Lysosomal diseases diagnosis

The lysosomal disorder SASD is characterized by accumulation of the free acid monosaccharide sialic acid in the lysosomal compartment of the cell. Diagnosis is based on the demonstration of abnormal excretion of free, not OGS-bound sialic acid in urine, coupled with accumulation of free sialic acid in cultured fibroblasts, and on microscopic evidence of vacuoles (increased and swollen lysosomes filled with light electron-lucent material in skin biopsy and peripheral blood lymphocytes). The inheritance is autosomal recessive. There are different clinical forms of this disorder an adult form, called Salla disease (SD) or Finnish sialuria (OMIM 604369) infantile SASD (ISSD OMIM 269920) and an intermediate form, severe Salla disease [3,16]. 

Wenger DA, Coppola S, Liu SL (2003) Insight in the diagnosis and treatment of lysosomal storage diseases. Arch Neurol 60 322-328... 

Biochemically, I-cell disease is characterized by excessive secretion of newly synthesized lysosomal enzymes into body fluids and concomitant loss of respective intracellular activities in fibroblasts. Shown in Table 17-1 are representative lysosomal enzyme activity levels in serum from patients with I-cell disease and those with the closely related disorder pseudo-Hurler poly dystrophy, indicating significantly increased levels of lysosomal enzyme activity. Germane to the biochemical diagnosis is the characteristic pattern of lysosomal enzyme deficiency in cultured fibroblasts, that is, an increase in the ratio of extracellular to intracellular enzyme activity (Table 17-2). It is interesting to note that not all lysosomal (i.e. intracellular)... 

Prenatal diagnosis of I-cell disease has been based on greatly reduced phosphotransferase activity (cf. Biochemical Perspectives section) and abnormal intracellular-extracellular distribution of lysosomal enzymes in cultured amni-otic fluid cells (Table 17-3).As indicated in Table 17-3, amniotic fluid cells secrete large amounts of lysosomal enzymes into the extracellular medium. Decreased levels of lysosomal enzymes in chorionic villi obtained by biopsy have also been observed in I-cell disease however, the characteristic secondary effect (i.e.,increased levels of lysosomal enzymes in the extracellular compartment) is only partially expressed or not expressed at all in chorionic villi, suggesting an alternative mechanism for the transport of lysosomal proteins. Although... 

Alroy J, Ucci AA (2006) Skin biopsy a useful tool in the diagnosis of lysosomal storage diseases. 

Tay-Sachs disease is a fatal genetic disorder where harmful amounts of lipids called ganglioside accumulate in the nerve cells and brains of those affected. Infants with this disorder appear normal for the first several months of life, and then as the lipids distend the nerve cells and brain cells, progressive deterioration occurs the child becomes blind, deaf, and eventually unable to swallow. Tay-Sachs disease occurs mainly in Jewish children of Eastern European descent, and death from bronchopneumonia usually occurs by age 3 to 4 years. A reddish spot on the retina also develops, and symptoms first appear around 6 months of age. It is a lysosomal storage disorder with insufficient activity of the enzyme hexosaminidase A, which catalyzes the biodegradation of the gangliosides. The diagnosis is made by the clinical suspicion and serum hexosaminidase level. Currently there is no treatment available for this disease. 

Blom, W., Luteyn, J. C., Kelholt-Dijkman, H. H., Huijmans, J. G. M., and Loonen, M. C. B. (1983). Thin-layer chromatography of oligosaccharides in urine as a rapid indication for the diagnosis of lysosomal acid maltase deficiency (Pompe s disease). Clin. Chim. Acta 134 221-227. 

Fig. 19.3. Diagnostic flow-chart for patients with coarse Hurler-like face. Coffin-Lowry syndrome (MIM 303300) Coffin-Siris syndrome (MIM 135900) frontometaphyseal dysplasia (MIM 305620) Sotos syndrome (MIM 117550) Williams syndrome (MIM 194050) multiple neuroma syndrome (MIM 171400) pachydermoperiostosis (MIM 167100) acromegaloid facial appearance syndrome (MIM 102150) Costello syndrome (MIM 218040) Patterson David syndrome (MIM 169170) Schinzel-Giedeon syndrome (MIM 269150) Fountain syndrome (MIM 229120) Pallister-Killian syndrome (MIM 601803) Simpson-Golabi-Behmel syndrome (MIM 312870) congenital hypothyroidism. Sialic acid storage disease, a lysosomal transport defect (Chap. 20) should also be considered in the differential diagnosis...

---