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A glycolipid is a fatty molecule which contains at least one sugar molecule as well; gangliosides are glycolipids which also contain a molecule called sialic acid. These molecules are important part of many cell membranes. In some genetic diseases, the enzymes needed to break down the gangliosides are deficient, and the gangliosides build up within cells. Such disorders are generally called gangliosidoses. They are genetically recessive, since just one normal enzyme gene inherited from just one parent is sufficient to prevent the metabolic disorder. One of the most common gangliosidoses is Tay-Sachs disease, in which a deficiency of an enzyme called hexosaminidase A results in the pathological accumulation of a specific ganglioside, GM2. Tay-Sachs disease is not the only disorder involving hexosaminidase A, however. While Tay-Sachs normally affects infants who then die early in life, there are more chronic forms of the enzyme deficiency. Seven cases from three different families illustrate the different manifestations of hexosaminidase A deficiency disorders. Two patients, a brother and sister, developed a ''juvenile'' type of the disorder, in which symptoms in early childhood progress, becoming fatal within a few years. The remaining patients developed the ''adult'' form of the disorder, which may be something of a misnomer; the ''adult'' form may also develop early in childhood, but it progresses more slowly and might therefore better be called the chronic form. Biochemical tests revealed that all patients had some measurable deficiency of hexosaminidase A. Two families had a peculiar deficiency in which the enzyme could digest an artificial compound used for the laboratory test but not the natural GM2 it is supposed to digest. Testing limited to the artificial compound would have missed the abnormality in these cases. The two patients from the remaining family had a measured enzymatic defect that was indistinguishable from that of Tay-Sachs disease. However, while Tay-Sachs patients die in infancy, these two brothers remain alive as teenagers, albeit with serious neurological deficits. Why the biochemical deficit should appear to be the same in these vastly different disorders is not understood, and illustrates the poorly understood relationship of disorders of hexosaminidase A and the clinical features of the disease which results. (Consumer Summary produced by Reliance Medical Information, Inc.)

Cerebrotendinous xanthomatosis (CTX) is an inherited lipid (fat) storage disorder. The condition, which is rare, results in the accumulation of cholesterol and cholestanol in all tissues, but most notably in the brain and the tendons. Symptoms of the disease include cataracts and xanthomas (slightly elevated fat-filled deposits, most common on the eyelids, but can affect many parts of the body). CTX also results in progressive neurological disease, which is eventually fatal. The authors report the case of an individual with symptomatic CTX. The patient, who had been retarded since infancy, was first seen in 1985 for dementia. Huge xanthomas were present on the Achilles tendon, as well as on tendons of the knees and elbows. Bilateral lesions consistent with xanthomas were seen on CT scan, that is, lesions on both sides of the body appeared to be xanthomas, according to the interpretation of the CT. The patient was treated with chenodeoxycholic acid; when this treatment was interrupted due to a case of diarrhea, treatment was resumed with lovastatin, another drug designed to reduce the level of cholesterol. The cholesterol sharply decreased, but the cholestanol did not. Treatment with another anticholesterol drug, simvastatin, resulted in cholesterol levels which were slightly higher than were achieved with lovastatin, but the patient's cholestanol level and the cholestanol/cholesterol ratio were reduced to within normal limits by simvastatin. This treatment was to no avail, however, and the patient died in 1988. The identification of this patient, however, led to the recognition that two of her sisters were also affected with the same genetic disorders. These two women had large Achilles tendon xanthomas and peripheral nerve damage. Both patients were placed on chenodeoxycholic acid and managed to achieve normal levels of cholesterol and cholestanol over the next few months. The first case illustrates that the normalization of cholesterol and cholestanol after considerable damage has already taken place is of little or no value for patients with CTX. The authors suggest that if this treatment is begun earlier, as in the case of the two sisters, it may be possible to arrest the development of the disease. (Consumer Summary produced by Reliance Medical Information, Inc.)