ABSTRACT
A 12-year-old child presented with asymptomatic, noninflammatory, generalized peeling of the skin since early childhood. He was diagnosed as having type A continual peeling skin syndrome. Associated increased excretion of cystine and histidine in the urine has hitherto not been reported.
Subject(s)
Renal Aminoacidurias/complications , Skin Diseases/complications , Child , Consanguinity , Cystinuria/complications , Epithelium/pathology , Histidine/urine , Humans , MaleABSTRACT
OBJECTIVE: A prenatal diagnosis of the fetus for a mother of two previously deceased infants who died from the recently described autosomal recessive disease (OMIM 603358). The infants presented with intrauterine growth retardation, aminoaciduria, cholestasis, iron overload, severe lactic acidosis, and early death (GRACILE syndrome). STUDY DESIGN: DNA was extracted from the fibroblasts and tissue samples of the deceased infants, parental leukocytes, and from a chorion villus biopsy in the next pregnancy. Haplotypes were determined using the relevant markers flanking the disease-associated region of chromosome 2. RESULTS: Both deceased infants were homozygous for the four critical markers. The fetal haploptypes were identical to those of the siblings and the pregnancy was terminated. The iron content of the fetal liver was increased (5000 microg/g) compared with the controls, with a marked iron accumulation in the Kupffer cells. CONCLUSIONS: Antenatal diagnosis can be performed based on linkage analysis in families with at least one affected child because the disease locus has been assigned to a restricted chromosomal region. Typical histological abnormalities may be present in early fetal life.
Subject(s)
Fetal Growth Retardation/diagnosis , Fetal Growth Retardation/genetics , Prenatal Diagnosis , White People/genetics , Abortion, Induced , Acidosis, Lactic/complications , Cholestasis/complications , Chorionic Villi Sampling , Female , Fetal Growth Retardation/complications , Finland , Humans , Infant, Newborn , Iron Overload/complications , Liver/pathology , Male , Pedigree , Pregnancy , Renal Aminoacidurias/complications , SyndromeABSTRACT
Autopsy study of 17 newborn infants with lethal autosomal recessive disease presenting as growth retardation with lactic acidosis, Fanconi aminoaciduria, and hepatic hemosiderosis is reported. The patients succumbed between day 1 and 4 months of life; 9 patients died within the first month. All patients showed severe pathologic changes of liver with cholestasis in all livers. Extensive accumulation of stainable iron of the hepatocytes was present in 9/17 autopsy tissues and in two biopsy specimens. Moderate to abundant iron storage in the Kupffer cells was seen in all liver specimens. The amount of hepatocytic iron was high in livers up to 1 month of age and decreased thereafter. The general features and liver findings of this disorder suggest the name Growth Retardation Aminoaciduria Cholestasis Iron Overload, Lactacidosis and Early Death (GRACILE, OMIM 603358). Calcified concrements were seen in the medulla of 13/16 kidney specimens. Pancreas of 13/14 patients showed interstitial fibrosis and exocrine atrophy. Various pathologic findings such as renal tubular dysgenesis, paucity of hepatic bile ducts and iron storage in the macrophages of spleen and pulmonary alveoli were observed in some cases. Previous extensive clinical genetic and laboratory investigations have revealed that the patients had a previously unrecognized genetic disease. It is inherited as an autosomal recessive trait. The gene locus is 2q33-37. The basic defect of the disease remains unknown.
Subject(s)
Acidosis, Lactic/metabolism , Fetal Growth Retardation/mortality , Fetal Growth Retardation/pathology , Iron/metabolism , Iron/pharmacology , Renal Aminoacidurias/pathology , Age Factors , Autopsy , Birth Weight , Female , Fetal Growth Retardation/complications , Gestational Age , Hepatocytes/metabolism , Humans , Infant , Infant, Newborn , Liver/pathology , Male , Renal Aminoacidurias/complications , Syndrome , Time FactorsABSTRACT
We present clinical, biochemical and cranial magnetic resonance imaging data of six pediatric patients with L-2-hydroxyglutaric aciduria. All the children have the same ethic origin and lived in the northern area of Portugal. Our findings reinforce the described phenotype of this rare metabolic disease with mental deficiency, severe cerebellar dysfunction, mild extrapyramidal and pyramidal symptoms, progressive macrocephaly and seizures. Magnetic resonance imaging revealed subcortical leukoencephalopathy, cerebellar atrophy and signal changes in the putamina and dentate nuclei. These were similar to those of the previous reports in all patients. The urinary excretion of L-2-hydroxyglutaric acid was variably increased in all patients. The other persistent biochemical abnormality was hyperlysinemia. We have found a strong correlation between the severity of the clinical manifestations and the extension of the lesions in the neuroimaging studies. There was no correlation between the clinical findings and the amount of urinary excretion of L-2-hydroxyglutaric acid. We report the second case in the literature of a cerebral thalamic tumor in L-2-hydroxyglutaric aciduria; neuropathological examination of the surgical biopsy demonstrated a diffuse fibrillary astrocytoma.
Subject(s)
Glutarates/urine , Intellectual Disability/complications , Metabolism, Inborn Errors/complications , Renal Aminoacidurias/complications , Adolescent , Ataxia/complications , Ataxia/diagnostic imaging , Ataxia/pathology , Biopsy , Brain/diagnostic imaging , Brain/pathology , Child , Child, Preschool , Female , Humans , Intellectual Disability/diagnostic imaging , Intellectual Disability/pathology , Magnetic Resonance Imaging , Male , Metabolism, Inborn Errors/pathology , Metabolism, Inborn Errors/urine , Portugal , Renal Aminoacidurias/pathology , Renal Aminoacidurias/urine , Tomography, X-Ray ComputedABSTRACT
We report on an infant with D-2-hydroxyglutaric aciduria, who presented with severe seizures and developmental delay. We reviewed the literature for 2-hydroxyglutaric aciduria and found six other patients with the D-isomer and 24 patients with the L-isomer. Although the clinical spectrum of this inborn error of metabolism is variable, the clinical course of the D-form seems to be more severe than this of the L-form.
Subject(s)
Glutarates/urine , Renal Aminoacidurias/diagnosis , Epilepsy/diagnosis , Epilepsy/etiology , Glutarates/chemistry , Humans , Infant , Isomerism , Male , Psychomotor Disorders/diagnosis , Psychomotor Disorders/etiology , Renal Aminoacidurias/complications , Renal Aminoacidurias/urineABSTRACT
315 mentally retarded children from the coastal districts of Andhra Pradesh, south India, were screened to detect metabolic defects. Results with 2 cases of Hunter's syndrome, 1 case of Sanfilippo's syndrome and an unusual case of hyperamino aciduria are presented.
Subject(s)
Intellectual Disability/complications , Mucopolysaccharidoses/complications , Renal Aminoacidurias/complications , Adolescent , Child , Child, Preschool , Consanguinity , Female , Humans , Male , Mass Screening , Pedigree , Pilot ProjectsABSTRACT
An 18-year-old male, originally diagnosed as suffering from infantile autism but with a developmental history and clinical picture in keeping with Asperger's syndrome, and showing current signs of impairment of higher cerebral functioning, is presented. The subject and several males of his family present behavioural disturbances of an enduring type. An aminoaciduria was discovered in the subject and his father. A possible relationship between the metabolic disturbance and the neurological and behavioural disturbance is raised. Mechanisms for this relationship are discussed, including sporadic hyperlysinaemia.
Subject(s)
Autistic Disorder/complications , Renal Aminoacidurias/complications , Adolescent , Autistic Disorder/genetics , Humans , Male , Renal Aminoacidurias/geneticsABSTRACT
A patient with Netherton's syndrome who was followed since birth had previously been diagnosed as having Leiner's disease and acrodermatitis enteropathica; the disorder was recognized clinically when the patient was 20 years of age. Therapy with 13-cis-retinoic acid significantly aggravated the ichthyosis and induced increased fragility of the skin. This patient also had an intermittent aminoaciduria with clinical investigations that showed normal renal function. Furthermore, the aminoaciduria resolved spontaneously after the discontinuance of topically applied corticosteroids. The normal results of clinical studies and a review of the literature suggest that the aminoaciduria may have been artifactual because excess absorption of topically applied corticosteroids directly affects the renal tubules and impairs renal reabsorption or enhances the free excretion of amino acids. We review forty-two other cases of Netherton's syndrome in the literature and reaffirm the significance of associated ichthyosis, atopy, trichorrhexis invaginata, and other findings in this unique syndrome.
Subject(s)
Dermatitis, Atopic/genetics , Hair Diseases/genetics , Ichthyosis/genetics , Adult , Dermatitis, Atopic/pathology , Dermatitis, Atopic/therapy , Diagnosis, Differential , Follow-Up Studies , Hair/pathology , Hair Diseases/pathology , Hair Diseases/therapy , Humans , Ichthyosis/pathology , Ichthyosis/therapy , Male , Renal Aminoacidurias/complications , Skin/pathology , Syndrome , Time FactorsSubject(s)
Dermatitis, Atopic/genetics , Child , Child, Preschool , Dermatitis, Atopic/complications , Female , Hair/abnormalities , Hair/growth & development , Hair Diseases/complications , Hair Diseases/physiopathology , Humans , Intellectual Disability/complications , Male , Renal Aminoacidurias/complications , SyndromeSubject(s)
Amino Acid Metabolism, Inborn Errors/genetics , Brain Diseases/etiology , Malabsorption Syndromes/genetics , Renal Aminoacidurias/complications , Adolescent , Adult , Amino Acid Metabolism, Inborn Errors/complications , Child , Child, Preschool , Cystinuria/complications , Female , Humans , Infant , Intellectual Disability/etiology , Kidney Calculi/complications , Leucine/urine , Malabsorption Syndromes/complications , Male , Marfan Syndrome/complications , Nephrotic Syndrome/complications , Phenylalanine/urine , Phenylketonurias/complications , Valine/urineSubject(s)
Amino Acids/blood , Cystinuria/metabolism , Renal Aminoacidurias/diagnosis , Adolescent , Adult , Aged , Amino Acids/urine , Child , Cystinuria/complications , Female , Humans , Infant , Male , Middle Aged , Renal Aminoacidurias/complicationsSubject(s)
Amino Acid Metabolism, Inborn Errors/complications , Eye Manifestations , Renal Aminoacidurias/complications , Renal Tubular Transport, Inborn Errors/complications , Cystinosis/complications , Hartnup Disease/complications , Homocystinuria/complications , Humans , Leucine/metabolism , Oculocerebrorenal Syndrome/complicationsABSTRACT
Quantitative urinary amino acid excretion has been studied in 23 adult patients with mild phosphate diabetes (MPD), in 22 adult control patients with various renal disorders and in 15 children, 7--19 years old, with atopic disorders (normal controls). Statistically significant increases in urinary excretion of glutamine (p < 0.01), glycine (p < 0.01) and cystine (p < 0.05) were found in the MPD patients compared to the normal controls. The urinary excretion of glutamine was significantly increased while the increases in cystine and glycine excretions were non-significant when MPD patients were compared to the control patients. In addition to clinical signs and analyses of plasma and urinary phosphate, a quantitative evaluation of urinary amino acids might be a tool in the diagnosis of MPD. The significance of the increased urinary amino acid excretion in MPD is discussed.
Subject(s)
Hypophosphatemia, Familial/metabolism , Phosphates/urine , Renal Aminoacidurias/complications , Adult , Cystine , Cystinuria , Female , Glutamine/urine , Glycine/urine , Humans , Hypophosphatemia, Familial/complications , Male , Middle AgedABSTRACT
In distal (type 1) RTA, renal acid excretion is impaired by the inability to establish adequate pH gradients between plasma and distal tubular fluid at any level of acidosis. Main clinical signs in infancy are anorexia, vomiting and failure to thrive. Despite low serum bicarbonate levels the renal threshold of bicarbonate is normal, while urinary pH levels are high even with values below the threshold. Under conditions of bicarbonate-induced systemic alkalosis urinary the pCO2 exceeds blood pCO2 in normal subjects. by contrast, the urinary pCO2 tension is not significantly greater in distal RTA, indicating a failure of the cells of the distal nephron to secrete hydrogen ions even without a gradient. Red cell carbonic anhydrase is within the normal range, whilst the inhibition of carbonic anhydrase activity has no effect on distal tubular function. Until now no histological or enzymatic defect could be detected to explain the ineffective acidification. Bicarbonate loading is followed by a lowering of calcium excretion to within the normal range and a decrease in the uncharacteristic renal hyperaminoaciduria.