Catel-Manzke syndrome is characterized by Pierre Robin sequence and a unique form of bilateral hyperphalangy causing a clinodactyly of the index finger. We describe the identification of homozygous and compound heterozygous mutations in TGDS in seven unrelated individuals with typical Catel-Manzke syndrome by exome sequencing. Six different TGDS mutations were detected: c.892A>G (p.Asn298Asp), c.270_271del (p.Lys91Asnfs(∗)22), c.298G>T (p.Ala100Ser), c.294T>G (p.Phe98Leu), c.269A>G (p.Glu90Gly), and c.700T>C (p.Tyr234His), all predicted to be disease causing. By using haplotype reconstruction we showed that the mutation c.298G>T is probably a founder mutation. Due to the spectrum of the amino acid changes, we suggest that loss of function in TGDS is the underlying mechanism of Catel-Manzke syndrome. TGDS (dTDP-D-glucose 4,6-dehydrogenase) is a conserved protein belonging to the SDR family and probably plays a role in nucleotide sugar metabolism.

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Lung volumes and flows differ significantly between girls and boys calling for separate reference values for female and male subjects of the same age.

Urinary Hypoxanthine, Xanthine and Uric Acid Excretion in Newborn Infants with Perinatal Complications. Acta Paediatr Scand, 66: 713, 1977.-The concentration of hypoxanthine, xanthine and uric acid in the first 24-h urine of 105 newborn infants was measured densitometrically by thin-layer chromatography. 45 of them had moderate or severe perinatal complications. Among these newborns, 26 infants with perinatal complications (58 %) and 4 infants without perinatal complications (7 %) had an elevated urinary excretion rate of hypoxanthine. Urinary xanthine was not increased, uric acid was slightly higher in the group of infants with perinatal complications. It seems that a crucial mark is involved, if the rate of hypoxanthine exceeds 15% of the total urinary oxypurine excretion, or, if related to urinary creatinine, more than 0.075 pmol hypoxanthine/pmol creatinine. Apparently, with hypoxic newborns increased values of urinary hypoxanthine excretion can be used to quantify the lack of oxygen retrospectively.

Serum creatinine, uric acid, and hypoxanthine and xanthine concentrations were determined in 17 mother-infant pairs at the time of delivery. Creatinine and uric acid levels were nearly similar, but hypoxanthine and xanthine were more than twice as high in the blood of the infants than in the blood of their mothers. In the same newborns the urinary excretion of creatinine, uric acid, hypoxanthine and xanthine, uracil, cAMP, and cGMP was measured on the first and fourth day of life. Creatinine, uracil, and cAMP increased, hypoxanthine and xanthine, and cGMP decreased, whereas the output of uric acid was nearly the same on both days. Correlations of the excreted substances to each other were calculated.

Cardiazol induced seizures in rabbits showed that the highest oxypurine concentrations can be detected in the CSF 1 hour after the convulsions. There is a sharp decline continuing until the third hour. After that the CSF values remain nearly constant until the 24th hour being about ten times higher than in the controls. There is a good correlation of these results obtained through the densitometric thin-layer, enzymatic-oxymetric, and HPLC-methods. Creatinine and potassium were raised only during the first two hours postconvulsively. Uracil appeared in the CSF slightly higher at the 1 hour and at the 12 and 24 hour values. A parallel increase of the oxypurine and creatinine concentrations was found in the serum between 30 to 120 minutes postconvulsively. After that the raised serum values decreased slowly to the initial values. CSF samples were examined in 31 children postconvulsively: Hypoxanthine was found to be raised in 8 of 12 patients with severe grand mal seizures, 1 of 6 patients with hypsarrhythmia, 1 of 8 patients with short seizures (less than 2 min) and in all 5 patients with petit mal status. In contrast to these groups the hypoxanthine concentrations was raised only in 2 of 20 children with aseptic meningitis. The difference between the group of children with convulsions and the group of children with aseptic meningitis is significant (p less than 0.005). Also, the frequency of raised uric acid concentration is higher in the group of children with convulsions (70%) than in the group of children with aseptic meningitis (40%); (p less than 0.05).

Oxypurine analysis was done in the CSF of 190 children with different diseases. The patients could be divided into four groups: Group A, serving as controls, consisted of 56 children suffering from diseases without neurological signs, for example, leukaemia. 16% of them had raised hypoxanthine values greater than 7.5 mumol/l and 32% raised uric acid values greater than 12.0 mumol/l. Group B comprised 97 children suffering from diseases with neurological signs, for example, meningitis. For these patients the frequency of raised hypoxanthine and uric acid values in the CSF was twice as high as in Group A. Group C comprised 31 patients with different forms of cerebral convulsions. Among these patients 52% had raised hypoxanthine and 70% raised uric acid values. The findings of these patients are described in a previous paper (Manzke et al. 1981). Group D comprises 6 patients from whom CSF samples were taken postmortally. All these deceased patients showed extremely high hypoxanthine + xanthine and uric acid concentrations in their CSF.

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