Prenatal diagnosis of lamellar ichthyosis by direct mutational analysis of the keratinocyte transglutaminase gene.

Autosomal recessive lamellar ichthyosis (LI) is a rare inherited disease of cornification of the skin. Recently, the gene responsible for type I LI has been identified and mutations have been described. The identification of mutations in families at risk for LI allows a precise and rapid prenatal diagnosis. A family with a previously unreported mutation is described and a prenatal diagnosis based on a simple polymerase chain reaction (PCR) approach is outlined. The molecular diagnosis was confirmed on post-mortem examination of the skin.

Disseminated histoplasmosis in an adopted infant from El Salvador.

UNLABELLED: An HIV-negative 4-month-old infant recently adopted from El Salvador was admitted for high fever. Hepatosplenomegaly, anaemia, leucopenia, thrombocytopenia, increased transaminases, and diffuse interstitial pulmonary infiltration were present on admission. Granulomas were seen in bone marrow and liver biopsies without any organism. Disseminated histoplasmosis was diagnosed 2 weeks later when bone marrow and blood cultures taken on admission became positive for Histoplasma capsulatum and when histoplasmic antigen was detected in blood. The outcome was good after treatment with amphotericin B followed by itraconazole which was administered for a 6-month period without significant toxicity. CONCLUSION: Disseminated histoplasmosis is very rarely seen in Europe but should be suspected in case of unexplained fever in immigrants from the endemic areas in the world, particularly when hepatosplenomegaly and pancytopenia are present. Bone marrow examination and culture, blood cultures, and antigen testing are the mainstays of the diagnosis.

Chronic metabolic alkalosis in an infant with cystic fibrosis.

A 6-month-old infant suffering from cystic fibrosis is reported. In spite of an apparently appropriate treatment and in absence of respiratory infection, the patient showed progressive anorexia, intermittent vomiting and weight loss. These non-specific signs and symptoms could all be explained by metabolic alkalosis and disappeared immediately after oral supplementation with sodium and potassium chloride. This unusual metabolic complication should be searched for in every cystic fibrosis infant with unexplained anorexia and failure to thrive.

Anti-liver-kidney microsome antibody-positive autoimmune hepatitis associated with alopecia.

A 14-year-old girl presented with anti-liver-kidney microsome autoimmune hepatitis preceded by alopecia 3 years earlier. Both pathologies were greatly improved by immunosuppressive therapy. Alopecia is a newly reported extrahepatic manifestation of type 2 autoimmune hepatitis. Its appearance could alert the clinician to an increased risk of autoimmune hepatitis in children.

Infected teratoma of lower posterior mediastinum in a six-year-old boy.

A six-year old boy presented with prolonged unexplained fever caused by an infected teratoma of the lower posterior mediastinum. Modern imaging, combining ultrasonography with computed tomography, enabled the correct diagnosis of topography, extension and nature of this rare lesion to be made and explained the clinical features. Follow-up CT showed regression of the abscess after antibiotics thus permitting elective surgery.

Early diagnosis and treatment of neonatal medium-chain acyl-CoA dehydrogenase deficiency: report of two siblings.

Two siblings are reported who were symptomatic in the neonatal period. The first died suddenly at 4 days of age after regurgitating a meal. The postmortem examination showed steatosis of the liver, kidney and muscle. In the second, medium-chain acyl-CoA dehydrogenase (MCAD) deficiency was diagnosed at 3 days of age with muscular hypotonia, vomiting, hyperammonaemia and mild acidosis. Thus disorders of fatty acid oxidation should also be considered in newborns. The biochemical work up indicates that in neonates, analysis of serum medium-chain fatty acids and of acyl and free carnitine are more likely to lead to a diagnosis than determining dicarboxylic acids alone in urine. Long-term treatment was effective and monitored by the acyl/free carnitine ratio.

Bile acids and bile alcohols in two patients with Zellweger (cerebro-hepato-renal) syndrome.

The Zellweger cerebro-hepato-renal syndrome (CHRS) is a rare hereditary disease in which there is a generalized deficiency of peroxisomal function. Liver peroxisomes are important for the conversion of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid into cholic acid, and, consequently, 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid and metabolites of this bile acid precursor accumulate in serum and bile of patients with CHRS. Little is known about the urinary excretion of bile acids in this disease. Using gas chromatography-mass spectrometry we have analyzed serum bile acids and urinary excretion of bile acids and bile alcohols in two Swiss male CHRS patients. As expected, serum concentrations and urinary excretions of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid and 3 alpha,7 alpha,12 alpha,24-tetrahydroxy-5 beta-cholestanoic acid were elevated, which is probably an obligatory finding in CHRS. In addition, the urinary excretion of 1,3,7,12-tetrahydroxy-5 beta-cholanoic acid (a very polar unusual bile acid) was increased (99-1556 nmol/24 h). In contrast, the excretion of the major urinary bile alcohol, 27-nor-5 beta-cholestane-3 alpha, 7 alpha,12 alpha,24,25-pentol was found to be normal. 3 alpha, 7 alpha,12 alpha-Trihydroxy-5 beta-C29-dicarboxylic acid, a metabolite of 3 alpha,7 alpha,12 alpha-trihydroxy-5 beta-cholestanoic acid previously believed to be obligatory in CHRS, was found only in one of our patients.

Bile acid pattern in human amniotic fluid.

Individual bile acids were determined in twenty-nine amniotic fluid specimens obtained from twenty-six women between the 32nd and 41st week of gestation. Total bile acid concentration ranged from 0.4 to 4.8 mumol/l with a mean of 1.57 mumol/l. Besides the two major bile acids of man, cholic acid and chenodeoxycholic acid, 3beta-hydroxy-5-cholenoic acid was found in all, lithocholic acid in ten and deoxycholic acid in nine of the twenty-nine amniotic fluid samples. 3beta-Hydroxy-5-cholenoic acid averaged 39.8% of total bile acids during 32-37 weeks of gestation and 20.2% at term (P less than 0.01). These findings point towards important differences between fetal and adult bile metabolism and may reflect maturation of hepatic bile acid biosynthesis near term.

Bile acids in serum and bile of infants with cholestatic syndromes.

The concentration of individual bile acids in serum was measured in 18 neonates and infants with various cholestatic conditions (extrahepatic biliary atresia, neonatal hepatitis syndrome, chronic intrahepatic cholestasis and posthemolytic cholestasis). The cholate/chenodeoxycholate ratio in serum was smaller than one in all patients with neonatal hepatitis syndrome or extrahepatic biliary atresia, cholestatic conditions which were accompanied by signs of liver cell injury. It was greater than one in the patients with chronic intrahepatic cholestasis. Administration of cholestyramine to patients with patent extrahepatic bile ducts decreased the total concentration bile acids in serum and elevated the cholate/chenodeoxycholate ratio. Thus, cholestyramine administration may be of diagnostic value for evaluation of bile duct patency in cholestasis of infancy. Differences between the bile acid pattern in serum and bile were observed. Thus, the cholate/chenodeoxycholate ratio was always higher in bile than in serum. 3beta-hydroxy-5-cholenoic acid found in serum was not detectable in bile. This finding suggests that impairment of biliary excretion rather than increased hepatic synthesis is responsible for elevation of this monohydroxy bile acid in serum.

Determination of bile acid concentration in human amniotic fluid for prenatal diagnosis of intestinal obstruction.

Bile acid concentration was measured in amniotic fluid obtained for standard indications from 11 healthy pregnant women without polyhydramnios (28 to 42 weeks of gestation) and from 9 patients with polyhydramnios (28 to 38 weeks of gestation). Two of the latter women delivered infants with intestinal obstruction distal to the papilla of Vater, a condition that causes regurgitation of bile into the amniotic fluid. In the women without polyhydramios, the total bile acid concentration ranged from 1.4 to 2.4 micronmol/liter. In the seven patients with polyhydramnios not associated with fetal intestinal obstruction, the bile acid concentration in amniotic fluid was not significantly different (0.9 to 1.9 micronmol/liter). By contrast, the bile acid concentration in amniotic fluid specimens from the two patients with polyhydramnios who gave birth to children with intestinal obstruction was considerably elevated (30.3 to 83.1 micronmol/liter). These findings suggest that determination of bile acid concentration in amniotic fluid permits prenatal diagnosis of intestinal obstruction distal to the papilla of Vater.

[Detection of 3 beta-hydroxy-5-cholenoic acid in human amniotic fluid]. / Nachweis von 3beta-Hydroxy-5-cholensäure im menschlichen Fruchtwasser

Studies of the bile acids of human meconium suggest that a fetal pathway of bile acid synthesis exists which leads to formation of 3beta-hydroxy-5-cholenoic acid, a bile acid not found in serum of healthy pregnant women. To obtain additional support for this hypothesis, cholic, chenodeoxycholic, and 3beta-hydroxy-5-cholenoic acid were measured in amniotic fluid specimens from 18 pregnant women without liver disease. The finding of a considerable percentage of 3beta-hydroxy-5-cholenoic acid (mean: 34 molar %; range 3-71 molar % of total bile acids) in amniotic fluid strengthens the hypothesis that a fetal pathway of bile acid synthesis exists which begins with oxidation of the cholesterol side chain.

[Cow's milk protein intolerance in childhood. Review of 30 cases]. / L'intolérance aux protéines du lait de vache chez l'enfant

Retrospective clinical study of 30 cases of cow's milk protein intolerance with a long term follow-up (3-141/2 years) in 22 cases. The onset of the disease is usually in the first 6 months, following a short exposure to cow's milk proteins. A later onset is also possible, particularly following an intestinal infection which seems to favor the sensibilisation. Usually the digestive disturbances predominate and are often associated with respiratory, cutaneous and other general problems (especially unexplained prolonged fever). In about half the cases, laboratory studies reveal signs of exsudative enteropathy or generalized malabsorption with lesions of varying severity of the jejunal mucosa. Clinical observation and investigation allows us to divide the patients into three groups according to different manifestations: 1. acute anaphylactic, 2. chronic and benign (colitis), 3. chronic and severe, with accompanying malnutrition and intestinal malabsorption. This last category leads occasionally to diagnostic difficulties in distinguishing it from coeliac disease. Whatever manifestations encountered, the disease is usually transitory, and disappears between the age of 2 and 21/2 years, but can also persist for a much longer time. The long-term follow-up study showed complete catch-up growth, absence of further gastro-intestinal problems, and a low incidence of other allergic diseases (18%).