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Hereditary tyrosinemia results from an inborn error in the final step of tyrosine metabolism. The disease is known to cause acute and chronic liver failure, renal Fanconi's syndrome, and hepatocellular carcinoma. Neurologic manifestations have been reported but not emphasized as a common problem. In this paper, we describe neurologic crises that occurred among children identified as having tyrosinemia on neonatal screening since 1970. Of the 48 children with tyrosinemia, 20 (42 percent) had neurologic crises that began at a mean age of one year and led to 104 hospital admissions. These abrupt episodes of peripheral neuropathy were characterized by severe pain with extensor hypertonia (in 75 percent), vomiting or paralytic ileus (69 percent), muscle weakness (29 percent), and self-mutilation (8 percent). Eight children required mechanical ventilation because of paralysis, and 14 of the 20 children have died. Between crises, most survivors regained normal function. We found no reliable biochemical marker for the crises (those we evaluated included blood levels of tyrosine, succinylacetone, and hepatic aminotransferases). Urinary excretion of delta-aminolevulinic acid, a neurotoxic intermediate of porphyrin biosynthesis, was elevated during crises but also during the asymptomatic periods. Electrophysiologic studies in seven patients and neuromuscular biopsies in three patients showed axonal degeneration and secondary demyelination. We conclude that episodes of acute, severe peripheral neuropathy are common in hereditary tyrosinemia and resemble the crises of the neuropathic porphyrias.

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SUMMARY Bile acid loss (mg/M2 24h) in the stools of 43 cystic fibrosis (CF) children with pancreatic insufficiency was 751 1 + 48-3, while that of six without clinical evidence of pancreatic disease (133.4 15 9) did not differ from values in 25 controls (109.8 ± 9.8). There was a good correlation between the degree of bile acid (BA) and fat sequestration. Concomitant changes in bile acid and fat loss were observed in one group of six patients studied on and off pancreatic enzymes as well as in a second group of seven children treated with pancreatic supplements and maintained on a normal diet followed by a low fat diet supplemented with medium chain triglycerides. Administration of NA bicarbonate led to a significant decrease in fat loss (15-8 ± 2-7 -* 103 1 9) without any simultaneous change in bile acid excretion (533-1 ± 58-3 --500 4 ± 58 6). Qualitative bile acid patterns in controls, in infants after an ileal resection, and in patients with CF or with coeliac disease showed that the percentage of primary BA followed closely the total amount excreted except in situations where antibiotics were administered. The exact mechanism for the increased loss of BA in CF is unknown. It is found in all age groups and is related to the presence and degree of pancreatic insufficiency. The possibility that unhydrolysed triglycerides may interfere with the intestinal absorption of bile acid needs further confirmation.

's Ilosp, London. studies wcre undertaken to assess the value of including base in ORS in (i) an animal model of intestinal secretion and (ii) children with acutc gastroenteritis. After exposure to cholera toxin, rat small intestine was perfused in situ with ORS containing base or identical OR5 in which base was replaced by chloride.

Because of the increased incidence of gallstones in cystic fibrosis we compared biliary lipid composition in 26 patients with cystic fibrosis, seven children with cholelithiasis but no cystic-fibrosis and 13 controls. Eighteen of the cystic fibrosis group had cholecystograms, and only one had gallstones. In 14 patients with cystic fibrosis who had stopped taking pancreatic enzymes for one week molar percentage of lipid composition accounted for by cholesterol (mean +/- S.E., 16.3 +/- 2.9) and saturation index (2.0 +/- 0.3) were comparable to values of the cholelithiasis group and higher (P less than 0.01) than those of controls. In 12 patients with cystic fibrosis taking pancreatic enzymes, molar percentage of cholesterol (8.6 +/- 1.7) and saturation index (1.0 +/- 0.1) did not differ from those of controls; in cystic fibrosis there was a preponderance of cholic over chenodeoxycholic acid both off (1.7 +/- 0.2) and on (1.9 +/- 0.3) therapy as compared to the cholelithiasis (0.7 +/- 0.1) and control (0.8 +/- 0.0) groups. The glycine/taurine ratio of conjugated bile acids were lower in enzyme-treated patients with cystic fibrosis (3.7 +/- 0.6) than in patients off treatment (6.4 +/- 1.0), but was higher (P less than 0.01) than in controls (1.8 +/- 0.2). Bile is lithogenic in untreated cystic fibrosis and responds to pancreatic enzymes.

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