Mannosidosis in three brothers--a review of the literature.

Three brothers with mannosidosis were studied, and their clinical and biochemical manifestations are compared with those of 41 cases in the literature. All three boys have psychomotor and growth retardation, characteristic facies, recurrent respiratory infections, sensorineural deafness, craniosynostosis, protuberant abdomens, and thin limbs. Roentgenographic findings of mild dysostosis multiplex, thick calvaria, abnormally contoured vertebrae, coarse trabeculi and thin cortices are consistent with those of reported cases. The lymphocytes of peripheral blood and bone marrow are vacuolated. Alpha-mannosidase deficiency in leukocytes and cultured skin fibroblasts and glycoproteinuria have been documented. The biochemistry of this glycoproteinosis and the pitfalls in diagnosis, such as improper assay conditions of pH and substrate concentration, are discussed. Extrapolation of in vitro and animal model studies suggest that trace metal therapy may be more effective than attempts at enzyme replacement to treat this hereditary storage disease.

Juvenile-onset metachromatic leukodystrophy: biochemical and electrophysiologic studies.

A 15-year-old girl with juvenile-onset metachromatic leukodystrophy (MLD) had markedly decreased leukocyte arylsulfatase A activity and low levels of leukocyte beta galactosidase and serum acid phosphatase. There was marked slowing of nerve condition velocity, and metachromasia was seen in biopsied sural nerve. Leukocyte arylsulfatase A activity was decreased in all members of the girl's family, and sural nerve action potentials were abnormal in two asymptomatic siblings. Electrophysiologic studies combined with biochemical studies may aid in the identification of presymptomatic metachromatic leukodystrophy homozygotes or asymptomatic heterozygotes.

Selenium supplementation in low-birthweight premature infants: relationship to trace metals and antioxidant enzymes.

We attempted to study the effect of selenium supplementation upon trace metal metabolism in low-birthweight infants less than 1000 g birthweight. Serum levels of the trace metals copper, zinc, and selenium; and white blood cell glutathione peroxidase (GSH-Px) and superoxide dismutase (SOD) activities were measured in conjunction with the trace metals when parenteral nutrition (TPN) was begun (sample A), at the initiation of enteral nutrition (sample B), and when TPN was discontinued (sample C). Two randomly selected groups of infants were evaluated: group S received selenium supplementation (1.34 micrograms/kg per d) in their parenteral nutrition solutions; group C was a control which did not receive selenium supplementation. Selenium levels declined to equally low levels in both groups by sample C, but were significantly higher in group S at sample B. GSH-Px activities demonstrated a significant increase at sample B in group S and then tended to decrease. In group C, GSH-Px tended to increase, then decreased significantly by sample C. Both groups received 20 micrograms/kg per d of copper in TPN, however, serum copper declined significantly at sample B in group S whereas there were no significant changes in group C. There were no significant changes in zinc and SOD levels. There were no significant differences between groups in clinical characteristics or outcome. This study suggests that a dose of supplemental selenium of 1.34 micrograms/kg per d in TPN is inadequate for low-birthweight premature infants. Selenium supplementation may also affect copper metabolism.

Ca2+ release mechanism of primate drug-induced coronary vasospasm.

Cellular mechanisms of protection against drug-stimulated coronary vasospasm were studied by multiweek estrogen plus progesterone (P) vs. medroxy-progesterone acetate (MPA) treatments by measuring intracellular Ca2+ and protein kinase C (PKC) signals. Ovariectomized monkeys (OVX) were treated by slow-release implants with either P or MPA for 4 wk added to estradiol-17 beta (E2) begun 2 wk earlier. A third group received E2 for 2 wk and withdrawal of E2 (W; no steroid treatment) during the last 4 wk. OVX coronary artery vascular muscle cells (VMC) in primary culture conditions were labeled by the fluorescent indicators, fluo 3 and hypericin, respectively, to study intracellular Ca2+ and PKC mechanisms of coronary artery hyperre-activity, using digital analysis of single VMC by photon-counting camera. Stimulation by 10 microM serotonin and 100 nM U-46619 (thromboxane A2 mimetic) caused Ca2+ increases (2-5 min) and no PKC activation in VMC from five P-treated monkeys but prolonged (> or = 30 min) increases in both Ca2+ and PKC signals in VMC from six MPA-treated monkeys or seven W-treated monkeys; these P vs. MPA (or W) differences were maintained > or = 14 days. We hypothesize that hyperreactivity in VMC from MPA- or W-treated monkeys results from accelerated prolonged Ca2+ release, with concomitant PKC activation, and that MPA (but not P) negates the coronary vasospasm protective effect of E2.

Serum hexosaminidase activity in I-cell disease carriers.

Serum heat stable hexosaminidase activities are used to identify 47-I-cell disease heterozygotes in a large kindred. Serum beta-hexosaminidase isozyme patterns in normal individuals, Tay-Sachs disease carriers, I-cell disease carriers and in cord blood samples are compared.

Brain dysfunction in an adolescent with the neuromuscular form of hexosaminidase deficiency.

A 14-year-old girl of Ashkenazi Jewish background is described who has severe deficiency of hexosaminidase A. She presented with slowly progressive motor neuron degeneration and was found to have subtle deficiencies on neuropsychological testing, abnormal cortical evoked potentials and structural abnormalities of the cerebellum on CT scan. This patient extends the reported clinical findings for adolescents and suggests the possibility of similar abnormalities in others with neuromuscular deterioration.

Alpha-fetoprotein and acetylcholinesterase in twins discordant for neural tube defect.

Twins concordant for elevated alpha-fetoprotein (AFP) and acetylcholinesterase (AChE) and discordant for neural tube defect (NTD) and sex are reported. A literature review reveals instances of termination of twin pregnancies with one normal and one abnormal fetus, partly based on concordant high AFP and positive AChE (although discordant on ultrasound examination). The levels of AFP and AChE in twin pregnancies are probably a function of the number of layers of fetal membranes separating twin sacs; dichorionic, diamniotic membranes allow transfer of AFP; monochorionic, diamniotic membranes allow transfer of both AFP and AChE. Cautious interpretation of biochemical findings and reliance on high resolution ultrasonography are suggested.

Enzymatic basis of typical X-linked icthyosis.

Steroid sulphatase activity was determined in cultured fibroblasts from 25 individuals with X-linked ichthyosis from four countries. All those with X-linked disease had markedly reduced enzyme levels compared with controls and patients with other types of ichthyosis. X-linked ichthyosis seems to be the result of a common mutation affecting the expression of steroid-sulphatase activity.

Placental steroid deficiency: association with arylsulfatase A deficiency.

A family with an obstetric history consistent with placental sulfatase deficiency has X-linked ichthyosis. Steroid sulfatase deficiency was confirmed in placenta, leukocytes, and cultured skin fibroblasts of affected males; arylsulfatase A diminution was also observed in these tissues of both affected males and 2 generations of related females. No symptoms of metachromatic leukodystrophy are present in any family members. In this family, placental sulfatase deficiency, and arylsulfatase A pseudodeficiency are nonallelic.