Adenylosuccinate lyase deficiency in a Malaysian patient, with novel adenylosuccinate lyase gene mutations.

Most cases of adenylosuccinate lyase (ADSL OMIM 103050) deficiency reported to date are confined to the various European ethnic groups. We report on the first Malaysian case of ADSL deficiency, which appears also to be the first reported Asian case. The case was diagnosed among a cohort of 450 patients with clinical features of psychomotor retardation, global developmental delay, seizures, microcephaly and/or autistic behaviour. The patient presented with frequent convulsions and severe myoclonic jerk within the first few days of life and severe psychomotor retardation. The high performance liquid chromatography (HPLC) profile of the urine revealed the characteristic biochemical markers of succinyladenosine (S-Ado) and succinyl-aminoimidazole carboximide riboside (SAICAr). The urinary S-Ado/SAICAr ratio was found to be 1.02 (type I ADSL deficiency). The patient was compound heterozygous for two novel mutations, c.445C > G (p.R149G) and c.774_778insG (p.A260GfsX24).

Early recovery of the actin cytoskeleton during renal ischemic injury in vivo.

The actin cytoskeleton of proximal tubule cells is important for both the maintenance of membrane domains and attachment to neighboring cells and underlying substrata. Adenosine triphosphate (ATP) depletion during ischemic injury causes early alterations in the actin cytoskeleton, resulting in loss of membrane domains and cellular attachment. We examined the actin cytoskeleton during recovery from ischemic injury. As shown previously in cell culture studies, ATP depletion to 14% of control values from in vivo ischemia resulted in decreases in G-actin consistent with net polymerization of the cytoskeleton. After 20 minutes of recovery restored ATP levels to 24% of control values, percent G-actin increased back to control values, yet cytoplasmic actin polymerized with little evidence of apical recovery. After 120 minutes of recovery, ATP levels had increased to 48% of control values with little qualitative or quantitative change in actin polymerization from 20 minutes of recovery. When ATP levels recovered to 65% of control values at 360 minutes after ischemia, movement of F-actin back toward the apical surface was observed. These data, along with prior data using maleic acid, suggest that thresholds of cellular ATP may cause differing effects on distinct cellular actin pools. We conclude that actin cytoskeletal recovery occurs very early and may be necessary for reestablishment of polarity essential for normal reabsorptive functions.

High energy phosphate depletion in leaflet matrix cells during processing of cryopreserved cardiac valves.

Preimplantation preparation of cardiac valves includes three major steps: (1) harvesting with accompanying ischemia (warm time from cessation of donor heart beat), (2) antibiotic disinfection, and (3) controlled-rate cryopreservation. To define the interdependent injury effects of these manipulations on leaflet matrix cells and specifically the potential for prolonged harvest-related ischemia to predispose greater injury by the subsequent steps, 96 semilunar valves were harvested from pigs in a manner analogous to human heart valve retrievals and randomly allocated to study groups as follows: 48 control valves were exposed to increasing harvested-related ischemic times, (2, 6, 12, 24 hr) and immersed in liquid nitrogen to arrest metabolic activity (i.e., prior to cryopreservation) and conclude the ischemia; another 48 were similarly harvested, subjected to identical ischemic times, then disinfected in 4 degrees C RPMI medium with standard antibiotics for 24 hr and dimethylsulfoxide cryopreserved at -1 degrees C/min to -170 degrees C (i.e., formal cryopreservation protocol). At thawing, each valve was extracted in 12% trichloroacetic acid and assayed by high performance liquid chromatography for components of the adenine nucleotide pool including ATP, lower energy nucleotides (total adenine nucleotides, [TAN] = [ATP] + [ADP] + [AMP]), adenosine, and the diffusible purines. Results are reported as nanomoles metabolite/milligram of leaflet cell protein (Lowry) and reflect a maintenance of total high energy phosphates in the control groups (5.41 +/- 0.29 nmole TAN at 2 hr; 8.34 +/- 0.67 nmole TAN at 24 hr), which fell significantly in all cryopreserved groups (1.27 +/- 0.33 nmole TAN at 2 hr; 0.34 +/- 0.22 nmole TAN at 24 hr).(ABSTRACT TRUNCATED AT 250 WORDS)

[Muscular diseases: epidemiology of progressive muscular dystrophies]. / Malattie muscolari: l'epidemiologia delle distrofie muscolari progressive.

Epidemiology of muscular dystrophies has been important in the prevention of these diseases. In fact the genetic counselling, after a preliminary epidemiological investigation, reduced the incidence rate of Duchenne muscular dystrophy in the Veneto Region. Furthermore the new biochemical data on dismetabolic muscular diseases revealed a future strategy in the early identification of muscular dystrophies for their epidemiology and genetic prevention as well as for the new systems of research used in the field of muscular dystrophies.

Acquired storage pool deficiency with increased platelet-associated IgG. Report of five cases.

Acquired abnormalities of platelet aggregation have been reported with increasing frequency. We studied five patients (including two with systemic lupus erythematosus and one with compensated chronic idiopathic thrombocytopenic purpura) in whom platelet aggregation responses to collagen, epinephrine and ADP are impaired; in all cases, we found that levels of platelet-associated immunoglobulin G (IgG) were increased. In all five patients substances stored in platelet-dense granules (ATP, ADP, serotonin and calcium) were diminished. The content of the alpha-granule substance, beta-thromboglobulin, was also decreased in most cases, whereas the levels of two secretable acid hydrolase enzymes (beta-glucuronidase and beta-N-acetyl glucosaminidase) were within normal limits. These findings are similar to those observed in subtypes of congenital storage pool deficiency. However, in contrast to the congenital disorder, a membrane-bound (nonsecretable) acid phosphatase was also decreased in the patients with acquired storage pool deficiency. These findings suggest that impaired platelet aggregation on an acquired basis may, in some patients, be due to immune platelet damage resulting in a distinctive type of platelet storage pool deficiency.