Impaired carbohydrate metabolism of polymorphonuclear leukocytes in glycogen storage disease Ib.

This study measures hexose monophosphate (HMP) shunt activity, glycolytic rate, and glucose transport in PMN and lymphocytes of patients with glycogen storage disease (GSD) type Ib as compared with controls and with GSD Ia patients. HMP shunt activity and glycolysis were significantly lower in intact PMN cells of GSD Ib patients as compared with GSD Ia patients and with controls. These activities were above normal levels in disrupted GSD Ib PMN. HMP shunt activity and glycolytic rates in lymphocytes were similar in all three groups studied. The rate of 2-deoxyglucose transport into GSD Ib PMN was 30% of that into cells of normal controls. In GSD Ib lymphocytes or in GSD Ia PMN and lymphocytes transport was normal. The striking limitation of glucose transport across the cell membrane of the PMN of GSD Ib patients may account for the impairment of leukocyte function that is characteristic of GSD Ib, but not found in GSD Ia patients.

Glucose and glycogen metabolism in erythrocytes from normal and glycogen storage disease type III subjects.

Active glycogen metabolism has been demonstrated in both normal and glycogen-rich erythrocytes taken from patients with type III glycogen storage disease. Activity of all enzymes catalyzing the reactions required for the synthesis and degradation of glycogen have been demonstrated in the mature erythrocytes. Uniformly labeled glucose-(14)C is incorporated into glycogen in intact cells of both types during incubation. Replacement of the glucose-(14)C by unlabeled glucose in the medium resulted in a significant loss of radioactivity from cellular glycogen. In the absence of the substrate a progressive shortening of outer branches occurred during incubation of intact glucogen-rich cells. Using cells from patients with type III glycogen storage disease, which have sufficient glycogen content to be analyzed by beta-amylolysis, we demonstrated that the glucosyl units are first incorporated in the outer tiers, then transferred to the core where they tend to accumulate due to the absence of amylo-1,6-glucosidase. The glycogen-rich cells have a more rapid rate of glucose utilization upon incubation which is not reflected by a higher lactate production. The increased rate of glucose utilization did not result from an increased rate of glucose incorporation into glycogen in affected cells. The rate of (14)CO(2) production from glucose-1-(14)C during incubation was not significantly different in the two types of cells unless methylene blue was added as an electron acceptor, in which case the glycogen-rich cells oxidized glucose to CO(2) more rapidly.

Effect of hydrocortisone and glucagon on glycogen metabolism in the fetal rat liver.

1. Hydrocortisone increases in vivo incorporation of [14C] glucose into fetal liver glycogen in the last days of gestation, whereas in glucagon-treated fetuses, a slight decrease in the incorporation rate was found. 2. Hydrocortisone increases total synthetase activity as that of synthetase a but was without effect on fetal liver glycogen phosphorylase. 3. Glucagon causes a slight increase in phosphorylase a activity on days 19-21, and was without effect on the activities of synthetase a and total synthetase. 4. Dibutyryl cyclic AMP had no effect on the key enzymes of glycogen metabolism 1 h after injection in utero, whereas after 6 h an increase in phosphorylase a activity was found without any change in synthetase a activity.

Growth and nutritional status of Bedouin infants in the Negev Desert, Israel: evidence for marked stunting in the presence of only mild malnutrition.

Growth and feeding practices of 353 Bedouin infants from the Negev Desert, Israel, were compared to those of 302 Jewish infants from the same area and to American standards. These two populations differed in their cultures and educational backgrounds. The use of medical and health services was lower among the Bedouin population. The feeding practices of the Bedouin infants were markedly different from those of their controls. The Bedouin infants show a progressive decrease in weight, length, and head circumference (means of all three parameters were around the 5th percentile) while the Jews were comparable to Americans. The nutritional status was assessed by three different anthropometric measurements. The weight to length ratio showed that 88% of Bedouin and 96% of Jewish infants were above the 10th percentile. Tricep skinfold measurements showed that 96% of the Bedouins and 99% of the Jews were above the 5th percentile. The midarm circumference to head circumference ratio was in the range between 0.280 and 0.310 (mild malnutrition range) while that of the Jews was above 0.310 (well-nourished range). These data show marked stunting in the presence of only mild malnutrition. This observation argues against the general belief that marked stunting is the result of prolonged severe malnutrition. Differences in cultural and genetic backgrounds, as well as different feeding practices and increased morbidity, could contribute to this phenomenon.

PIP: Growth and feeding practices of 353 Bedouin infants from the Negev Desert in Israel were compared to those of 302 Jewish infants from the same area and to American standards. These 2 populations differed in their cultures and educational backgrounds. The use of medical and health services was lower among the Bedouin population. Feeding practices of the Bedouin infants were markedly different from those of their controls. The Bedouin infants show a progressive decrease in weight, length, and head circumference (mean of all 3 parameters was around 5th percentile) while the Jewish children were comparable to Americans. The nutritional status was assessed by 3 different anthropometric measurements. The weight-to-length ratio showed that 88% of Bedouin and 96% of Jewish infants were above the 10th percentile. Tricep skinfold measurements showed that 96% of the Bedouin and 99% of the Jews were above the 5th percentile. The midarm circumference-to-head-circumference ratio was in the range between 0.280-0.310 (mild malnutrition range) while that of the Jews was above 0.310 (well-nourished range). These data show marked stunting in the presense of only mild malnutrition. This observation argues against the general belief that marked stunting is the result of prolonged severe malnutrition. Differences in cultrual and genetic backgrounds as well as different feeding practices and increased morbidity could contribute to this phenomenon.

Myophosphorylase deficiency: the course of an unusual congenital myopathy.

A 59-year-old man had proximal weakness and wasting that started in early childhood. EMG was "myopathic," serum CK activity was increased, and muscle biopsy showed accumulations of glycogen. Biochemical studies revealed elevated glycogen concentration and absence of myophosphorylase activity. This unusual presentation of a long-standing, painless, and quite static weakness due to myophosphorylase deficiency represents another example of clinical heterogeneity.

Adult muscle phosphorylase "b" kinase deficiency.

A 35-year-old man had severe exercise intolerance and cramps. Venous blood lactate did not rise after ischemic exercise, and electromyographically silent contracture of hand muscles appeared. Histochemistry and electronmicroscopy of a muscle biopsy revealed subsarcolemmal and intermyofibrillar accumulation of glycogen. Biochemical studies showed moderately increased amount of glycogen. Total phosphorylase activity was normal, but the active form "a" was 27% of normal. Phosphorylase kinase activity was 12% of the normal value and was normal in leukocytes and erythrocytes.

Dexamethasone and salbutamol in the treatment of acute wheezing in infants.

Thirty-two infants, aged 1 to 12 months, hospitalized with acute wheezing, were studied. They were randomly divided into four treatment groups of eight patients each. The treatments were intramuscular dexamethasone or placebo (double-blind), and salbutamol (oral and inhaled), or none (open), in all four possible combinations. The study was carried out as a randomized block design with eight blocks of four infants each, matched by age and clinical score. Average daily improvements, as reflected by changes in the clinical score and length of hospital stay, was essentially the same for infants treated with placebo, salbutamol alone, and dexamethasone alone. However, combined salbutamol-dexamethasone treatment resulted in more than twice the rate of improvement of the other treatments. The difference was statistically highly significant (P less than .01). Furthermore, the response of this combined treatment was observed within 24 hours; none of the ten infants in whom there was no significant improvement within 48 hours and neither of the two patients who developed respiratory failure received the combined salbutamol-dexamethasone treatment. A potentiating effect of corticosteroids on the beta-adrenergic responsiveness is a possible explanation for the advantage of this combined treatment in the management of acute wheezing in infancy.

Glycogen storage disease type 1a in Israel: biochemical, clinical, and mutational studies.

Glycogen storage disease type 1a (von Gierke disease, GSD 1a) is caused by the deficiency of microsomal glucose-6-phosphatase (G6Pase) activity which catalyzes the final common step of glycogenolysis and gluconeogenesis. The recent cloning of the G6Pase cDNA and characterization of the human G6Pase gene enabled the characterization of the mutations causing GSD 1a. This, in turn, allows the introduction of a noninvasive DNA-based diagnosis that provides reliable carrier testing and prenatal diagnosis. In this study, we report the biochemical and clinical characteristics as well as mutational analyses of 12 Israeli GSD 1a patients of different families, who represent most GSD 1a patients in Israel. The mutations, G6Pase activity, and glycogen content of 7 of these patients were reported previously. The biochemical data and clinical findings of all patients were similar and compatible with those described in other reports. All 9 Jewish patients, as well as one Muslim Arab patient, presented the R83C mutation. Two Muslim Arab patients had the V166G mutation which was not found in other patients' populations. The V166G mutation, which was introduced into the G6Pase cDNA by site-directed mutagenesis following transient expression in COS-1 cells, was shown to cause complete inactivation of the G6Pase. The characterization of all GSD 1a mutations in the Israeli population lends itself to carrier testing in these families as well as to prenatal diagnosis, which was carried out in 2 families. Since all Ashkenzai Jewish patients harbor the same mutation, our study suggests that DNA-based diagnosis may be used as an initial diagnostic step in Ashkenazi Jews suspected of having GSD 1a, thereby avoiding liver biopsy.

Permanent tetraplegia as a consequence of tetanus neonatorum. Evidence for widespread lower motor neuron damage.

It is generally believed that no permanent neurological damage is found among survivors of tetanus neonatorum. Newborns dying shortly after the onset of tetanus also lack significant neurological abnormalities. In adults a variety of neuromuscular lesions have been reported; however, a uniform pathological picture is absent. We report a case of a newborn with severe tetanus in whom striking evidence of anterior horn neuronal damage was documented, causing permanent nonprogressive tetraplegia. We suggest that the mechanism responsible for this lesion involves the retrograde axoplasmic flow of tetanus toxin reaching the spinal cord via nerve endings in the infected umbilical cord stump.

Criteria map audit of scorpion envenomation in the Negev, Israel.

A criteria map audit is a medical record audit in which quality of care is evaluated according to algorithmically arranged criteria. Thus, a particular criterion is applied to the patient record only if other criteria have been met. For example, if a stung child's condition is severe but not life threatening and if he has had a positive skin test for antivenom sensitivity then he should receive antivenom only after receiving adrenaline and hydrocortisone. We used a modified criteria map audit to determine both the clinical picture of scorpion envenomation and quality of care process in 94 children. Related outcomes of care measured included mortality, persistent morbidity, allergic reaction to scorpion antivenom and length of stay in hospital. Scorpion stings in the Negev region are usually due to the yellow scorpion, L. quinquestriatus, and usually occur in the summer months on the extremities in exposed male children under 10. The clinical picture is more severe when the scorpion is yellow, when the child is younger and when the sting is on the trunk or head. Symptoms apparently mediated by the central nervous system (2.6 findings/child) were more frequent than parasympathetic symptoms (2.3 findings/child). Treatment with antivenom and specific therapy for complications led to very low persistent morbidity and mortality in symptomatic cases, but was also accompanied by a longer hospital stay (64% equal to or greater than 3 days) than for asymptomatic cases (18% equal to or greater than 3 days). Testing for antivenom sensitivity was omitted in an unacceptably high percentage of cases (69%) and its omission led to an allergic reaction in 4 out of 40 cases (10%). Inadequacy in treatment of 7 secondary clinical problems ranged from 71% for hypertension to 29% for seizures (mean 46%). Persistent morbidity was negligible and mortality was 1.2%. We conclude that criteria map audit can be used to describe the clinical and epidemiological picture of a clinical problem while at the same time providing an audit of the process of care.

Neurophysiologic studies in congenital insensitivity to pain with anhidrosis.

Thirteen patients with congenital insensitivity to pain and anhidrosis, carrying a mutation at the TRK-A gene, were studied. Neurologic examination revealed vestigial pain sensitivity, suggesting an incomplete involvement of the affected nerves. All 13 patients manifested normal electrophysiologic studies but striking absence of sympathetic skin responses. We suggest the use of the sympathetic skin response test in the clinical evaluation of patients suspected of having congenital insensitivity to pain and anhidrosis.