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- De Koning, Tom J., et al.
(författare)
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Amino Acid Synthesis Deficiencies
- 2022. - 2
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Ingår i: Physician's Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases, Second Edition. - Cham : Springer International Publishing. - 9783030721848 - 9783030721831 ; , s. 453-467
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Bokkapitel (refereegranskat)abstract
- In recent years the list of disorders affecting amino acid synthesis has grown rapidly. Not only the number of defects has increased, but also the associated clinical phenotypes have expanded spectacular, the latter mainly due to the advances of next-generation sequencing diagnostics. An important reason for the contribution of NGS in the diagnosis of amino acid synthesis disorders is the fact that the biochemical diagnosis of some of these synthesis disorders can be quite challenging, synthesis defects may present with low values of amino acids, or their concentrations can even be completely normal. Defects in the synthesis pathways of serine metabolism, glutamine, glutamate, proline, and asparagine have been reported, and all pose specific challenges to a biochemical diagnosis. An exception to this are the disorders of pyrroline-5-carboxylate (P5C) synthesis where ornithine or proline is strongly elevated and easily detected by plasma amino acid analysis. Finally, Snyder-Robinson, a defect in the synthesis of the polyamine spermine, is discussed here as well, and molecular testing is advised for this disorder as well. Although the amino acid synthesis defects in this chapter are not all in related metabolic pathways, they do share some clinical features. In children the central nervous system is primarily affected, giving rise to (congenital) microcephaly, early-onset seizures, and mental retardation to a variable degree. The brain abnormalities can be accompanied by skin disorders such as cutis laxa in proline defects, collodion-like skin and ichthyosis in serine deficiency, necrolytic erythema in glutamine deficiency, and difficult to classify skin abnormalities in glutaminase hyperactivity. In adults with serine or proline disorders, several forms of polyneuropathy with or without intellectual disability appear to be the major presenting symptom. An exception to this is ornithine aminotransferase deficiency which primarily affects the choroid and retina and Snyder-Robinson syndrome in which mental retardation is accompanied by seizures, dysmorphic features, and severe osteoporosis.
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| 3. |
- Nobili, Valerio, et al.
(författare)
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Tyrosinemia type 1: metastatic hepatoblastoma with a favorable outcome.
- 2010
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Ingår i: Pediatrics. - : American Academy of Pediatrics (AAP). - 1098-4275 .- 0031-4005. ; 126:1
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Tidskriftsartikel (refereegranskat)abstract
- The clinical course of tyrosinemia type 1 is characterized by acute liver failure in infancy or chronic liver dysfunction and renal Fanconi syndrome in late-presenting cases. Dietary treatment may improve liver function but does not prevent the development of hepatocellular carcinoma (HCC) in late childhood. A new treatment strategy that uses 2-(2-nitro-4-trifluoromethylbenzoyl)-1,3-cyclohexanedione (NTBC), which prevents the production of toxic/carcinogenic metabolites, has dramatically changed the outcome of the disease by reducing the occurrence of liver cancer, especially in patients who start this treatment before the age of 2 years. We report here the case of a patient with a diagnosis of tyrosinemia type 1 at 5 months of age who was treated with NTBC and dietary restriction and in whom a liver neoplasm with lung metastases, histologically determined to be HCC, was found at the age of 15 months. A conservative approach that consisted of chemotherapy and partial hepatectomy resulted in a 12-year disease-free period. The excellent postchemotherapy course, in sharp contrast to the expected course of HCC, led to histologic reevaluation with reclassification of the neoplasm as hepatoblastoma. A diagnosis of hepatoblastoma would no longer be a mandate for a liver transplant for patients with tyrosinemia type 1 undergoing NTBC treatment. We encourage clinicians to perform more accurate evaluation of liver histology, because a neoplastic mass in a child with tyrosinemia type 1 is not the same as HCC.
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