O. Giardini

Abnormal intestinal permeability in children with autism

We determined the occurrence of gut mucosal damage using the intestinal permeability test in 21 autistic children who had no clinical and laboratory findings consistent with known intestinal disorders. An altered intestinal permeability was found in 9 of the 21 (43%) autistic patients, but in none of the 40 controls. Compared to the controls, these nine patients showed a similar mean mannitol recovery, but a significantly higher mean lactulose recovery (1.64%± 1.43 vs 0.38%±0.14; P < 0.001). We speculate that an altered intestinal permeability could represent a possible mechanism for the increased passage through the gut mucosa of peptides derived from foods with subsequent behavioural abnormalities.

Low serum tryptophan to large neutral amino acids ratio in idiopathic infantile autism.

The serum tryptophan to large neutral amino acids ratio (Try/LNAA) is considered a reliable marker of tryptophan availability for brain serotonin synthesis. A dysfunction of brain serotonergic activity has been postulated to exist in autistic disorder and supported by recent studies. On this basis, we determined the serum amino acids levels in 40 children with idiopathic infantile autism as well as in 46 control children. A significantly lower serum Try/LNAA ratio was observed in the autistic subjects compared to the normal controls. In 14 autistic children (35%) this ratio was 2 SD below the mean value obtained in the control group. These results suggest that a low brain tryptophan availability due to a low serum Try/LNAA ratio could be one of the possible mechanisms involved in the alteration of serotonergic function in autism.

Usefulness of cyanide-nitroprusside test in detecting incomplete recessive heterozygotes for cystinuria: a standardized dilution procedure

Abstract We present the results of a cyanide-nitroprusside test (CNT) after a standardized dilution procedure of urine samples and report the efficiency of this method in detecting heterozygotes for cystinuria when applied on an open pediatric population. In the preliminary study we assayed by quantitative determination of amino acids 162 urine samples from a hospital population identifying 24 type III heterozygotes and 2 type II heterozygotes for cystinuria. The classic CNT gave 38 false positive results and 5 false negative results showing a sensitivity and specificity of 0.808 and 0.721, respectively. When progressively diluted, all samples of heterozygotes remained CNT positive up to a creatinine concentration of 90 mg/dl. At this level of dilution 31 out of 38 false positive turned to negative, thus obtaining a specificity of 0.922 without a lowering of the sensitivity in detecting heterozygotes. The standardized dilution at 90 mg/dl of creatinine concentration was applied to 74.7% of a population of 1024 schoolchildren. In this way 163 out of 210 positive results were eliminated and thus the specificity of CNT rose from 0.789 to 0.953. On the basis of these results, the method proposed can be regarded as reliable and useful for a␣screening program in detecting heterozygotes for cystinuria.

Adenylosuccinase deficiency: a patient with impaired erythrocyte activity and anomalous response to intravenous fructose

SummaryClinical and biochemical data are presented on an Italian patient with adenylosuccinase deficiency of both erythrocytes and mixed peripheral blood lymphocytes. The erythrocyte enzyme showed normal substrate affinity, but decreased thermal stability. The patient displayed an anomalous response to an intravenous fructose tolerance test with a rise in plasma [Mg2+] and [K+] and a drop in plasma levels of inorganic phosphate, glucose, urate and succinylnucleosides upon fructose injection.

Ciguatera Fish Poisoning: An Emerging Syndrome in Italian Travelers

Ciguatera is an acute or chronic intoxication syndrome associated with the consumption of marine tropical reef fish. The illness has a short incubation period, and the symptoms typically affect the gastrointestinal and nervous systems. Ciguatera poisoning has been extensively reviewed. 1‐5 It is endemic in many tropical and subtropical regions, also in the United States, 5,6 and Mexico, 7 where it accounts for more than half of all outbreaks related to ingestion of fish. In the Caribbean and Indo-Pacific islands, regions where coral reefs are present, the disease is the most common seafood-borne illness.Ciguatera poisoning can occur after the consumption of a wide variety of predatory tropical fish including barracuda,surgeon fish,red-snapper,amber-jack,red-grouper, and king-mackerel. These fish contain heat resistant and acid-stable toxins, mainly ciguatoxin, a lipid-soluble toxin, and maitotoxin, a water-soluble toxin. Both poisons belong to a newly described class of toxins, chemically polycyclic ether compounds, produced by tropical marine microalgae that become attached to the epiphytes of macroalgae, which herbivorous fish consume while foraging. Many small fish succumb to ciguatoxin and are eaten by other fish. Hence ciguatera toxin becomes more bioconcentrated as it passes up through the food chain from large carnivorous fish to larger predatory reef fish and ultimately to humans. Whereas the toxins are harmless in the host fish, in humans they produce illness. The earliest and commonest symptoms to appear are watery diarrhea, nausea and vomiting, abdominal pain, typically lasting about 12 hours. Usually, 24‐48 hours after ingesting the toxic fish, neurologic symptoms follow, including numbness, lip, tongue, and limb paresthesias, severe itching, and cold-to-hot temperature reversal (considered a pathognomonic sign). The illness generally subsides within a week. Neurologic symptoms may last for months or subside and then recur. Prompted by the growing number of Italian travelers returning from the Caribbean who present to our unit after experiencing symptoms of ciguatera poisoning, we designed this clinical study to assess the clinical outcome in our patients.We also sought to know whether they had received information before departure on the potential risks of ciguatera fish poisoning. Methods

Determination of urinary orotic acid and uracil by capillary zone electrophoresis.

We describe a simple method for measuring orotic acid and uracil concentration in urine by capillary zone electrophoresis in 20 mM Na-borate buffer, pH 9.2. The method was applied for studying a patient with HHH (hyperomithinemia, hyperammonemia and homocitrullinuria) syndrome. A high value of uracil excretion was found during periods of relatively low orotic acid excretion and normal ammonemia. The orotic acid level in urine was increased by increasing protein intake.

Amoxycillin and clavulanic acid in the treatment of urinary tract infections in children

The efficacy of amoxicillin–clavulanic acid combination in the treatment of urinary tract infections resistant, in vitro, to amoxycillin was studied in 42 children. Of the 24 children with urinary tract infection for the first time, combination therapy, dosing twice daily for 5 days (40 mg/kg·day), cleared the infection in 23 (96%) cases. Relapse occurred in four (17%) cases within 30 days. Of the 18 children who presented with recurrent urinary tract infections therapy, as above, cleared the infection in 16 (89%) cases. In these cases, long-term therapy was performed at a dosage of 20 mg/kg once daily. Tolerance was good; gastro-intestinal disorders in five (12%) cases which regressed by dosing at 8 h rather than 12 h intervals. In conclusion, amoxycillin–clavulanic acid can be considered a first choice treatment of urinary tract infections in children.

Erythrocyte membrane lipid peroxidation before and after vitamin E supplementation in children with cholestasis

In 10 children with chronic cholestasis and without neurologic signs, we evaluated lipid peroxidation and vitamin E levels in serum and in the erythrocytes before and after a therapeutic trial with alpha-tocopherol. We also studied the effects of vitamin E administration on hematocrit and hemoglobin values and on reticulocyte and erythrocyte counts. Plasma and erythrocyte malonyldialdehyde (MDA) values were significantly higher compared with normal control values, whereas plasma and erythrocyte tocopherol measurements were lower. Oral administration of high doses of vitamin E (300 mg/day for 15 days) resulted in lower serum MDA levels, whereas serum vitamin levels did not change significantly. In erythrocytes, the MDA decreased but not to control levels, and vitamin E increased but to lower values than normal. Hematologic values also improved. We conclude that longer treatment might be necessary to completely reverse the oxidative damage associated with vitamin E deficiency in children with cholestasis.

Effect of D-Ribose Administration to a Patient with Inherited Deficit of Adenylosuccinase

Adenylosuccinase (EC 4.3.2.2; ASase) deficiency is a newly discovered inborn error of metabolism that involves the purine de novo pathway and results in the accumulation of dephosphorylated substrate derivatives of the defective enzyme, namely succinylaminoimidazole carboxamide (SAICA) riboside and succinyladenosine (S-Ado).1–3 Although substantial progress has been made regarding our knowledge of the inherited disease, including its characterisation at gene level,4–5 much work remains to be done, particularly with respect to the mechanisms whereby the defect exerts its deleterious effects on brain function.

Autoimmune thyroiditis in a case of tyrosinaemia type III

Agamanolis DP, Potter JL, Naito HK, Robinson HB, Kulasekaran T (1986) Lipoprotein disorder, cirrhosis and olivopontocerebelIar degeneration in two sibiings. Neurology 36: 674-681. Harding BH, Dunger DB, Grant DB, Erdohazi M (1988) Familial olivopontocerebellar atrophy with neonatal onset: a recessively inherited syndrome with systemic and biochemical abnormalities. J Neurol Neurosurg Psychiatr 51: 385-390. Horslen SP, Clayton PT, Harding BN, Halt NA, Keir G, Winchester BG (1991) Olivopontocerebellar atrophy of neonatal onset and disialotransferrin developmental deficiency syndrome. Arch Dis. Child 66: 1027-1032. Jaeken J (t989) Disialotransferrin developmental deficiency and olivopontocerebellar atrophy. Arch Dis Child 64: 764-765. Jaeken J, Stibler H, Hagberg B (1991) The carbohydrate-deficient glycoprotein syndrome. Acta Paediatr, Scan& Suppl. 375: [monograph].