1/10. Isolated sulfite oxidase deficiency: review of two cases in one family.OBJECTIVE: The authors describe two cases of isolated sulfite oxidase deficiency found in one family. This is a rare autosomal-recessive disorder presenting at birth with seizures, severe neurologic disease, and ectopia lentis. It can be easily missed with metabolic screening; however, the finding of lens subluxation stresses the importance of ophthalmic assessment in making the diagnosis. DESIGN: Two observational case reports. INTERVENTION/methods: Ophthalmic assessment, biochemical assay for specific urinary and plasma metabolites, magnetic resonance imaging, and gene sequencing were used to make the diagnosis of the disease in the proband. The diagnosis was subsequently recognized in a previously affected sibling after the postmortem neuropathology was reviewed. mutation analysis was performed on cultured fibroblasts from the proband to identify and categorize the specific mutation responsible for the disease in the family. From this, future prenatal detection of sulfite oxidase deficiency is possible. MAIN OUTCOME MEASURES: The diagnosis of sulfite oxidase deficiency was established in this family, enabling appropriate genetic counseling and recurrence risk estimation. RESULTS: Point mutations were found in both alleles of the sulfite oxidase gene in the proband. The first is a 623C-->A mutation, which predicts an A208D substitution, and the second is a 1109C-->A, which predicts an S370Y substitution. Both residues A208D and S370Y are critical for sulfite oxidase activity. CONCLUSIONS: Isolated sulfite oxidase deficiency is a rare heritable disease for which mutation analysis can allow accurate prenatal screening. It often is difficult to diagnose by clinical presentation alone, but the critical finding of lens subluxation accompanying seizures and diffuse neurologic disease in an infant should alert the physician to the diagnosis.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
2/10. Three cases of intravenous sodium benzoate and sodium phenylacetate toxicity occurring in the treatment of acute hyperammonaemia.Intravenous sodium benzoate and sodium phenylacetate have been used successfully in the treatment of acute hyperammonaemia in patients with urea cycle disorders. They provide alternative pathways for waste nitrogen disposal and help maintain nitrogen homeostasis. However, we report three patients with hyperammonaemia who received inappropriate doses of intravenous sodium benzoate and sodium phenylacetate that resulted in severe complications. Ambiguous medical prescriptions and inadequate cross-checking of drug dosage by physicians, nurses and pharmacists were the main causes of these incidents. All the patients presented with alteration in mental status, Kussmaul respiration and a partially compensated metabolic acidosis with an increased anion gap. Two patients developed cerebral oedema and hypotension and died. The third survived after haemodialysis. plasma levels of benzoate and phenylacetate were excessively high. The possible mechanisms of toxicity, management and safety measures are discussed.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
3/10. Lethal late onset cblB methylmalonic aciduria.OBJECTIVE: To alert the physicians to the possibility of a late-onset inborn error of metabolism in an apparently previously healthy patient with acute clinical presentation. DESIGN: Case report. SETTING: Pediatric unit and general intensive care unit. PATIENT: An apparently previously healthy 12-yr-old female presented acutely with vomiting, fever, bronchopneumonia, and progressive loss of consciousness associated with ketoacidosis, hyperglycemia, and hyperammonemia. She died 3 days later with a diagnosis of insulin-dependent diabetes mellitus. INTERVENTIONS: Intravenous hydration, glucose and insulin, mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Organic acid analysis on a postmortem sample of aqueous humor revealed high levels of methylmalonic acid. Enzymatic studies on cultured fibroblasts were consistent with the diagnosis of cblB methylmalonic aciduria. CONCLUSIONS: The diagnosis of cblB methylmalonic aciduria was made in a postmortem patient who died with a misdiagnosis of insulin-dependent diabetes mellitus. Unclear biochemical findings and positive family history should strongly lead to suspicion of an inborn error of metabolism in an apparently previously healthy critically ill patient.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
4/10. Establishing gas chromatography-mass spectrometry to diagnose organic acidemias in thailand.Disorders of organic acid metabolism are a group of disorders which has long been ignored by majority of Thai physicians. Part of this is due to lack of laboratories in thailand to verify the diagnosis of the disorders. We have recently developed a technique to qualitatively analyze organic acids utilizing gas chromatography-mass spectrometry (GC-MS). Eight patients in four families were successfully identified as having organic acidemias (OA) by this method. Two families had methylmalonic acidemia, one had propionic acidemia, and the other had 3-methylcrotonyl CoA carboxylase deficiency. To our knowledge, this is the first laboratory in thailand being able to use GC-MS to diagnose OA. Availability of a laboratory in thailand and affordability of the test are expected to result in earlier diagnosis and identification of more cases of OA in Southeast Asian countries. Consequently, prompt and proper treatment can be anticipated which should lead to better prognosis for patients with this group of disorder.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
5/10. adenine phosphoribosyltransferase deficiency and renal allograft dysfunction.adenine phosphoribosyltransferase (APRT) deficiency is a rarely diagnosed cause of renal allograft dysfunction. We report the case of a 42-year-old man who presented in 1996 with idiopathic renal failure. Native kidney biopsy showed extensive microcrystalline interstitial nephritis. The patient subsequently underwent a living-related kidney transplant with excellent early graft function. During the next year, however, he had worsening allograft function, and allograft biopsy showed recurrent interstitial nephritis. Further chemical and spectroscopic analysis showed this lesion to be an annular microcrystalline nephritis consistent with APRT deficiency. This diagnosis was confirmed on erythrocyte assay. Treatment with allopurinol and a low-purine diet led to improvement and stabilization of renal function. APRT is a rare cause of renal allograft dysfunction requiring a high index of suspicion for early diagnosis and treatment. Increased physician awareness in the united states may hasten diagnosis and limit the morbidity associated with this disease.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
6/10. L-2-Hydroxyglutaric aciduria presenting as status epilepticus.L-2-Hydroxyglutaric aciduria (L-2-HGA) is a rare organic aciduria with a slowly progressive course regarding CNS involvement. We present a 13.5-year-old female patient who presented at the Emergency Department with a generalized status epilepticus, which promptly responded to intravenous phenytoin. CT and MRI demonstrated subcortical white matter alterations. The neurological examination revealed mild mental retardation, macrocephaly and ataxic gait with cerebellar signs. Repeated urinary organic acid analysis demonstrated increased excretion of 2-hydroxyglutaric acid which was of the L-configuration. The constellation of macrocephaly in a patient with mental retardation, cerebellar tract involvement and subcortical white matter signal alterations on MRI should alert the physician to the possibility of L-2-HGA. Although rare, epileptic seizures or even status epilepticus can be among the presenting symptoms in organic acidurias with a slow course, such as L-2-HGA.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
7/10. urea cycle disorders in Thai infants: a report of 5 cases.urea Cycle Disorders (UCD) is an inborn error of urea synthesis in which ammonium and other nitrogenous precursors of urea accumulate leading to episodic coma and a high mortality rate. Therapy with peritoneal dialysis, essential amino acids or their nitrogen-free analogues has increased survival. The authors report 5 cases of urea cycle disorders, all of whom developed and were rescued from hyperammonemic coma. However, the eventual outcome was quite variable. argininosuccinate lyase deficiency (ALD) Case 1. A 2 month old male infant, a product of a consanguineous marriage (Suphanburi province); developed poor feeding on day 7, lethargy, convulsion, hepatomegaly and respiratory alkalosis leading to respiratory failure and coma. hyperammonemia, elevation of glutamic acid and argininosuccinic acid and its anhydrides confirmed the diagnosis of ALD. He is now 9 years old and severely retarded. Case 2. A male infant with history of lethargy, poor feeding on day 3, treated as sepsis and required respiratory support for 6 days; subsequently readmitted at age 2 weeks with vomitting, lethargy, seizure activity and hyperammonemia, and was treated by a local pediatrician in Songkhla province. There was a history of parental consanguinity and he was referred to Siriraj Hospital on day 64 with severe essential amino acid deficiency and acrodermatitis enteropathica with markedly elevated plasma citrulline level. In spite of aggressive treatment; the patient developed sepsis and he expired on day 78. ornithine transcarbamylase deficiency (OTC) Case 3. An eleven-month-old male infant, the product of a non-consanguineous marriage, developed neonatal onset of hyperammonemia on day 5 after poor feeding, lethargy, hypothermia, seizure, apnea and coma. He was rescued from neonatal hyperammonemic coma on day 9 after aggressive treatment, but expired at eleven months of age after overwhelming sepsis. Case 4. A male infant, sibling of case 3 was referred to Siriraj Hospital on day 8 with hyperammonemia and coma. In spite of intensive genetic counseling given after the birth of their first child with OTC, the couple chose to have another baby without informing any physician. The baby developed vomiting and lethargy on day 2; subsequently hyperammonemia was noted. In spite of aggressive treatment given; hepatic dysfunction, renal failure and disseminated intravascular coagulation defects occurred on day 15. He expired on day 18 after parental permission for discontinuation of all treatment. Argininosuccinate synthetase deficiency (ASS) or citrullinemia. Case 5. A seven week old female infant, the product of a consanguineous marriage and of Pakistani ethnic origin; developed intermittent vomiting from day 6. Initial diagnoses included ruminations, sepsis and pyloric stenosis for which she was operated on (day 30); however, vomiting continued; subsequently seizures, hyperammonemic coma developed and she was rescued from hyperammonemic coma within 30 hours. Significant elevations of citrulline and L-glutamine were demonstrated. She was discharged in excellent condition to her home in Dubai, the united arab emirates.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
8/10. retinitis pigmentosa in mevalonate kinase deficiency.retinitis pigmentosa can occur as a complication of mevalonate kinase deficiency. This may be due to the unique isoprenoid metabolism in the retina. Early detection requires awareness on the part of the treating physician.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
9/10. Fish-odor syndrome presenting as dysosmia.We describe a patient who had perceived an unpleasant odor or taste for at least 20 years. Several other physicians had unsuccessfully treated her for infections, mucus membrane dryness and inflammation, chronic tonsillitis, and psychiatric disorders. Her workup at the State University of new york health science Center at Syracuse Olfactory Referral Center included a thorough history, examinations (including endoscopic studies of her nose, pharynx, and lungs), roentgenograms, taste testing, olfactory testing, and selective anesthesia of her chemosensory areas. The perception occurred only during exhalation, and appeared to be binasal. These findings, together with her morning mucus sample having a strong fishlike odor, prompted us to suspect a metabolic problem. Further testing at the Monell-Jefferson Chemosensory Clinical research Center, philadelphia, Pa, confirmed that she had trimethylaminuria. It is important to consider this and other treatable conditions when evaluating individuals with olfactory complaints.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
10/10. Alpha-1-antitrypsin deficiency in childhood.alpha 1AT deficiency predisposes children to liver injury and adults to emphysema. Pi typing has clarified that the inherited deficiency is codominant. amniocentesis is unproved as a reliable technique in detecting the homozygous deficient patient (another controversial issue). Even if this procedure were to become diagnostic, present knowledge cannot predict the clinical course of each individual born with homozygous alpha 1AT deficiency, therefore confronting the physician and parents with a moral dilemma that neither of us feels comfortable with in regard to family counseling. Presently, we can only educate the family with the current state of the art summarized in this review. The fundamental steps in evaluating a child and the involved family are outlined in Table 2. Steps 1, 2 and 5 should be readily available. Pi typing can specifically identify susceptible individuals who can be counseled concerning work habits and known toxins such as smoking and alcohol. liver biopsy is not essential for diagnostic purposes but may prove to be prognostic concerning the child's ultimate outcome. More certain is the evidence that no infant should be explored for a bile duct lesion during the early cholestatic period because no surgical lesion will be found. Therefore, all children with infantile cholestasis should be evaluated for alpha 1AT deficiency prior to a laparotomy. Although medical therapy is only supportive at the present time, further research should eventually provide therapeutic approaches to the basic defect.- - - - - - - - - - ranking = 1keywords = physician (Clic here for more details about this article) |
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