Alexander disease with serial MRS and a new mutation in the glial fibrillary acidic protein gene.
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Acidosis, Respiratory↗
Biomedical subjects
B K Burton
Publications and source records attributed to B K Burton.
Urea cycle disorders.
Deficiency of any of the five enzymes in the urea cycle results in the accumulation of ammonia and leads to encephalopathy. Episodes of encephalopathy and associated symptoms are unpredictable and, if untreated, are lethal or produce devastating neurologic sequelae in long-term survivors. Although these disorders do not produce liver disease, the consequences of hyperammonemia resemble those seen in patients with hepatic failure or in a transient interference with the urea cycle, as seen in some forms of organic acidemias. Therefore, investigation for hyperammonemia in any infant or child with altered mental status (in the absence of obvious causes, such as trauma, infection, or poisoning) is essential for prompt diagnosis of urea cycle disorders and institution of treatment to avoid brain damage and death. This article addresses the function of the urea cycle and the diagnosis and management of urea cycle disorders.
Amino Acid Metabolism, Inborn Errors↗
Mosaic trisomy 7 in a patient with pigmentary abnormalities.
Somatic chromosomal mosaicism may present as isolated pigmentary abnormalities or multiple congenital anomalies with mental retardation. Pigmentary lesions are visually dramatic and are differentiated based on appearance when the underlying pathogenesis is not known. It is now clear that mosaicism is responsible for the pigmentary findings in hypomelanosis of Ito (HI) and linear and whorled nevoid hypermelanosis (LWH). Both hypopigmentation and hyperpigmentation have been noted in the same individual, and both LWH and HI can be caused by similar chromosomal abnormalities. Both of these conditions exhibit similar systemic involvement. We present a case of LWH associated with mosaic trisomy 7 and review the relevant literature.
Child, Preschool↗
Effect of long-term beta-blockade on aortic root compliance in patients with Marfan syndrome.
BACKGROUND: This study was undertaken to assess the effect of long-term beta-blockade on the aortic root stiffness index and distensibility in patients with Marfan syndrome. METHODS: Aortic root stiffness index and distensibility were calculated according to the formulas of Stefanadis and Hirai, respectively, with 2-dimensional guided M-mode echocardiogram before and after an average of 26 months of atenolol administration. RESULTS: Twenty-three asymptomatic patients were studied (11 men and 12 women, aged 31 +/- 14.2 years). The follow-up was 4 +/- 2.2 years. The dose of atenolol was individualized (mean 43.5 +/- 21.6 mg/d). Heart rate decreased from 79 +/- 9 beats/min to 64 +/- 9 beats/min (P =. 01), and systolic blood pressure decreased from 124 +/- 13 mm Hg to 114 +/- 2 mm Hg (P =.01). Distensibility increased from 1.85 +/- 0. 70 x 10(-6) cm2/dynes-1 to 2.21 +/- 0.76 x 10-6 cm2/dynes-1 (P =.02), and the stiffness index decreased from 9.68 +/- 3.78 to 8.85 +/- 3. 15 ( P =.2). Two groups of responses to treatment were identified. Compared with baseline values 15 (65%) patients who responded to treatment had increased distensibility and decreased stiffness index of the aortic root (P =.05). Eight patients (35%) who did not respond to treatment had no significant change. Body weight >91 kg and baseline end-diastolic aortic root diameter >40 mm were significantly associated with no response (P =.05). Two patients in the nonresponding group had echocardiographic progression of aortic insufficiency. CONCLUSIONS: There was a heterogeneous response in the aortic root elastic properties after long-term treatment with atenolol in asymptomatic patients with Marfan syndrome. Stiffness index and distensibility are more likely to respond when the baseline end-diastolic aortic root diameter is <40 mm.
Adrenergic beta-Antagonists↗
Correction of ureagenesis after gene transfer in an animal model and after liver transplantation in humans with ornithine transcarbamylase deficiency.
We report effects of gene transfer and liver transplantation on urea synthesis in ornithine transcarbamylase deficiency (OTCD). We measured the formation of [15N] urea after oral administration of 15NH4Cl in two girls with partial OTCD before and after liver transplantation. Ureagenesis was less than 20% of that observed in controls before transplantation, and was normalized afterward. Studies performed on the OTCD sparse fur (spf/Y) mouse showed discordance between OTC enzyme activity and ureagenesis with modest increases in OTC enzyme activity after gene transfer resulting in significant improvement in ureagenesis. This study suggests that both liver transplantation and gene therapy may be effective in improving ureagenesis in OTCD.
Animals↗
Inborn errors of metabolism in infancy: a guide to diagnosis.
Recent advances in the diagnosis and treatment of inborn errors of metabolism have improved substantially the prognosis for many of these conditions. This makes it essential that the practicing pediatrician be familiar with the clinical presentation of these disorders. A practical clinical approach to the recognition of inborn errors of metabolism in the young infant is presented in this review. Indications for specific laboratory studies are discussed. Guidelines are provided for the stabilization and emergency treatment of critically ill infants. This approach will identify those infants who will benefit from additional evaluation and specific treatment. Many of the inborn errors of metabolism, including urea cycle defects, organic acidemias, and certain disorders of amino acid metabolism, present in the young infant with symptoms of an acute or chronic metabolic encephalopathy. Typical symptoms include lethargy, poor feeding, apnea or tachypnea, and recurrent vomiting. Metabolic acidosis and/or hyperammonemia are observed in many of these conditions, but there are notable exceptions, including nonketotic hyperglycinemia and molybdenum co-factor deficiency. Therefore, appropriate laboratory testing for metabolic disorders should be performed in any infant who exhibits these findings. Although sepsis may be the initial consideration in a neonate with these symptoms, inborn errors of metabolism should always be in the differential diagnosis, particularly in a full-term infant with no specific risk factors. Hypoglycemia may be the predominant finding in a number of inborn errors of metabolism, including glycogen storage disorders, defects in gluconeogenesis, and fatty acid oxidation defects. The latter disorders, among the most common encountered, exhibit marked clinical variability and also may present as a sudden death, a Reye's-like episode, or a cardiomyopathy. Jaundice or other evidence of hepatic dysfunction is the mode of presentation of another important group of inborn errors of metabolism including galactosemia, hereditary tyrosinemia, neonatal hemochromatosis, and a number of other conditions. A subset of lysosomal storage disorders may present very early with coarse facial features, organomegaly, or even hydrops fetalis. Specific patterns of dysmorphic features and congenital anomalies characterize yet another group of inherited metabolic disorders, such as Zellweger syndrome and the Smith-Lemli-Opitz syndrome. Each of these symptom complexes, and the appropriate evaluation of the affected infants, is discussed in more detail in this review.
Acidosis↗
Three novel fibrillin mutations in exons 25 and 27: classic versus neonatal Marfan syndrome.
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DNA Mutational Analysis↗
Malignant ventricular dysrhythmias in a patient with isovaleric acidemia receiving general and local anesthesia for suction lipectomy.
We report the occurrence of severe ventricular arrhythmias in a patient with isovaleric acidemia during general anesthesia for suction lipectomy. The timing of events and character of the ECG changes are most consistent with bupivacaine toxicity after subcutaneous injection of tumescence solution containing this local anesthetic. The patient had previously documented carnitine deficiency, a condition which, we speculate, may lower the threshold for bupivacaine induced cardiotoxicity. We review clinical considerations in isovaleric acidemia and conclude that the use of bupivacaine in these patients probably should be avoided.
Acidosis↗
Pregnancy outcome in women with low midtrimester maternal serum unconjugated estriol.
OBJECTIVE: To determine if unexplained low second-trimester maternal serum unconjugated estriol (MSuE3) is a useful predictor of complications of pregnancy. STUDY DESIGN: Between February 1, 1990, and January 3, 1993, 10,492 patients underwent prenatal screening using second-trimester maternal serum alpha-fetoprotein (MSAFP), maternal serum human chorionic gonadotropin (MShCG) and MSuE3. One hundred ninety-five patients with complete obstetric history/delivery records and with < 0.4 multiples of the median (MoM) second-trimester MSuE3 values were matched with 261 controls with complete obstetric history/delivery records and normal second-trimester MSAFP, MSuE3 and MShCG. RESULTS: The relative risk of pregnancy loss, as compared to that in controls, was 3.7 (1.4-9.1 confidence interval [CI], P < .0001) in patients with 0.2-0.4 MoM MSuE3 and 19.3 (6.1-60.5 CI, P < .0001) in patients with < 0.2 MoM MSuE3. After exclusion of patients with low and high MSAFP and MShCG, the relative risk of pregnancy loss for the remaining patients with low MSuE3 was 3.3 (1.3-8.5 CI, P < .008). CONCLUSION: The data suggest that patients with unexplained low second-trimester MSuE3 have an increased risk of pregnancy loss that may not be associated with a high or low MSAFP, MShCG or higher incidence of pregnancy-induced hypertension, gestational diabetes, premature rupture of membranes or premature onset of labor.
Adult↗
An increased incidence of haemangiomas in infants born following chorionic villus sampling (CVS).
The incidence of haemangiomas was ascertained by questionnaire in infants born to 578 consecutive CVS patients and 445 consecutive mid-trimester amniocentesis patients seen at a single institution between 1 January 1989 and 31 May 1991. The incidence of 7.4 per cent reported in the amniocentesis group was comparable to previous estimates of the incidence of haemangiomas in the general population. In contrast, a 21.1 per cent incidence, three-fold higher than that observed in the amniocentesis group, was observed among CVS-exposed infants (P < 0.001). This increased incidence was largely confined to patients undergoing a transcervical procedure. No correlation was observed between the incidence of haemangiomas and gestational age at sampling, sample size, number of sampling attempts, or a history of bleeding following the procedure.
Abdomen↗
Opitz syndrome is genetically heterogeneous, with one locus on Xp22, and a second locus on 22q11.2.
Opitz syndrome (OS, McKusick 145410) is a well described genetic syndrome affecting multiple organ systems whose cardinal manifestations include widely spaced eyes and hypospadias (Fig. 1). It was first reported as two separate entities, BBB syndrome, and G syndrome. However, subsequent reports of families in which the BBB and G syndrome segregated within a single kindred suggested that they were a single clinical entity. Although the original pedigrees were consistent with X-linked and autosomal dominant inheritance, male-to-male transmission in subsequent reports suggested that OS was inherited as an autosomal dominant trait. Here we report that OS is a heterogeneous disorder, with an X-linked and an autosomal locus. Three families were linked to DXS987 in Xp22, with a lod score of 3.53 at zero recombination. Five families were linked to D22S345 from chromosome 22q11.2, with a lod score of 3.53 at zero recombination. This represents the first classic multiple congenital anomaly syndrome with an X-linked and an autosomal form.
Abnormalities, Multiple↗
Microcephaly, lymphedema, and chorioretinal dysplasia: report of two additional cases.
In recent years, several patients with microcephaly, lymphedema and chorioretinal dysplasia have been described. We have studied two additional patients with similar findings. The question of whether microcephaly with lymphedema and microcephaly with chorioretinal dysplasia and lymphedema are distinct entities remains unanswered. Identification of other patients in the future may provide additional information.
Abnormalities, Multiple↗
Oromandibular-limb hypogenesis syndrome following chorionic villus sampling.
A female infant with hypoglossia-hypodactyly syndrome is presented. Her mother underwent chorionic villus sampling (CVS) at 9 weeks gestation. This is the seventh reported case of oromandibular-limb hypogenesis syndrome associated with maternal CVS, the first from the United States. These seven CVS-related cases represent a significant increase over this syndrome's 'natural' incidence of 1 per 175,000 live births. An excess of limb reduction deformities has also been seen following CVS. These seven cases are reviewed, and the possible etiology of this rare condition is discussed.
Chorionic Villi Sampling↗
A prospective trial of prenatal screening for Down syndrome by means of maternal serum alpha-fetoprotein, human chorionic gonadotropin, and unconjugated estriol.
OBJECTIVE: Our purpose was to prospectively evaluate the effectiveness of prenatal screening for Down syndrome by means of multiple serum markers. STUDY DESIGN: alpha-Fetoprotein, human chorionic gonadotropin, and unconjugated estriol were measured in 8233 midtrimester serum samples, including 7492 from women < 35 years old and 741 from women > or = 35 years old. Down syndrome risks were computed by means of age and all three markers. Further testing was recommended for patients with a risk > or = 1:270. Testing for trisomy 18 was recommended for patients with an alpha-fetoprotein < or = 0.70 multiples of the median, human chorionic gonadotropin < or = 0.50 multiples of the median, and unconjugated estriol < or = 0.55 multiples of the median. RESULTS: Of women screened initially 10.4% had a Down syndrome risk > or = 1:270; 10 of 12 known cases of Down syndrome were identified. One abnormality was detected for every 33 amniocenteses performed in this group. Of 0.4% of patients at increased risk for trisomy 18, two cases of trisomy 18 and one of triploidy were found. CONCLUSION: Multiple marker screening is effective in identifying the majority of fetal chromosome anomalies.
Adolescent↗
Spectrum of limb disruption defects associated with chorionic villus sampling.
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Abnormalities, Multiple↗
Limb anomalies associated with chorionic villus sampling.
Data on outcome of pregnancy were obtained in 436 (94%) of 463 patients undergoing chorionic villus sampling (CVS) at Humana Hospital-Michael Reese between January 1, 1989 and November 30, 1990. There were 18 elective abortions, 27 fetal and neonatal losses, and 391 surviving infants. Of the 394 fetuses and infants who were adequately evaluated, a total of 13 (3.3%) had major congenital anomalies, including four with transverse limb reduction deformities, three with cleft lip with or without cleft palate, and one each with a nasal encephalocele, large port-wine stain, craniosynostosis, omphalocele with associated defects, ambiguous genitalia, and undescended testes. The limb malformations in the four affected infants were all very similar and were comparable to those described by others in association with CVS. Three of the cases of limb malformations followed transcervical CVS; one followed a transabdominal procedure. The procedures were performed at 9.5, 9.5, 10.5, and 11 weeks' gestation. An adequate sample was obtained with a single attempt in each case. These observations, in conjunction with others in the literature, suggest that there is an increased risk of limb anomalies associated with CVS. A vascular etiology, related to either decreased fetal perfusion or thrombosis of the sampling site with subsequent embolization, is suggested.
Chorionic Villi Sampling↗
First report of management and outcome of pregnancies associated with hereditary orotic aciduria.
Two pregnancies in a 25-year-old woman with hereditary orotic aciduria who was managed prenatally on uridine therapy are described. The first pregnancy resulted in an infant with multiple congenital anomalies and a 47,xx,inv(4)(p12q25), +der(22)t(11;22)(p23;q11) karyotype. The proposita was found to be a carrier of a de novo 11;22 translocation and a pericentric inversion of chromosome 4. Subsequently, several carriers of orotic aciduria in this family were identified with the inverted chromosome 4. The second pregnancy resulted in a normal male with an inverted chromosome 4.
Abnormalities, Multiple↗