Alpha fetoprotein is increasing with age in ataxia-telangiectasia.

The elevated serum alpha fetoprotein (AFP) concentration in ataxia-telangiectasia (A-T) patients has been known for decades, but the individual variation of AFP levels over time has not been studied. We have followed 12 patients (five girls and seven boys) for 1-12 years (mean 5.5 years) measuring in each patient AFP 2-8 (mean 4) times. Serum AFP levels were increased in all patients, mean 168.7 (range 40-373) kU/L, and without significant differences between the patients. There was a significant age related difference in the serum AFP level. A positive linear relationship (r=0.61, p=0.04) could be found between AFP level and age. Albumin levels were within normal range and did not change with age. Four patients had slightly increased aspartate aminotransferase (AST) levels. None of the patients had serological evidence of infectious hepatitis, and none had increased levels of carcinoembryonic antigen. Repeated standardized observations of gait function revealed no major difference in neurological deterioration between our patients. All had classical A-T disease and mainly truncating mutations; 21 out of 24 possible mutations were either frameshift or nonsense. Four were homozygous for the Norwegian ATM founder mutation. No correlation between serum AFP levels and the different ATM genotypes could be found. We conclude that serum AFP is not only elevated, but also is continuously increasing with age in patients with classical A-T disease.

The impact of an early truncating founder ATM mutation on immunoglobulins, specific antibodies and lymphocyte populations in ataxia-telangiectasia patients and their parents.

Eleven Norwegian patients (aged 2-33 years, seven males and four females) with Ataxia-telangiectasia (A-T) and their parents were investigated. Five of the patients were homozygous for the same ATM mutation, 3245delATCinsTGAT, a Norwegian founder mutation. They had the lowest IgG2 levels; mean (95% confidence interval) 0.23 (0.05-0.41) g/l versus 0.91 (0.58-1.26) g/l in the other patients (P = 0.002). Among the 11 A-T patients, six had IgG2 deficiency, six had IgA deficiency (three in combination with IgG2 deficiency) and seven had low/undetectable IgE values. All patients had very low levels of antibodies to Streptococcus pneumoniae 0.9 (0.4-1.4) U/ml, while normal levels were found in their parents 11.1 (8.7-13.4) U/ml (P < 0.001). A positive linear relationship between pneumococcal antibodies and IgG2 (r = 0.85, P = 0.001) was found in the patients. Six of 11 had diphtheria antibodies and 7 of 11 tetanus antibodies after childhood vaccinations, while 4 of 7 Hemophilus influenzae type b (Hib) vaccinated patients had protective antibodies. Ten patients had low B cell (CD19+) counts, while six had low T cell (CD3+) counts. Of the T cell subpopulations, 11 had low CD4+ cell counts, six had reduced CD8+ cell counts, and four had an increased portion of double negative (CD3+/CD4-/CD8-) gamma delta T cells. Of the 22 parents (aged 23-64 years) 12 were heterozygous for the ATM founder mutation. Abnormalities in immunoglobulin levels and/or lymphocyte subpopulations were also observed in these carriers, with no correlation to a special ATM genotype.

Untreated meningococcemia in two siblings.

In September 1982 two siblings were admitted to hospital within a few days of each other, with almost identical symptoms of meningococcemia. One of them had been discharged from hospital four days previously, fully treated to meningococcal meningitis. Two systemic meningococcal isolates and nasopharyngeal meningococci from patient No 1 were B:15:P1. 16 strains as well as one nasopharyngeal isolate from patient No 2. One nasopharyngeal isolate from the father was a non-encapsulated 15:P1. 16 strain. The two systemic isolates were clearly different with respect to the class 5 outer membrane protein(s); the second closely resembled the various nasopharyngeal isolates, all of which were identical. Only the two patients mounted detectable bactericidal antibody activity as measured by using human complement. Convalescent serum from patient No 1 after the second episode was bactericidal against the first but not the second isolate. No differences among patients and parents were found by measuring opsonizing activity. The clinical picture and the laboratory results seem to indicate that both children, one after a treated meningitis episode, had benign meningococcemia which subsequently ran its course untreated and without complications.

Cystic duplication of the colon combined with nonrotation anomaly imitating pyloric stenosis.

Cystic duplication of the large intestine is a rare anomaly which may give no clinical symptoms. When combined with a nonrotation anomaly it may enhance the symptoms of a high gastro-intestinal obstruction. A case is presented where the combination of these two conditions gave intermittent symptoms simulating a duodenal or a pyloric stenosis.