Inborn errors of metabolism

Abstract

Inborn errors of metabolism often cause neurological dysfunction. These disorders are most common in childhood, but adult-onset forms with a different clinical presentation are encountered, examples being Pompe disease, Tay-Sachs disease, metachromatic leukodystrophy, Gaucher disease, and Maroteaux-Lamy disease. In the evaluation of a patient with a possible inborn error of metabolism, simple screening tests may aid in the diagnosis and provide direction for more comprehensive laboratory analysis. In most cases, diagnosis can be established without a brain biopsy through biochemical and ultrastructural analysis of peripheral tissues, blood, and urine. New clinical, genetic, and biochemical variants of inherited metabolic disorders are being recognized through wider application of screening tests, improved specificity of laboratory analysis, cell complementation experiments, and the identification of enzyme activator factors. Accurate diagnosis is important for medical management, determining prognosis, and genetic counseling.

Deficiency of aminopeptidase P1 causes behavioral hyperactivity, cognitive deficits, and hippocampal neurodegeneration

“…Individuals with IEM frequently exhibit intellectual disability (Kahler & Fahey ; Kolodny & Cable ; van Karnebeek & Stockler ), and Xpnpep1 −/− mice exhibit microcephaly (Yoon et al . ).…”

Eight-Year-Old Girl with Psychomotor Retardation and Seizures

“…The typical lysosomal inclusions are encountered in both neural and nonneural tissues including peripheral lymphocytes, fibroblasts, endothelial cells, Schwann cells, axons, macrophages, epithelial cells (especially ec crine sweat glands and ducts), skeletal muscle, smooth muscle, ganglionic plexus of the rectum and appendix and even urinary sediment [5,[8][9][10][11][12][13][14][15][16][17], This obviates the need for a brain biopsy and biopsies of skin, conjuncti va or skeletal muscle are more than adequate for diagno sis. In the bone marrow, a picture of sea-blue histiocytes is seen [5]; in the peripheral blood, vacuolated lympho cytes may be found [17].…”

Why screen newborns for profound and partial biotinidase deficiency?

“…However, these asymptomatic individuals are clearly the exceptions rather than the rule. In fact, there are multiple examples of adultonset, enzyme-deficient individuals with a variety of inherited metabolic diseases [24,25], including phenylketonuria [25,26]. We routinely admonish those individuals who are enzyme deficient and are not taking biotin that they may be at risk of developing symptoms, and it is probably most prudent for them to consider taking the vitamin, even as adults.…”