Tay-Sachs Disease with Altered β-Hexosaniinidase B: A New Variant?

Abstract

SummaryA 2.5-year-old Japanese girl who showed signs and symptoms compatible with classic Tay-Sachs disease and had 'altered P-. hexosaminidase B and I, a s well as completely deficient Phexosaminidase A activity is reported herein.Heat treatment of the patient's serum and leukocyte samples showed the existence of 13.5-27.3% and 35.7% of the heatlabile component of P-hexosaminidase, respectively, such is usually considered to correspond to /3-hexosaminidase A. The absence of Phexosaminidase A activity was confirmed by DEAE-cellulose column chromatography and cellulose acetate paper electrophoresis. The patient's serum P-hexosaminidase also contained a significant amount of acid pH-labile components. The effects of buffer concentrations on the activities of total and heat-labile components of the serum P-hexosaminidase of the patient differed from those of the control subjects.Heat treatment of the each component of serum phexosaminidase which had been separated by DEAE-cellulose column chromatography showed that P-hexosaminidase B and I, in the serum from this patient were heat labile as compared with those from the control subjects, and the other component I, was less heat labile at 50" for 3 h.There were no differences in the k, values of P-hexosaminidase B, I,, and I, for the synthetic substrate 4-methylumbelliferyl N-acetyl-P-D-glucosaminide before and after heat treatment at 50" for 3 h among the reported patient, another patient with classic Tay-Sachs disease, and a normal infant. SpeculationIn prenatal diagnosis of such patients as reported herein, it will be necessary to confirm the absence of P-hexosaminidase A in amniotic fluid and/or amniotic fluid cells by methods other than the heat-inactivation method, e.g., electrophoresis o r ionexchange column chromatography.Tay-Sachs disease (TSD) is a lysosomal storage disease inherited in an autosomal recessive manner. The gene frequency is extremely high in the Jewish population, but sporadic cases have been reported from various other populations including the Japanese.In 1969, Okada and O'Brien (13) did starch-gel electrophoresis studies and found that one of two isozymes of N-acetyl P-D-hexosaminidase (Hex), Hex A , was absent in brain, liver, kidney, skin, cultured skin fibroblasts, blood plasma, and leukocytes from TSD patients. In 1970, O'Brien et al.(1 1) reported a heat-inactivation method for serum Hex A determination with the synthetic substrate 4-methylumbelliferyl N-acetyl-P-Dglucosaminide and its application to the detection of TSD heterozygotes and homozygotes. Since that time, the heat-inac-. tivation method has been used for the detection of TSD patients, its carriers, and patients with partial Hex A deficiency. Patients with partial Hex A deficiency are distinguishable from those with ciassic TSD as the onset is later and the course milder (2, "14, 23, 28). We encountered a Japanese girl who showed signs and symptoms compatible with classic TSD. Hex A activities in serum samples, as detected by the heat-inactivation method, revealed partial ...

ULTRASTRUCTURAL PATHOLOGY OF SKIN BIOPSY AND FIBROBLAST ENZYME STUDIES IN A CASE OF GM2-GANGLIOSIDOSIS WITH DEFICIENT HEXOSAMINIDASE A AND THERMOLABILE HEXOSAMINIDASE B

“…The latter finding may explain the high (21 %) residual heat-labile hexosaminidase activity found when using the heat inactivation test for hexosaminidase A. We may, therefore, deal with a disorder affecting hexosaminidase B additionally to but in another way than hexosaminidase A (Momoi et al 1978, Lane and ]enkins 1978). The parent's serum hexosaminidase values would also be compatible with such a mixed genotype.…”

Tay-Sachs Disease Carrier Screening: A Model for Prevention of Genetic Disease

“…Although rare, they are of practical relevance because they affect specificity and sensitivity: (i) A number of HEXB alíeles produce a thermolabile Hex B enzyme. In some instances these alíeles are associated with a Gm2 gangliosidosis, i.e., a variant form of Sandhoff disease (Lane and Jenkins, 1978;Momoi et al, 1978;Lowden, 1979a); in others they appear to be benign (Hechtman and Rowlands, 1979;Navon et al, 1981a). In Israel, 0.6% of screened "carriers" have thermolabile hexosaminidase B (Peleg and Goldman, 1994).…”

Thermal activation of hexosaminidase A in a genetic compound with Tay‐Sachs disease

“…(11); an obligate heterozygote for TSD (©); a normal control (0) indeed heat-stable and remains virtually unchanged throughout this thermal treatment. Some cases with heat labile Hex B coexisting with deficient Hex A have been reported (Momoi et al, 1978;Navon et al, 1981). The occurrence of these presumed two distinct Hex mutations (~ and [3 chains) in the same individuals as well as isolated heterozygous or homozygous state for the mutant 13-chain allele make the conventional heat inactivation method unreliable.…”