Metabolic disorders, congenital

Indications for the transplantation of hepatocytes predominantly involve those liver diseases in which functional failures occur in the liver cells (not in the bile ducts). Permanent transplantation would be indicated, for example, in order to eliminate congenital metabolic disorders of the liver cells. In this case, hepatocytes from the patient could be used, with subsequent elimination of the defect by gene technology, as well as hepatocytes from healthy donors. A few years ago, a therapeutic effect lasting for over one year was achieved for the first time in a girl suffering from the Crigler-Najjar syndrome (I. X Fox et af, 1998). Human hepatocytes are most definitely more suitable than animal liver cells. The latter may well meet the requirements for a provisional substitute, but not for permanent transplantation. 

Causes of fatty liver are manifold, and combinations of causes quite common. Acquired causes are by far the most frequent, but there are also rare causes, e.g. coeliac disease (9, 25), parenteral nutrition. (28, 29) Congenital metabolic disorders can also lead to the development of a fatty liver, as in the case of a rare thesaurismosis. It is of considerable therapeutic and prognostic importance to differentiate between an alcoholic fatty liver (AFL) and alcoholic steatohepatitis (ASH) (s. pp 529, 531) as well as between non-alcoholic fatty liver (NAFLD) and non-alcoholic steatohepatitis (NASH). (2, 20, 24, 36) (s. tabs. 31.5-31.7)... 

Hepatic disease hypersensitivity to valproate pregnancy (FDA category D) children < 2 years (especially those on multiple antiwnvulsant therapy, those with congenital metabolic disorders, those with severe seizure disorders, and those with organic brain disease) pancreatitis. 

Gross pathological lesions are almost invariably preceded by biochemical lesions, and hence derangement or overloading of biochemical processes may have important consequences w ith respect to food safety. This concept is discussed in relation to congenital metabolic disorders, enzyme inhibitors in food and drugs, and dose-response characteristics. 

Congenital, familial, and metabolic disorders (e.g., congenital obstructive uropathy, Fabry s disease, medullary cystic disease, and nephrolithiasis)... 

Diseases of muscle are usually classified as muscular dystrophies, inflammatory or congenital myopathies, metabolic disorders affecting the muscle, and neurological diseases affecting the innervation of the muscle (so-called motor neuron diseases). In the past, the energy metabolism of some muscular diseases... 

CFD is further associated with the following inherited metabolic disorders 5,10-methylen-tetrahydrofolate reductase (MTHFR) deficiency [7], 3-phos-phoglycerate dehydrogenase (PGDH) deficiency [8], dihydropteridine reductase (DHPR) deficiency [9], as well as with Rett syndrome [10], and Aicardi-Gou res Syndrome [11]. Furthermore, folate deficiency may be associated with congenital folate malabsorption, severe malnutrition, and formiminotransferase deficiency. 

A 5-day-old boy, weighing 2.3 kg, developed a metabolic acidosis after receiving topical dorzolamide for 1 week for bilateral Peter s anomaly (a congenital corneal disorder characterized by a central leukoma and adhesions at the periphery of the corneal opacity) (35). The maximum base deficit was 20.2 mmol/1. On withdrawal of topical dorzolamide his acidosis resolved within 1 day. 

Primary metabolic disorders and storage diseases are caused by endogenous factors, usually a gene mutation. Since the congenital defect is predominantly or exclusively located in the liver, the resulting diseases also become manifest in this organ. 

The most comprehensive and thorough analysis of the clinical outcomes of patients receiving home PN or EN comes from Medicare and the North American Home Parenteral and Enteral Patient Registry. It was estimated that 40,000 and 152,000 patients in the United States were receiving home PN and EN support, respectively. Patients with GI faUme, which included those with Crohn s disease, ischemic bowel disease, motility disorders, and congenital bowel defects had relatively good outcomes, especially when compared with the groups with cancer or AIDS. The patients with GI failme had an 87% annual survival rate and a 50% to 75% likelihood of complete rehabilitation. Sepsis, metabolic disorders, and mechanical problems with catheters resulted in one to two hospitalizations per year for aU patients. ... 

Infectious disorders Associated cardiac disorders Associated metabolic disorders Congenital disorders Unknown causes... 

Two of these incidents may have contributed to the death of a patient (a 10-fold morphine overdose in a premature, unstable patient and dysfunctional cerebral function monitoring that delayed treatment of seizures). Another five incidents were expected to result in permanent major harm 3-day delay in test results for congenital hypothyroid disorder, defective ventilator resulting in severe metabolic acidosis, arterial line occlusion resulting in foot necrosis, bums due to chlorhexidene, and skin necrosis after subcutaneous infusion of packed cell. 

Contents Causes of Diseases Abnormal Growths Aging and Degeneration of Tissues Allergies and Other Disorders of Immunity Congenital and Genetic Disorders Endocrine and Metabolic Disorders Injuries from Physical Agents Stresses... 

Several diseases are known that result in elevations in tissues and fluids of various esters of carnitine and reduce the availability of free carnitine, which is normally synthesized by humans and is necessary for the transport of long-chain fatty acids into mitochondria for oxidation. In several disorders arising from acyl-CoA dehydrogenase deficiencies, the accumulation of the acyl-CoA substrate frequently sequesters coenzyme A and reduces its availability for other unrelated but important and otherwise competent pathways. Carnitine administration can displace and make available much of the coenzyme A that had been isolated, and stimulate the excretion of the accumulating acidic metabolites now esterified to carnitine. Detection of reduced levels of serum or urinary free carnitine and elevations of esterified carnitine is therefore useful for diagnosis of a variety of metabolic disorders, among them congenital inability to synthesize carnitine. In this disorder, carnitine must be supplied by a carnitine-enriched diet as it is, in effect, a vitamin. 

Figure 2.1. Electrospray ionization mass spectrum of the glycoprotein transferrin from (a) a normal patient and (b) a patient with a metabolic disorder known as a CGD (congenital disorder of glycosylation). The mass spectrum of the patient with abnormal transferrin displays peaks (marked by stars) that are shifted in mass because the protein is missing an oligosaccharide chain. Mass spectrometric analysis of transferrin currently plays a central role in the clinical screening of patients for CGD. (Reprinted from Refs. 2 and 3, with permission.)...

To cover these various disorders in an orderly and comprehensive manner, the following sections are devoted, respectively, to the muscular dystrophies the congenital myopathies the metabolic myopathies the myotonias, periodic paralyses, and malignant hyperpyrexia the neurogenic disorders the inflammatory muscle disorders the endocrine myopathies and the drug-induced and toxic myopathies. 

OA is often divided into primary (idiopathic) and secondary disease (Table 55-1). Primary OA is the predominant form and occurs in the absence of a precipitating event. It may assume a localized, generalized, or erosive pattern. Localized OA is distinguished from generalized disease by the number of sites involved, whereas erosive disease is characterized by an erosive pattern of bone destruction and marked proliferation of interphalangeal joints of the hands. Secondary OA occurs when the disease is caused by congenital or developmental disorders or inflammatory, metabolic, or endocrine diseases. 

Secondary OA is associated with a known cause such as rheumatoid arthritis or another inflammatory arthritis, trauma, metabolic or endocrine disorders, and congenital factors. 

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