ABSTRACT
El síndrome de deficiencia del transportador de glucosa tipo 1 es una enfermedad de causa genética, que involucra el gen SLC2A1. En general, se presenta durante los primeros años de vida con retraso en la adquisición de pautas madurativas, epilepsia farmacorresistente y desórdenes del movimiento. La clínica y la disminución de glucosa en líquido cefalorraquídeo permiten sospechar el diagnóstico, el cual debe ser confirmado mediante el estudio molecular del gen SLC2A1. Debido a que se trata de una enfermedad poco frecuente y de expresión clínica variable, el diagnóstico precoz suele representar un desafío para los equipos de salud. Este es importante, ya que la implementación de la terapia cetogénica logra controlar las manifestaciones clínicas y mejora el pronóstico a largo plazo. Presentamos una revisión sobre el déficit del transportador de glucosa tipo 1, que abarca sus características clínicas, bioquímicas, moleculares y terapéuticas.
Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid, and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.
Subject(s)
Humans , Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/genetics , Carbohydrate Metabolism, Inborn Errors/therapy , Monosaccharide Transport Proteins/genetics , Epilepsy/diagnosis , Epilepsy/genetics , MutationABSTRACT
Glucose transporter type 1 deficiency with a typical onset is a genetic disorder associated with the SLC2A1 gene. Usually appears during the first years of life with severe developmental delay, drugresistant epilepsy, and movement disorders. Diagnosis is suspected based on clinical manifestations and a low glucose level in cerebrospinal fluid,and should be confirmed by the molecular genetic study of the SLC2A1 gene. As it is a rare disease with variable clinical expression, early diagnosis is often challenging for the healthcare team. Nevertheless, this is important because early implementation of ketogenic therapy will lead to control of the clinical manifestations and a better long-term prognosis. Here we review the glucose transporter type 1 deficiency syndrome focusing on its clinical, biochemical, molecular, and therapeutic characteristics.
El síndrome de deficiencia del transportador de glucosa tipo 1 es una enfermedad de causa genética, que involucra el gen SLC2A1. En general, se presenta durante los primeros años de vida con retraso en la adquisición de pautas madurativas, epilepsia farmacorresistente y desórdenes del movimiento. La clínica y la disminución de glucosa en líquido cefalorraquídeo permiten sospechar el diagnóstico, el cual debe ser confirmado mediante el estudio molecular del gen SLC2A1. Debido a que se trata de una enfermedad poco frecuente y de expresión clínica variable, el diagnóstico precoz suele representar un desafío para los equipos de salud. Este es importante, ya que la implementación de la terapia cetogénica logra controlar las manifestaciones clínicas y mejora el pronóstico a largo plazo. Presentamos una revisión sobre el déficit del transportador de glucosa tipo 1, que abarca sus características clínicas, bioquímicas, moleculares y terapéuticas.
Subject(s)
Carbohydrate Metabolism, Inborn Errors , Humans , Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/genetics , Carbohydrate Metabolism, Inborn Errors/therapy , Epilepsy/diagnosis , Epilepsy/genetics , Monosaccharide Transport Proteins/genetics , MutationABSTRACT
Glucose transporter type 1 deficiency syndrome is a rare pediatric neurometabolic disorder. There are two phenotypes: the classical phenotype (85%) and the non-classic (15%). Both phenotypes are associated with hypoglycorrhachia. Multiple mutations are described in the SCL2A1 gene. The treatment is the ketogenic diet. We report a case of a four-year-old male patient who started with hemichorea and hemidystonia and was medicated with drugs for seizures without clinical response, that's why his parents made another pediatric consultation at his six-year-old. With the suggestive clinical findings of glucose transporter type 1 deficiency syndrome the lumbar puncture was made confirming the diagnosis. Immediately after starting the ketogenic diet the patient stopped making abnormal movements up to the moment when he is fourteen years old, eight years after.
El síndrome de deficiencia del transportador de glucosa cerebral de tipo 1 es una enfermedad neurometabólica rara en pediatría. Existe un fenotípico clásico (85 %) y otro no clásico (15 %). Ambos fenotipos se asocian con hipoglucorraquia. Se identifican múltiples mutaciones en el gen SLC2A1. El tratamiento es la terapia cetogénica. Se presenta un varón que comenzó a los cuatro años con hemicorea y hemidistonía medicado con anticonvulsivantes sin respuesta clínica, por lo que consultó nuevamente a los seis años. Con sospecha diagnóstica de síndrome de déficit de glut-1 atípico se realizó punción lumbar; el diagnóstico se confirmó por la presencia de hipoglucorraquia. Inmediatamente después de iniciar la dieta cetogénica, el paciente no presentó más movimientos anormales durante los siguientes 8 años hasta la actualidad, ya cumplidos los 14 años.
Subject(s)
Carbohydrate Metabolism, Inborn Errors , Diet, Ketogenic , Carbohydrate Metabolism, Inborn Errors/complications , Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/genetics , Glucose Transporter Type 1 , Humans , Male , Monosaccharide Transport Proteins/deficiency , Monosaccharide Transport Proteins/geneticsABSTRACT
El síndrome de deficiencia del transportador de glucosa cerebral de tipo 1 es una enfermedad neurometabólica rara en pediatría. Existe un fenotípico clásico (85 %) y otro no clásico (15 %). Ambos fenotipos se asocian con hipoglucorraquia. Se identifican múltiples mutaciones en el gen SLC2A1. El tratamiento es la terapia cetogénica. Se presenta un varón que comenzó a los cuatro años con hemicorea y hemidistonía medicado con anticonvulsivantes sin respuesta clínica, por lo que consultó nuevamente a los seis años. Con sospecha diagnóstica de síndrome de déficit de glut-1 atípico se realizó punción lumbar; el diagnóstico se confirmó por la presencia de hipoglucorraquia. Inmediatamente después de iniciar la dieta cetogénica, el paciente no presentó más movimientos anormales durante los siguientes 8 años hasta la actualidad, ya cumplidos los 14 años.
Glucose transporter type 1 deficiency syndrome is a rare pediatric neurometabolic disorder. There are two phenotypes: the classical phenotype (85%) and the non-classic (15%). Both phenotypes are associated with hypoglycorrhachia. Multiple mutations are described in the SCL2A1 gene. The treatment is the ketogenic diet. We report a case of a four-year-old male patient who started with hemichorea and hemidystonia and was medicated with drugs for seizures without clinical response, that's why his parents made another pediatric consultation at his six-year-old. With the suggestive clinical findings of glucose transporter type 1 deficiency syndrome the lumbar puncture was made confirming the diagnosis. Immediately after starting the ketogenic diet the patient stopped making abnormal movements up to the moment when he is fourteen years old, eight years after.
Subject(s)
Humans , Male , Adolescent , Carbohydrate Metabolism, Inborn Errors/complications , Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/genetics , Diet, Ketogenic , Monosaccharide Transport Proteins/deficiency , Monosaccharide Transport Proteins/genetics , Glucose Transporter Type 1ABSTRACT
INTRODUCTION: Glucose Transporter Type 1 Deficiency Syndrome (GLUT1-DS) is caused by the SLC2A1 gene muta tion, which encodes the glucose transporter proteins to the brain Neurological manifestations occur in three main domains: seizures, abnormal movements, and cognitive disorders. The diagnosis is presumed upon the finding of low CSF glucose and confirmed by the gene molecular analysis. Ac curate diagnosis is important because it has a specific treatment, which is ketogenic diet. OBJECTIVE: To analyze two SD-GLUT1 pediatric patients with unusual phenotype. CLINICAL CASE: We present the case of two siblings who presented absence seizures and a paroxysmal movement disorder. Both patients were studied, finding low CSF glucose. The diagnosis of GLUT1-DS was confirmed with molecular analysis. Specific treatment with ketogenic diet achieved good response in both cases. Con clusions: We present their peculiar clinical characteristics that allowed us to suspect this wide phe notypic spectrum. Correct and timely diagnosis and treatment can significantly improve the quality of life of those affected.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/diagnosis , Monosaccharide Transport Proteins/deficiency , Movement Disorders/etiology , Phenotype , Seizures/etiology , Carbohydrate Metabolism, Inborn Errors/complications , Child, Preschool , Female , Humans , MaleABSTRACT
Resumen: Introducción: La deficiencia del transportador de glucosa tipo 1 constituye un síndrome (SD-GLUT1), provocado por la mutación del gen SLC2A1, que codifica la proteína transportadora de glucosa al encéfalo. Las manifestaciones neurológicas se dan en tres dominios principales: crisis epilépticas, movimientos anormales y alteraciones cognitivas. El diagnóstico se presume ante el hallazgo de hipoglucorraquia y se confirma mediante el análisis molecular del gen. La importancia de precisarlo radica en que tiene tratamiento específico, la dieta cetogénica. Objetivo: Analizar dos casos clínicos de SD-GLUT1 de presentación atípica, destacando la variabilidad del fenotipo. Caso Clínico: Presentamos el caso de dos hermanos cuyas manifestaciones fueron crisis epilépticas de tipo ausencias típicas, y un trastorno paroxístico del movimiento. Los pacientes fueron estudiados encontrándose hipoglucorraquia en ambos y se confirmó diagnóstico de SD-GLUT1 con estudio molecular. El tratamiento específico con dieta cetogénica logró buena respuesta. Conclusiones: Exponemos sus características clínicas peculiares que nos permitieron sospechar este cuadro, de espectro fenotípico amplio, cuyo diagnós tico y tratamiento, correcto y oportuno, puede mejorar significativamente la calidad de vida de los afectados.
Abstract: Introduction: Glucose Transporter Type 1 Deficiency Syndrome (GLUT1-DS) is caused by the SLC2A1 gene muta tion, which encodes the glucose transporter proteins to the brain Neurological manifestations occur in three main domains: seizures, abnormal movements, and cognitive disorders. The diagnosis is presumed upon the finding of low CSF glucose and confirmed by the gene molecular analysis. Ac curate diagnosis is important because it has a specific treatment, which is ketogenic diet. Objective: To analyze two SD-GLUT1 pediatric patients with unusual phenotype. Clinical Case: We present the case of two siblings who presented absence seizures and a paroxysmal movement disorder. Both patients were studied, finding low CSF glucose. The diagnosis of GLUT1-DS was confirmed with molecular analysis. Specific treatment with ketogenic diet achieved good response in both cases. Con clusions: We present their peculiar clinical characteristics that allowed us to suspect this wide phe notypic spectrum. Correct and timely diagnosis and treatment can significantly improve the quality of life of those affected.
Subject(s)
Humans , Male , Female , Child, Preschool , Phenotype , Seizures/etiology , Monosaccharide Transport Proteins/deficiency , Carbohydrate Metabolism, Inborn Errors/diagnosis , Movement Disorders/etiology , Carbohydrate Metabolism, Inborn Errors/complicationsABSTRACT
TITLE: Sindrome de deficiencia de GLUT-1.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/diagnosis , Monosaccharide Transport Proteins/deficiency , Ataxia/etiology , Carbohydrate Metabolism, Inborn Errors/complications , Carbohydrate Metabolism, Inborn Errors/diet therapy , Carbohydrate Metabolism, Inborn Errors/genetics , Child , Chronic Disease , Delayed Diagnosis , Developmental Disabilities/etiology , Diarrhea/etiology , Diet, Ketogenic , Drug Resistant Epilepsy/etiology , Electroencephalography , Genes, Dominant , Glucose Transporter Type 1/deficiency , Glucose Transporter Type 1/genetics , Heterozygote , Humans , Male , Monosaccharide Transport Proteins/geneticsABSTRACT
OBJECTIVES: To evaluate the role of next generation sequencing in genetic diagnosis of pediatric patients with persistent hypoglycemia. STUDY DESIGN: Sixty-four patients investigated through an extensive workup were divided in 3 diagnostic classes based on the likelihood of a genetic diagnosis: (1) single candidate gene (9/64); (2) multiple candidate genes (43/64); and (3) no candidate gene (12/64). Subsequently, patients were tested through a custom gene panel of 65 targeted genes, which included 5 disease categories: (1) hyperinsulinemic hypoglycemia, (2) fatty acid-oxidation defects and ketogenesis defects, (3) ketolysis defects, (4) glycogen storage diseases and other disorders of carbohydrate metabolism, and (5) mitochondrial disorders. Molecular data were compared with clinical and biochemical data. RESULTS: A proven diagnosis was obtained in 78% of patients with suspicion for a single candidate gene, in 49% with multiple candidate genes, and in 33% with no candidate gene. The diagnostic yield was 48% for hyperinsulinemic hypoglycemia, 66% per fatty acid-oxidation and ketogenesis defects, 59% for glycogen storage diseases and other carbohydrate disorders, and 67% for mitochondrial disorders. CONCLUSIONS: This approach provided a diagnosis in ~50% of patients in whom clinical and laboratory evaluation did not allow identification of a single candidate gene and a diagnosis was established in 33% of patients belonging to the no candidate gene class. Next generation sequencing technique is cost-effective compared with Sanger sequencing of multiple genes and represents a powerful tool for the diagnosis of inborn errors of metabolism presenting with persistent hypoglycemia.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/genetics , Genomics/methods , Hypoglycemia/diagnosis , Hypoglycemia/genetics , Adolescent , Child , Child, Preschool , Chronic Disease , Cohort Studies , DNA Mutational Analysis/methods , Genetic Predisposition to Disease/epidemiology , Gluconeogenesis/physiology , Glycogen Storage Disease/diagnosis , Glycogen Storage Disease/genetics , High-Throughput Nucleotide Sequencing/methods , Humans , Infant , Infant, Newborn , Italy , Male , Mitochondrial Diseases/diagnosis , Mitochondrial Diseases/genetics , Retrospective Studies , Sensitivity and SpecificityABSTRACT
OBJECTIVE: To profile the initial clinical events of glucose transporter 1 deficiency syndrome (Glut1 DS) in order to facilitate the earliest possible diagnosis. STUDY DESIGN: We retrospectively reviewed 133 patients with Glut1 DS from a single institution. Family interviews and medical record reviews identified the first clinical event(s) reported by the caregivers. RESULTS: Average age of the first event was 8.15 ± 11.9 months (range: 0.01-81). Ninety-one patients experienced the first symptom before age 6 months (68%). Thirty-three additional patients (25%) presented before age 2 years. Only 9 patients (7%), reported the first event after age 2 years. Seizures were the most common first event (n = 81, 61%), followed by eye movement abnormalities (n = 51, 38%) and changes in muscle strength and tone (n = 30, 22%). Eye movement abnormalities, lower cerebrospinal fluid glucose values, and lower Columbia Neurological Scores correlated with earlier onset of the first event (r: -0.17, 0.22, and 0.25 respectively, P < .05). There was no correlation with age of first event and red blood cell glucose uptake or mutation type. CONCLUSIONS: Glut1 DS is a treatable cause of infantile onset encephalopathy. Health care providers should recognize the wide spectrum of paroxysmal events that herald the clinical onset of Glut1 DS in early infancy to facilitate prompt diagnosis, immediate treatment, and improved long-term outcome.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/diagnosis , Glucose Transporter Type 1/deficiency , Age of Onset , Anticonvulsants/therapeutic use , Brain/growth & development , Carbohydrate Metabolism, Inborn Errors/therapy , Caregivers , Child , Child, Preschool , Diet, Ketogenic , Early Medical Intervention , Epilepsy/diagnosis , Eye Movements , Female , Humans , Infant , Infant, Newborn , Male , Medical Records , Pediatrics/methods , Retrospective Studies , Seizures/diagnosis , Seizures/drug therapyABSTRACT
In some cases Neu-Laxova syndrome (NLS) is linked to serine deficiency due to mutations in the phosphoglycerate dehydrogenase (PHGDH) gene. We describe the prenatal and postnatal findings in a fetus with one of the most severe NLS phenotypes described so far, caused by a homozygous nonsense mutation of PHGDH. Serial ultrasound (US) and pre- and postnatal magnetic resonance imaging (MRI) evaluations were performed. Prenatally, serial US evaluations suggested symmetric growth restriction, microcephaly, hypoplasia of the cerebellar vermis, micrognathia, hydrops, shortened limbs, arthrogryposis, and talipes equinovarus. The prenatal MRI confirmed these findings prompting a diagnosis of NLS. After birth, radiological imaging did not detect any gross bone abnormalities. DNA was extracted from fetal and parental peripheral blood, all coding exons of PHGDH were PCR-amplified and subjected to Sanger sequencing. Sequencing of PHGDH identified a homozygous premature stop codon mutation (c.1297C>T; p.Gln433*) in fetal DNA, both parents (first-cousins) being heterozygotes. Based on previous associations of mutations in this gene with a milder NLS phenotype, as well as cases of serine deficiency, these observations lend further support to a genotype-phenotype correlation between the degree of PHGDH inactivation and disease severity.
Subject(s)
Abnormalities, Multiple/genetics , Brain Diseases/genetics , Carbohydrate Metabolism, Inborn Errors/genetics , Codon, Nonsense , Fetal Growth Retardation/genetics , Ichthyosis/genetics , Limb Deformities, Congenital/genetics , Microcephaly/genetics , Phenotype , Phosphoglycerate Dehydrogenase/deficiency , Phosphoglycerate Dehydrogenase/genetics , Psychomotor Disorders/genetics , Seizures/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/pathology , Base Sequence , Brain Diseases/diagnosis , Brain Diseases/pathology , Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/pathology , Consanguinity , Female , Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/pathology , Fetus , Gene Expression , Genes, Lethal , Genetic Variation , Genotype , Homozygote , Humans , Ichthyosis/diagnosis , Ichthyosis/pathology , Infant, Newborn , Limb Deformities, Congenital/diagnosis , Limb Deformities, Congenital/pathology , Male , Microcephaly/diagnosis , Microcephaly/pathology , Molecular Sequence Data , Pedigree , Psychomotor Disorders/diagnosis , Psychomotor Disorders/pathology , Seizures/diagnosis , Seizures/pathology , Sequence Analysis, DNA , Severity of Illness Index , Ultrasonography, PrenatalSubject(s)
Carbohydrate Metabolism, Inborn Errors/genetics , Phenotype , Sucrase-Isomaltase Complex/deficiency , Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/therapy , Diarrhea, Infantile/etiology , Diarrhea, Infantile/therapy , Glycoside Hydrolases/administration & dosage , Humans , Infant , Infant Food/adverse effects , Saccharomyces cerevisiae/enzymology , beta-FructofuranosidaseABSTRACT
OBJECTIVE: To describe four infants with protracted diarrhea caused by glucose polymer intolerance resulting from congenital sucrase-isomaltase deficiency. METHODS: The diagnosis of congenital sucrase-isomaltase deficiency was established by mucosal disaccharidase assay. In each case the clinical response to discontinuation of glucose polymer was documented. RESULTS: The median age at the onset of symptoms was 3 weeks (range, 2 to 16 weeks). In three infants the formula had been prescribed for presumed postgastroenteritis diarrhea, and in a fourth it was begun after resection of a short-segment congenital ileal atresia. In each infant watery diarrhea occurred and persisted for many months, and it was assumed that the original gastrointestinal disorder was responsible. In two cases, parenteral nutrition was administered for persistent failure to thrive. Ultimately, investigation revealed the underlying congenital sucrase-isomaltase deficiency, and elimination of glucose polymer from the diet led to immediate recovery in each case. CONCLUSION: Congenital sucrase-isomaltase deficiency should be considered a possible cause of protracted diarrhea in infants receiving glucose polymer-based feedings.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/genetics , Diarrhea, Infantile/etiology , Glucans/adverse effects , Infant Food/adverse effects , Sucrase-Isomaltase Complex/deficiency , Carbohydrate Metabolism, Inborn Errors/diagnosis , Carbohydrate Metabolism, Inborn Errors/enzymology , Diagnosis, Differential , Failure to Thrive/etiology , Female , Humans , Infant , Infant, Newborn , Intestinal Mucosa/enzymology , MaleSubject(s)
Humans , Male , Female , Infant , Carbohydrate Metabolism, Inborn Errors/diagnosis , Dietary Carbohydrates/adverse effects , Carbohydrate Metabolism, Inborn Errors/diet therapy , Food, Formulated/analysis , Lactose Intolerance/diagnosis , Lactose Intolerance/diet therapy , Malabsorption Syndromes/diagnosis , Malabsorption Syndromes/diet therapyABSTRACT
We diagnosed the carbohydrate-deficient glycoprotein syndrome in five children who were seen during their first year of life with failure to thrive, feeding difficulties, psychomotor retardation, hypotonia, esotropia, inverted nipples, lipodystrophy, pericardial effusion, and hepatic dysfunction. Steatosis was observed in liver biopsy specimens, and cerebellar hypoplasia was present on computed tomography. The disorder is characterized by a complex carbohydrate deficiency in certain glycoproteins, notably transferrin, which can be used as a marker of the disease. The carbohydrate-deficient glycoprotein syndrome may be an important and easily identifiable cause of failure to thrive and neurologic dysfunction in infancy. The presence of the disorder in siblings of different gender and the finding of biochemical abnormalities in some unaffected parents suggest an autosomal recessive inheritance.
Subject(s)
Biomarkers/analysis , Carbohydrate Metabolism, Inborn Errors/diagnosis , Glycoproteins/analysis , Psychomotor Disorders/pathology , Transferrin/analogs & derivatives , Transferrin/analysis , Cerebellum/abnormalities , Failure to Thrive , Female , Humans , Infant , Male , SyndromeABSTRACT
Complex carbohydrate intolerance occurred in three of 105 patients with protracted diarrhea of infancy. Nosocomial gastroenteritis complicated a primary disorder of carbohydrate absorption (primary glucose galactose malabsorption, two; primary sucrase isomaltase deficiency, one) in all patients. Their course was characterized by protracted diarrhea, variable degrees of villus atrophy on intestinal biopsy tissue, and negative caloric balance requiring intravenous alimentation for periods varying from 6 to 16 weeks. Dietary management required rigid exclusion of all offending carbohydrates from the diet. Delay in the diagnosis of primary carbohydrate intolerance varied from 2 weeks to 6 months. Complex carbohydrate intolerance may be more common than has been reported, and should be considered in all infants with protracted diarrhea of infancy when there is persistent carbohydrate intolerance.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/diagnosis , Galactose/metabolism , Glucose/metabolism , Malabsorption Syndromes/diagnosis , Sucrose/metabolism , Carbohydrate Metabolism, Inborn Errors/diet therapy , Carbohydrate Metabolism, Inborn Errors/pathology , Diarrhea/etiology , Humans , Infant, Newborn , Intestines/pathology , Malabsorption Syndromes/diet therapy , Malabsorption Syndromes/pathology , Male , Sucrase-Isomaltase Complex/deficiencyABSTRACT
Salla disease is an autosomal recessive lysosomal storage disorder; increased amounts of free sialic acid (N-acetylneuraminic acid) are found in urine and tissues. The disease causes severe psychomotor retardation, with onset by 1 year of age, but the patients have an apparently normal life-span. This paper describes the clinical features of Salla disease in six infants and young children and provides the background for laboratory diagnosis by thin-layer chromatography or spectrophotometric determination of sialic acid in urine.
Subject(s)
Carbohydrate Metabolism, Inborn Errors/diagnosis , Sialic Acids/metabolism , Age Factors , Carbohydrate Metabolism, Inborn Errors/physiopathology , Carbohydrate Metabolism, Inborn Errors/urine , Child , Child, Preschool , Chromatography, Thin Layer , Female , Finland , Humans , Hydrolases/metabolism , Infant , Lysosomes/enzymology , Male , Sialic Acids/urine , Skin/ultrastructureABSTRACT
Neonatal ascites is usually attributed to hematologic, genitourinary, gastrointestinal tract, or congenital heart disease. When these lesions have been excluded, metabolic storage disorders should be considered in the differential diagnosis. We report eight cases of neonatal ascites associated with different types of lysosomal storage disease: infantile sialidosis, Salla disease, GM1 gangliosidosis, and Gaucher disease. In each case there was a history of sibling of perinatal death resulting from the disease. In three cases the diagnosis of ascites was made in utero by ultrasound examination. These diseases are characterized by excretion in the fetal urine of abnormal catabolic products or by measurement of decreased activity of specific lysosomal hydrolases in cultured amniocytes. Thin-layer chromatography of the oligosaccharides in amniotic fluid may be indicated when a diagnosis of persistent fetal ascites has been established.
Subject(s)
Ascites/congenital , Carbohydrate Metabolism, Inborn Errors/diagnosis , Sialic Acids/metabolism , Adult , Amniotic Fluid/analysis , Chromatography, Thin Layer , Female , G(M3) Ganglioside/metabolism , Gangliosidoses/diagnosis , Gaucher Disease/diagnosis , Humans , Infant, Newborn , Liver/pathology , Mucolipidoses/diagnosis , Oligosaccharides/analysis , Pregnancy , Prenatal DiagnosisABSTRACT
Results of screening tests for the detection of inborn errors of metabolism in 1,117 consecutive patients are reported in this work; patients came for a second consultation to the Departamento de Genética, Centro Médico de Occidente, IMSS. Simple qualitative test were made that revealed the presence of abnormal metabolites (amino-acids, sugars, organic acids and mucopolysaccharides) in urine and blood as well as identification tests for variant proteins. Results were positive in 138 patients and test for confirmation and/or specificity were made in all patients; in 35 the following diagnosis and incidence were established: classic galactosemia, 2; glucose-6-phosphate dehydrogenase deficiency, 20; essential pentosuria, 1; hyperphenylalaninemia, 5; blue diaper syndrome, 1; cistinuria 1, and type 1 mucopolysaccharidosis, 5.