1/43. Therapeutic plasma exchange in patients with chylomicronemia syndrome complicated by acute pancreatitis.Chylomicronemia syndrome (CMS) is a rare disorder characterized by the presence of chylomicrons in the fasting state causing a milky appearance of plasma, eruptive xanthomas, and hepatosplenomegaly; an acute and potentially life threatening complication is severe acute pancreatitis. The underlying defects are inborn errors of metabolism such as deficiencies of lipoprotein lipase (LPL) or apoprotein C-II (apo C-II) as well as familial hypertriglyceridemia. Moreover, CMS can be precipitated when mild hypertriglyceridemia is exacerbated by additional factors such diabetes mellitus, ethanol abuse, or pregnancy. The purpose of the present study was to retrospectively analyze the results of therapeutic plasma exchange (TPE) in 5 patients transferred to our hospital for severe acute pancreatitis due to chylomicronemia syndrome. In a total of 7 TPE sessions, on average 3,286 /- 247 ml of plasma (i.e., about 1 patient plasma volume) were treated per session. Triglyceride (TG) levels were decreased from 4,972 /- 2,469 mg/dl on admission to 1,614 /- 1,276 mg/dl (-70%) after the TPE sessions, and a further decrease was achieved by conservative treatment. Part of the TG reducing effect of the treatment was probably due to heparin induced lipolysis. Acute pancreatitis was resolved in all cases, and 1 pregnant patient delivered without problems at term. In summary, 1 or 2 TPE sessions sufficed to substantially decrease the bulk of triglycerides in acutely exacerbated chylomicronemia syndrome causing a rapid resolution of acute severe pancreatitis.- - - - - - - - - - ranking = 1keywords = inborn error, metabolism, error (Clic here for more details about this article) |
2/43. Hypoketotic hypoglycemic coma in a 21-month-old child.We present the case of a 21-month-old child with hypoketotic hypoglycemic coma. The differential diagnosis initially included metabolic causes versus a toxicologic emergency (unripe ackee fruit poisoning). Using information obtained from the emergency department, the diagnosis was confirmed as the late-onset form of glutaric acidemia type II. This case illustrates the importance of emergency physicians in the diagnosis and management of children with inborn errors of metabolism.- - - - - - - - - - ranking = 1keywords = inborn error, metabolism, error (Clic here for more details about this article) |
3/43. delayed diagnosis of fatal medium-chain acyl-CoA dehydrogenase deficiency in a child.A 5-year-old white female presented with coma and died unexpectedly. She had a history of recurrent episodes of febrile illnesses associated with lethargy and coma. Postmortem investigation revealed a fatty liver, leading to a suspicion of inborn error of fatty acid oxidation. The diagnosis of medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was suggested by abnormal acylcarnitine profile with increased octanoylcarnitine in the blood, and confirmed by fatty acid oxidation studies and mutation analysis in skin fibroblast cultures. This case emphasizes the need to consider fatty acid oxidation disorders in all children who present with hypoglycemia with absent or mild ketones in the urine and high anion gap metabolic acidosis.- - - - - - - - - - ranking = 0.96669950593014keywords = inborn error, error (Clic here for more details about this article) |
4/43. Long-chain 3-hydroxyacyl-coa dehydrogenase deficiency: a case example in developmental disabilities.Long-chain 3-hydroxyacyl-coa dehydrogenase (LCHAD) deficiency is a rare autosomal recessive disorder with varied expression, from severe hypoglycemia and possible sudden infant death to neurosensory deficits secondary to the acute onset. The neurosensory deficits can include clinical features such as seizure disorders, mental retardation, neuropathy, and retinopathy. The basic defect is the lack of the LCHAD enzyme in the liver, which is necessary for fatty acid metabolism. The condition is usually precipitated by infection and dehydration. A case example of a preschooler with LCHAD deficiency is presented to show the complexity of this disorder and resultant developmental disabilities. Implications for nursing practice, education, and research are discussed in relation to the needs of families with complex, developmental disabilities.- - - - - - - - - - ranking = 0.033300494069864keywords = metabolism (Clic here for more details about this article) |
5/43. High cognitive outcome in an adolescent with mut- methylmalonic acidemia.Methylmalonic acidemia is an inborn error of metabolism known to be a cause of ketoacidosis and mental retardation. The less severe mut(-) form of the disorder, however, has been described with only mild to moderate cognitive deficits or, rarely, with normal neurodevelopment in asymptomatic cases. Nevertheless, there has been no detailed documentation of long-term neuropsychological function in the mut(-) form and relatively few IQ scores. We performed longitudinal developmental and neuropsychological assessments on a girl with symptomatic mut(-) methylmalonic acidemia whose biochemical abnormalities were in the moderately severe range and who had had recurrent episodes of ketoacidosis. At almost 12 years of age, her full scale IQ on the Wechsler intelligence Scale, third edition, was 129 with very superior and superior scores on nonverbal and verbal skills, respectively. On the National achievement Test she scored above the 99th percentile in the Basic Battery and is considered to be a gifted student. This outcome suggests that the spectrum of cognitive attainment in mut(-) methylmalonic acidemia is wide and that even a moderate degree of biochemical severity with ketoacidotic episodes may not result in cognitive deficit. Am. J. Med. Genet. (Neuropsychiatr. Genet.) 96:192-195, 2000.- - - - - - - - - - ranking = 1keywords = inborn error, metabolism, error (Clic here for more details about this article) |
6/43. Progressive infantile neurodegeneration caused by 2-methyl-3-hydroxybutyryl-CoA dehydrogenase deficiency: a novel inborn error of branched-chain fatty acid and isoleucine metabolism.We report a novel inborn error of metabolism identified in a child with an unusual neurodegenerative disease. The male patient was born at term and recovered well from a postnatal episode of metabolic decompensation and lactic acidosis. Psychomotor development in the first year of life was only moderately delayed. After 14 mo of age, there was progressive loss of mental and motor skills; at 2 years of age, he was severely retarded with marked restlessness, choreoathetoid movements, absence of directed hand movements, marked hypotonia and little reaction to external stimuli. Notable laboratory findings included marked elevations of urinary 2-methyl-3-hydroxybutyrate and tiglylglycine without elevation of 2-methylacetoacetate, mild elevations of lactate in CSF and blood, and a slightly abnormal acylcarnitine profile. These abnormalities became more apparent after isoleucine challenge. Enzyme studies showed absent activity of 2-methyl-3-hydroxybutyryl-CoA dehydrogenase (MHBD) in the mitochondrial oxidation of 2-methyl branched-chain fatty acids and isoleucine. Under dietary isoleucine restriction, neurologic symptoms stabilized over the next 7 months.- - - - - - - - - - ranking = 5keywords = inborn error, metabolism, error (Clic here for more details about this article) |
7/43. Identification of a fatty acid delta6-desaturase deficiency in human skin fibroblasts.Polyunsaturated fatty acid (PUFA) utilization was investigated in skin fibroblasts cultured from a female patient with an inherited abnormality in lipid metabolism. These deficient human skin fibroblasts (DF) converted 85;-95% less [1-14C]linoleic acid (18:2n-6) to arachidonic acid (20:4n-6), 95% less [3-14C]tetracosatetraenoic acid (24:4n-6) to docosapentaenoic acid (22:5n-6), and 95% less [1-14C]-linolenic acid (18:3n-3) and [3-14C]tetracosapentaenoic acid (24:5n-3) to docosahexaenoic acid (22:6n-3) than did normal human skin fibroblasts (NF). The only product formed by the DF cultures from [1-14C]tetradecadienoic acid (14:2n-6) was 18:2n-6. However, they produced 50;-90% as much 20:4n-6 as the NF cultures from [1-14C]hexadecatrienoic acid (16:3n-6), [1-14C]gamma-linolenic acid (18:3n-6), and [1-14C]dihomo-gamma-linolenic acid (20:3n-6), PUFA substrates that contain Delta6 double bonds. DF also contained 80% more 18:2n-6 and 25% less 20:4n-6. These results suggested that DF are deficient in Delta6 desaturation. This was confirmed by Northern blots demonstrating an 81;-94% decrease in Delta6-desaturase mRNA content in the DF cultures, whereas the Delta5-desaturase mRNA content was reduced by only 14%. This is the first inherited abnormality in human PUFA metabolism shown to be associated with a Delta6-desaturase deficiency. Furthermore, the finding that the 18- and 24-carbon substrates are equally affected suggests that a single enzyme carries out both Delta6 desaturation reactions in human PUFA metabolism.- - - - - - - - - - ranking = 0.099901482209593keywords = metabolism (Clic here for more details about this article) |
8/43. Anesthetic considerations for a patient with compound heterozygous medium-chain Acyl-CoA dehydrogenase deficiency.IMPLICATIONS: We describe the anesthetic management of a parturient with compound heterozygous medium chain acyl-CoA dehydrogenase deficiency, the most common disorder of fatty acid metabolism.- - - - - - - - - - ranking = 0.033300494069864keywords = metabolism (Clic here for more details about this article) |
9/43. Desmosterolosis presenting with multiple congenital anomalies and profound developmental delay.desmosterol (cholesta-5,24-dien-3beta-ol) is a minor sterol that forms as an intermediate in the cholesterol biosynthetic pathway when the 24-unsaturated sterol bond is reduced as the last step rather than earlier in the conversion of lanosterol to cholesterol. In 1998, FitzPatrick et al. reported a premature infant who died shortly after birth and had marked tissue elevations of desmosterol and a strikingly abnormal phenotype. We describe here the first living patient with desmosterolosis and show biochemical evidence in plasma and cultured lymphoblasts for an autosomal recessive deficiency of 24-dehydrocholesterol reductase (DHCR24). The infant has severe microcephaly, agenesis of the corpus callosum, downslanting palpebral fissures, micrognathia, submucous cleft palate, clubfoot, and a persistent patent ductus arteriosus. Plasma sterol quantification in the patient at age 2 years demonstrated a normal cholesterol level, but a 100-fold increased level of desmosterol (60 mcg/ml; nl 0.5 /- 0.3 mcg/ml (SD)) suggesting deficient activity of 24-dehydrocholesterol (desmosterol) reductase (DHCR24). Both parents had mildly increased levels of desmosterol in plasma (mother: 1.4 mcg/ml; father: 1.8 mcg/ml), consistent with heterozygosity for DHCR24 deficiency. Analysis of sterol metabolism in cultured transformed lymphoblasts showed a 100-fold increased level of desmosterol and a moderately decreased level of cholesterol in the patient's cells and a 10-fold elevation of desmosterol in the mother's cells. At the age of 3.5 years, the patient stands but does not walk, uses a 5-word vocabulary, and lacks any major medical problems. This unique patient broadens the spectrum of inborn errors of cholesterol biosynthesis and suggests additional candidate clinical phenotypes associated with abnormal cholesterol metabolism.- - - - - - - - - - ranking = 1.0333004940699keywords = inborn error, metabolism, error (Clic here for more details about this article) |
10/43. Lathosterolosis: an inborn error of human and murine cholesterol synthesis due to lathosterol 5-desaturase deficiency.Lathosterol 5-desaturase catalyzes the conversion of lathosterol to 7-dehydrocholesterol in the next to last step of cholesterol synthesis. Inborn errors of cholesterol synthesis underlie a group of human malformation syndromes including smith-lemli-opitz syndrome, desmosterolosis, child syndrome, CDPX2 and lathosterolosis. We disrupted the lathosterol 5-desaturase gene (Sc5d ) in order to further our understanding of the pathophysiological processes underlying these disorders and to gain insight into the corresponding human disorder. Sc5d (-/-) pups were stillborn, had elevated lathosterol and decreased cholesterol levels, had craniofacial defects including cleft palate and micrognathia, and limb patterning defects. Many of the malformations found in Sc5d (-/-) mice are consistent with impaired hedgehog signaling, and appear to be a result of decreased cholesterol rather than increased lathosterol. A patient initially described as atypical SLOS with mucolipidosis was shown to have lathosterolosis by biochemical and molecular analysis. We identified a homozygous mutation of SC5D (137A>C, Y46S) in this patient. An unique aspect of the lathosterolosis phenotype is the combination of a malformation syndrome with an intracellular storage defect.- - - - - - - - - - ranking = 3.8792601771248keywords = inborn error, error (Clic here for more details about this article) |
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