. 1), results from impaired transport of neutral amino acids across epithelial cells in renal proximal tubules and intestinal mucosa. Symptoms include transient manifestations of pellagra (rashes), cerebellar ataxia and psychosis. Read More

Adv Exp Med Biol 2003 ;527:325-35

Clinic for Neurology and Psychiatry for Children and Young People Dr Subotica 6a. 11000 Belgrade, Yugoslavia.

Two cases of Hartnup disease were diagnosed in a five member family. A changeable polymorph and severe clinical features of a 16 year old girl was described. Total plasma amino acids value was significantly decreased in the girl compared to the sum of plasma amino acids value in the brother, mother, father and to the summed maximal values of normal range. Read More

J Endovasc Ther 2004 Jun;11(3):348-50

Department of Maxillo-Facial Surgery, Charité, Humboldt University, Berlin, Germany.

Purpose: To report the endovascular treatment of a spontaneous scalp arteriovenous fistula (AVF) in a child with Hartnup disease.

Case Report: A 6-year-old girl with Hartnup disease presented with recurrent attacks of intense, migraine-like, right-sided headache; a tender, pulsatile small mass was observed in the scalp. Selective digital subtraction angiography revealed a high-flow scalp AVF fed by the frontal branch of the right superficial temporal artery draining via the scalp veins. Read More

J Biol Chem 2004 Jun 25;279(23):24467-76. Epub 2004 Mar 25.

School of Biochemistry and Molecular Biology, Australian National University, Canberra ACT 0200, Australia.

Resorption of amino acids in kidney and intestine is mediated by transporters, which prefer groups of amino acids with similar physico-chemical properties. It is generally assumed that most neutral amino acids are transported across the apical membrane of epithelial cells by system B(0). Here we have characterized a novel member of the Na(+)-dependent neurotransmitter transporter family (B(0)AT1) isolated from mouse kidney, which shows all properties of system B(0). Read More

J Inherit Metab Dis 2002 Oct;25(6):437-48

Gene Therapy Research Unit, Centenary Institute of Cancer Medicine and Cell Biology, NSW, Australia.

Hartnup disorder is an inborn error of renal and gastrointestinal neutral amino acid transport. The cloning and functional characterization of the 'system B0' neutral amino acid transporter SLC1A5 led to it being proposed as a candidate gene for Hartnup disorder. Linkage analysis performed at 19q13. Read More

Phys Med Biol 2002 Jul;47(13):N185-90

Academic Unit of Radiology, University of Sheffield, Royal Hallamshire Hospital, UK.

Hyperpolarized noble gas MRI shows promise in the functional imaging of the pulmonary air spaces. The production of hyperpolarized (HP) gas requires specialized laser optical pumping apparatus, which is not likely to be home built in the majority of clinical MRI radiology centres. There are two routes through which HP gas will be made available to hospitals for clinical use: either the apparatus will be installed locally at a considerable expense to the centre, or a central facility will produce the gas and then deliver it to remote MRI sites as and when required. Read More

Ryoikibetsu Shokogun Shirizu 2001 (33):788-90

Department of Pediatrics, Nihon University Surugadai Hospital.

Biochem Biophys Res Commun 2001 Jun;284(2):255-60

Department of Health and Environmental Sciences, Kyoto University School of Public Health, Kyoto, 606-8501, Japan.

Hartnup disorder is an autosomal recessive phenotype involving a transporter for monoamino-monocarboxylic acids. Genetic analysis of the mouse model mapped its locus to human chromosome 11q13 (8). We report here the results of linkage analysis in two Japanese first cousin-marriage families. Read More

Usp Fiziol Nauk 2000 Oct-Dec;31(4):24-37

I. P. Pavlov Institute of Physiology, RAS, St. Petersburg.

The review is mainly devoted to the development of ideas about absorption, or transport, of basic nutrients in the small intestine in humans and higher animal. The absorption processes have been characterized on the example of such substances, vital for organism, as carbohydrates and proteins. The review considers a molecular structure of transporters--protein molecules, which take part in a transfer of the products of lumenal and membrane digestion of carbohydrates (glucose, galactose, fructose) and proteins (amino acids, oligopeptides) across the enterocyte membranes. Read More

Srp Arh Celok Lek 2000 Mar-Apr;128(3-4):97-103

Department of Neurology and Psychiatry of Children and Young People, Belgrade.

Introduction: The Hartnup mutation affects the amino acid transport system of the intestine and kidney used by a large group of neutral amino acids (monoamino-monocarboxylic acids) resulting in a characteristic pattern of neutral aminoaciduria [2, 5, 6].

Methods And Patients: In this research clinical and neurological methods and a great number of laboratory tests were used. Patient 1. Read More

Nihon Rinsho 1999 Oct;57(10):2211-7

Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University.

Nicotinic acid and nicotinamide are called niacin. They are the antipellagra vitamin essential to many animals for growth and health. In human being, niacin is believed necessary together with other vitamins for the prevention and cure of pellagra. Read More

Nihon Rinsho 1999 Aug;57 Suppl:136-8

Jikei University School of Medicine.

J Chromatogr B Biomed Sci Appl 1999 Aug;731(1):141-7

Division of Human Genetics, Medical Research Institute, Kanazawa Medical University, Ishikawa, Japan.

Gas chromatographic-mass spectrometric (GC-MS) techniques for urinary organic acid profiling have been applied to high-risk screening for a wide range of diseases, mainly for inborn errors of metabolism (IEM), rather than to low-risk screening or mass screening. Using a simplified procedure with urease-pretreatment and the GC-MS technique, which allows simultaneous determination of organic acids, amino acids, sugars and sugar acids, we performed a pilot study of the application of this procedure to neonatal urine screening for 22 IEM. Out of 16,246 newborns screened, 11 cases of metabolic disorders were chemically diagnosed: two each of methylmalonic aciduria and glyceroluria, four of cystinuria, and one each of Hartnup disease, citrullinemia and alpha-aminoadipic aciduria/alpha-ketoadipic aciduria. Read More

Ryoikibetsu Shokogun Shirizu 1998 (19 Pt 2):565-8

Faculty of Human Life Sciences, Notre Dame Seishin University.

Mamm Genome 1997 Feb;8(2):102-7

McArdle Laboratory for Cancer Research, University of Wisconsin, Madison 53706, USA.

The mutant mouse strain HPH2 (hyperphenylalaninemia) was isolated after N-ethyl-N-nitrosourea (ENU) mutagenesis on the basis of delayed plasma clearance of an injected load of phenylalanine. Animals homozygous for the recessive hph2 mutation excrete elevated concentrations of many of the neutral amino acids in the urine, while plasma concentrations of these amino acids are normal. In contrast, mutant homozygotes excrete normal levels of glucose and phosphorus. Read More