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For the mentally retarded, bowel and bladder control are important prerequisites for an independent life. A study of these functions was made in a cohort of children born in Northern Finland in 1966. Relevant data up to the age of 20 years were obtained for 105 of the 132 children with mental retardation (IQ less than 70) who were alive at that age. 80 per cent had attained bowel control at a mean age of 4.2 years, but 30.5 per cent were still encopretic at seven years, and 19 per cent at the age of 20 years. Full bladder control had been achieved by 62.9 per cent at the age of seven and by 82.9 per cent at the age of 20. It is concluded that systematic, appropriate toilet training could improve these figures markedly.

We describe 11 infants with congenital lactase deficiency, whose age at diagnosis varied from 6 to 88 days. At the time of admission, 7 of 10 infants had hypercalcemia. Five of the seven infants for whom renal ultrasonography was performed at the time of diagnosis had medullary nephrocalcinosis. Hypercalcemia ceased within a week of the start of a lactose-free diet. At the time of reevaluation, at the ages of 2 to 10 years, one of the patients still had hypercalciuria and nephrocalcinosis was still present in 3 of 11 patients. The mechanism of hypercalcemia is unclear but may be related to metabolic acidosis or may be promoted by the lactose effect (i.e., by nonhydrolyzed lactose that has a direct enhancing effect on calcium absorption in the ileum).

The occurrence of a nephroblastoma in a 2-year-old girl with Mulibrey nanism is reported. As this tumor has also been reported in some other "mesodermal dysgenesis" syndromes, it seems probable that patients with this form of congenital disease run an abnormally high risk of Wilms' tumor.

Penttinen, R., Sipola, E., Kouvalainen, K., Simila, S. and Remes, M. (Department of Medical Chemistry, University of Turku, and Department of Paediatrics, University of Oulu, Finland). Arthropathic osteogenesis imperfecta. Acta Paediatr Scand, 69:263, 1980.—A 14-year-old girl gradually developed severe osteoporosis and destructive generalized joint disease, resulting in joint stiffness and anchyloses. She also had moderate hydroxyprolinemia and hydroxyprolinuria. Rheumatoid arthritis was highly unlikely. Anamnestic data revealed two long bone fractures. Collagen biosynthesis was studied in fibroblasts cultured from the patient's skin. Chromatograms of 3H-labelled culture media proteins on ion exchange celluloses revealed an increased ratio of type III collagen to type I collagen when compared with the chromatograms of age-matched control fibroblasts. This finding is typical of certain cell strains in osteogenesis imperfecta. The patient might thus express a new variety of osteogenesis imperfecta with chronic arthropathy.

Pi phenotypes were classified by isoelectric focusing of the sera of 200 full-term Finnish newborns at the age of 3--5 days. The phenotype PiM was found in 95% of the neonates. The frequencies of the alleles PiM1, PiM2 and PiM3 were 0.682, 0.189 and 0.129, respectively. The serum concentration (mean +/- SD) of alpha-1-antitrypsin (alpha 1-AT) in the whole study group was 2.72 +/- 0.61 g/l. The concentration of alpha 1-AT in the newborns with the phenotype PiM3 (1.79 +/- 0.65 g/l) was significantly lower (p less than 0.025) than in other PiM subtypes. No difference in serum concentrations of alpha 1-AT between boys (2.78 +/- 0.66 g/l) and girls (2.66 +/- 0.55 g/l) was observed.

Sjögren's syndrome (SS) in its classical form, which includes keratoconjunctivitis sicca, xerostomia and recurrent enlargement of the salivary glands, is associated with a connective tissue disease in at least half the patients. According to the present study of three patients with SS, achalasia and gastric hyposecretion seem to be either further manifestations of SS, or separate phenomena associated with SS. The gastric hyposecretion involves both the hydrochloric acid and the total volume of the secretion, but the gastric mucosa has a normal appearance on microscopy. Because of the simultaneous presence of achalasia, gastric hyposecretion and reduced salivation, we have called the combination "achalasia sicca". The reduction in the secretions of the upper gastrointestinal tract might have a pathogenic association with achalasia.

Gastric acid secretion in nineteen children with celiac disease remained almost unchanged and the level of fasting serum gastrin was comparable with that of a control group of the same age. The absorption of vitamin B12 was significantly decreased, most clearly in the infants with celiac disease as compared with their controls. The serum B12 level, however, was decreased only in the oldest children. The results suggest that the mucosal lesion in the small intestine is most extensive in the youngest children, but the absorption defect of vitamin B12 becomes clinically significant only after a long duration of the disease and not in childhood.

The absorption of paracetamol from syrup, tablet and two different suppository bases was compared in six adult volunteers using urinary excretion measurements. The total amount of paracetamol and its metabolites excreted and the peak excretion rates were lower from the suppository bases than from the oral dosage forms. Absorption was a little better from a polyethylene glycol suppository base than from a triglyceride base. The antipyretic efficacy of a paracetamol syrup and suppository at a dose of 10 mg/kg was compared in 30 children between the age of 4 months and 12 years, who had infections and a rectal temperature above 38.5 degrees C. Both dosage forms produced a significant decrease in temperature, the greatest fall being about 2 hours earlier with the oral dosage form. The syrup also seemed to be significantly (p less than 0.05) more effective (maximum fall of temperature 1.58 degrees C) in reducing fever than the suppository, which produced its greatest fall of temperature (1.24 degrees C) six hours after insertion of the suppository. From the practical point of view both forms can be regarded as safe and effective antipyretics.

Serum levels of 5 immunoglobulins (IgG, IgA, IgM, IgD and IgE) were determined at frequent intervals in the course of bacterial meningitis in children. 59 patients were examined; 27 with Haemophilus influenzae meningitis, 23 with meningococcal and 9 with pneumococcal meningitis. All 5 immunoglobulins increased during the 2-week course of bacterial meningitis. IgM was the immunoglobulin class responding most rapidly, regularly and intensively. IgG increased moderately. However, practically no rise of the IgG level was observed in children with H. influenzae meningitis. The elevation of the IgA and IgE levels possibly suggests that meningitis may also cause synthesis of IgA and IgE antibodies. The results of the study indicate that antibodies of all the 5 immunoglobulin classes are probably involved in the defense against the causative microbes in bacterial meningitis.

Concentrations of two primary bile acids (cholic and chenodeoxycholic acids) were determined by radioimmunoassay in the serum of infants and children at ages ranging from 1 hour to 15 years. The same bile acids were also measured in umbilical cord serum. Concentrations of the primary bile acids were significantly higher in the serum of 1-hour old infants than those in the umbilical cord serum or the peripheral vein serum of adults. The levels of cholic and chenodeoxycholic acid remained high until the age of 6 months, being about 5-fold higher than those in the sera of adults. Primary bile acid concentrations reached the adult level by the age of 1-2 years. These results indicate that developmental changes occur in the metabolism and excretion of bile acids in man. The relatively high concentrations of the primary bile acids in serum during the first 6 months of life suggest that up to this age, the mature ability of the liver to excrete the bile salts into the bile and/or to clear them from the circulation has not yet been reached.

Twenty-nine cases of severe type 7 adenovirus pneumonia in children ages 8 months to 6 4/12 years were observed in northern Finland in 1967 and 1968. Adenovirus type 7 was isolated from 17 patients. The other 12 had serologic evidence of adenovirus infection. The clinical picture and complications were compared with those of 17 children with pneumonia associated with bacterial or other viral infections hospitalized during the same period. The clinical course of the adenovirus type 7 infection was especially severe. Extrapulmonary manifestations (meningism, encephalitis, hepatomegaly, heart failure, and hemorrhagic tendency) were common especially in children less than 3 years of age. Three of the 29 patients died, and 4 of the survivors (14 per cent) had permanent pulmonary damage: 2 had bronchiectasis and 2 had residual lung fibrosis.

A newborn boy is presented with proteinuria, edema, aplasia of patellae, and extension defect in the elbows. Seven of his relatives have, or have had, nephropathy and skeletal deformities and two of them have only skeletal deformities. Spontaneous recovery of proteinuria and edema occurred at 2 weeks of age. The family history, clinical signs, and rapid improvement in the patient's condition confirmed the diagnosis of hereditary onycho-osteodysplasia (HOOD) with neonatal nephrosis-like disease. Other causes of the neonatal nephrotic syndrome, such as congenital nephrosis, congenital syphilis, and renal vein thrombosis could be excluded. The patient described remained symptomless, with the exception of skeletal deformities until the age of 24 months. The incidence and prognosis of nephropathy in HOOD is discussed on the basis of the reported family and data from the literature.

Thirteen breast-fed one-month-old infants with prolonged jaundice not due to known causes were included in this study. All infants were investigated at one and twelve months of age. Serum concentrations of total (TB) and conjugated bilirubin (CB), aspartate (ASAT) and alanine aminotransferase (ALAT), alkaline phosphatase (AP), alpha-1-antitrypsin (alpha-1-AT), alpha-1-fetoprotein (AFP) and the two primary bile acids; cholic (CA) and chenodeoxycholic acid (CDCA) were determined at both ages. The Pi-phenotype of alpha-1-AT was determined at the age of twelve months. The serum concentrations of TB, CB, AP and AFP were elevated at the age of one month but were normal at the age of twelve months. No changes in the serum concentrations of ASAT or ALAT were observed between one and twelve months of age, and the values were within the reference ranges. The serum concentrations of alpha-1-AT were within the reference range at both ages. Two infants were heterozygous for MZ, and they had normal serum alpha-1-AT concentrations. The serum concentrations of CA and CDCA were elevated at the age of one month and were still significantly elevated at the age of twelve months indicating that the infants had slight cholestasis at the age of one month, and that the cholestasis had largely subsided by the end of the first year of life.

Hyperglycinemia was induced by dipropylacetate (DPA) (dose 14-41 mg/kg per day) in 10 Finnish epileptic patients with neurologically disabling diseases of various kinds. When comparing the levels of glycine in plasma, cerebrospinal fluid and urine from the patients with 10 otherwise comparable patients, and normal values there was a fourfold excretion of glycine in urine. All the treated patients had elevated CSF (49 +/- 23 mumol/l) and plasma (475 +/- 76 mumol/l) glycine concentrations. The plasma/CSF glycine ratio was not influenced by the treatment. In comparison with corresponding values in nonketotic hyperglycinemia and ketotic hyperglycinemia, this condition probably arises in a manner similar to secondary hyperglycinemia in organic aciduria. DPA probably influences metabolism in a way similar to some metabolites of amino acids in organic acidurias.

The capacity of ibuprofen to reduce fever in children was compared with that of aspirin, paracetamol, aminophenazone and indomethacin. The series of cases studied consisted of 79 patients in the age range 3 months to 13 years and with a rectal temperature above 38.5 degrees C. Temperatures were recorded at 15 and 30 minutes, and 1,2,4 and 6 hours after challenge with the drug. The antipyretic effect of ibuprofen with a dose of 6 mg/kg was optimal and twice that of aspirin or paracetamol and similar to that of aminophenazone. The antipyretic effect of indomethacin was about 12 times that of ibuprofen. This ratio is almost the same as what is said to occur between the antirheumatic effects between these drugs. Ibuprofen with a dose of 6 mg/kg would thus appear to be a useful antipyretic drug when both antipyretic and antirheumatic effects are needed.

A sternal abscess appeared 14 months after BCG revaccination of a 14-year-old girl. Culture taken from the abscess was positive for Mycobacterium bovis, which was identified as a BCG strain.

Summary The effect of prenatal dexamethasone therapy (12, 8 and 4 mg doses given intramuscularly on three consecutive days) on ACTH levels in maternal plasma (n = 33), mixed umbilical cord plasma (n = 31) and plasma from the newborn (n = 29) was studied, and the results were compared with those obtained in 56 healthy parturients and 50 of their newborn. Maternal ACTH after delivery was significantly lower in the mothers treated with dexamethasone than in the control group. Cord ACTH values were similar in the two groups. ACTH levels fell during the early neonatal period, but only at 12 to 24 hours were the ACTH levels significantly lower in the dexamethasone group than in the controls. Gestational age, birth weight and the interval between the dexamethasone therapy and delivery had no significant effect on cord ACTH levels. Short-term prenatal dexamethasone therapy seemed to have very little effect on ACTH secretion in the mother, in the fetus and in the newborn.

The plasma concentration of ACTH (by radioimmunoassay) was measured in 56 healthy parturients and their newborns. Umbilical cord and maternal venous blood were collected immediately after delivery. In addition one venous blood sample was taken from 50 newborns at the age of 15, 30, 60 min, 2, 6, 12, or 24 h. The maternal and cord plasma ACTH levels were higher than the levels in healthy nonpregnant women. There are no differences between the mean maternal (226 +/- 146 pg/ml) and cord (226 +/- 147 pg/ml) values of ACTH. The high ACTH levels of cord plasma remain unchanged for 30 min, decrease significantly during the 1-6 h after birth, because of the elimination process of the circulated foetal ACTH, and increase over the next 12-24 h and slightly thereafter indicating an initiation of neonatal pituitary ACTH secretion. The plasma ACTH level in the mothers with membranes ruptured for 1-5 h was significantly (P less than 0.05) higher compared with that in the mothers with membranes ruptured for less than 1 h. However, the duration of ruptured membranes appeared to have no effect on the cord blood ACTH level.

Heterozygotes for nonketotic hyperglycinemia (NKH), a disorder of glycine degradation, have a slightly abnormal metabolism of glycine. As the severe neurological symptoms which are characteristic for the homozygotes are at least partially due to a disturbance of glycine function as a neurotransmitter, minor neuronal dysfunctions might be expected also in heterozygotes. Although their general health was within normal limits in these 13 heterozygotes, slight neurological symptoms and signs were observed. Neurophysiological investigations revealed disturbance of the vestibular function in six subjects, preponderance of beta-wave activity in five, subnormal amplitude of a-wave, and shortening of implicit time of the first oscillatory potential (OPI) in the retinography. Functioning of peripheral nerves appeared normal in measurements of motor conduction velocity, distal latency and amplitude of muscle response. These minor dysfunctions of the central nervous system may well be due to a slightly abnormal degradation of glycine in heterozygotes for nonketotic hyperglycinemia.

In this study peripheral blood smears from 29 patients (17 males and 12 females; mean age 28 years, range 3-65 years) with a confirmed diagnosis of the Finnish type of sialic acid storage disease (FSASD) and 200 controls with mental retardation without any evidence of metabolic disease were examined for the presence of vacuolated lymphocytes. Urine samples were analysed by thin-layer chromatography for free sialic acid. Only 62% of the patients with FSASD had a clearly increased percentage of vacuolated lymphocytes (greater than normal mean + 2 s.d.). In thin-layer chromatography all the FSASD patients gave a positive test result. No false positive or negative results were obtained. Electronmicroscopical examination of peripheral blood lymphocytes demonstrated only non-specific changes in a few cells. Examination of peripheral lymphocytes for vacuoles is not a reliable screening test for FSASD. The screening method of choice is the analysis of free sialic acid by thin-layer chromatography.

Eight infants with cow's milk intolerance (CMI) were studied for basal and maximal gastric acid secretion and the fasting serum gastrin level. All these patients had clinical malabsorption. Jejunal biopsies revealed subtotal villous atrophy in six children and slight changes in the remaining two. The mean maximal acid secretion in the infants with CMI was significantly decreased being 85 +/- 78 mumol/h/kg (mean +/- SD), as compared with a control group of the same age with a corresponding value of 233 +/- 66 mumol/h/kg. The fasting serum gastrin level was elevated, being 104 +/- 116 pmol/l in the study group and 37 +/- 10 in the controls. Three infants with CMI underwent gastric biopsy. Marked changes with epithelial degeneration and prominent cellularity in the lamina propria were seen in two patients. The injury was most severe in the antrum of the stomach. When these patients with CMI were treated with human or soy milk, the maximal acid secretion returned normal in six months.

Nonketotic hyperglycinemia (NKH) is a rare disorder of glycine degradation with autosomal recessive inheritance. 1 There are about 120 cases reported in the literature, 2 and most of them represent a neonatal type of NKH. The defect in the glycine cleavage reaction, which has been demonstrated in both liver 3 and brain 4 tissue of the patients, leads to an accumulation of glycine. This is accompanied by the rapid development of severe neurologic symptoms. If not lethal in the neonatal period, NKH leads to severe psychomotor retardation. The pathogenesis of the neurologic symptoms is not well understood, but the failure of the therapeutic experiments 5,6 and the observation of a delay in the process of myelination in neonates dying of NKH 7 suggest that an abnormal metabolism of glycine also exists in the fetus with NKH. To study this particular aspect, we performed consecutive recordings of EEGs and determinations of

Two brothers with typical clinical findings of the COFS-sundrome are described. In the cranial CT performed on the younger patient at the age of 2 years and 6 months, foci of intracranial calcification located symmetrically in the region of the lenticular nucleus and hemispheric white matter were noted. This finding is clearly distinguishable from the other known patterns of intracranial calcification and could be pathognomonic of the COFS-syndrome.

In Finland, 19 children, born 1964--1977, from 13 families, have been diagnosed as suffering from nonketotic hyperglycinemia (NKH). This gives an incidence for NKH in the Finnish population of 1:55,000 newborns. The majority of these children were born in the northern part of the country, where the incidence is 1:12,000. The geographical distribution of the birth-places of the grandparents also seems to point towards an enrichment of the gene in northern Finland. An autosomal recessive mode of inheritance for this disease seems probable, since the corrected proportion of affected siblings (Apert's a priori method) is 0.288. Abnormally high plasma glycine concentration and elevated glycine urinary excretion in the parents of the NKH-children suggest the existence of a minor metabolic defect in heterozygotes of this disease. Some of the healthy siblings of the NKH-patients also show similary elevated levels. However, a definite diagnosis of the NKH-heterozygote state cannot easily be made on the basis of these laboratory findings, as the levels in some individuals are very close to, or even overlap corresponding values in a normal material.

A previously healthy 2 1/2-year-old boy from a healthy family developed agammaglobulinemia with arthritis 3 months after infectious mononucleosis (IM). The response of serum immunoglobulins at the initial stage of IM was typical, with greatly elevated IgM and a positive IM-specific heterophil antibody test. A secondary celiac disease was diagnosed one year after IM. Considering the serum immunoglobulin levels and the normal half-lives of IgM and IgG, it seems very probable that the synthesis of immunoglobulins ceased about one month after the onset of IM. The role of suppresor T-cells in the development of acquired secondary agammaglobulinemia is discussed.

The capacity of benorylate, an ester of acetylsalicylic acid and paracetamol, to reduce fever in children was compared with that of the components as such or as a combination. The series of cases studied consisted of 66 patients between the ages of 4 months and 12 years with rectal temperatures above 38.5 degrees C. Temperatures were recorded at 15 and 20 min and 1, 2, 4 and 6 hrs after the administration of the drug. The antipyretic effect of combined acetylsalicylic acid (11 mg/kg) and paracetamol (14 mg/kg) was superior to the effect of benorylate with a dose of 25 mg/kg and even of 50 mg/kg as well as better than the effect of either drug alone. Acetylsalicylic acid (10 mg/kg) and paracetamol (12.5 mg/kg) alone produced a significantly greater antipyretic effect than benorylate with a dose of 25 mg/kg. Given in a dose of 35--40 mg/kg, benorylate seems to have a significant antipyretic effect. However, this effect is clearly smaller than that of either of its components, acetylsalicylic acid or paracetamol. Therefore benorylate is probably not suitable to be used as a general antipyretic agent in children.

Three Finnish infants with a severe neonatal-onset-type of nonketotic hyperglycinemia were treated with strychnine nitrate in a daily dosage of 0.2 to 0.9 mg/kg, given orally in four doses. In order to lower the plasma and CSF-glycine concentrations concomitant exchange transfusions (200 to 300 ml/kg of heparinized blood) were carried out in two of these infants. Although the strychnine therapy was started at ages 15, 40, and 62 hours, the strychnine produced no clinical effect, and the exchange transfusion caused only a transient decrease in the plasma glycine level. Despite treatment, the clinical course was the same as in the majority of children with the severe form of the disease—all died within the first ten days of life. Impressive effects of strychnine treatment initiated in two infants at ages 5 and 6½ months, and given in addition to sodium benzoate and anticonvulsants, have been reported. These cases, however, probably represent a less severe type of nonketotic hyperglycinemia. Nevertheless, the therapeutic failure in the present cases probably indicates that strychnine treatment does not solve the therapeutic problems of severe forms of NKH.

Dermatological changes are rare in childhood coeliac disease. A 12-year-old girl is described with untreated coeliac disease and chronic cutaneous vasculitis. The skin lesions cleared completely and growth was restored after treatment with a gluten-free diet.

Serum levels of immunoglobulins (IgG, IgA, IgM, IgD and IgE) were determined at frequent intervals in the course of anaphylactoid purpura (AP) in children. AP was cured without complications in 16 out of 26 cases, recurring in 7 cases. Melena was manifested in 9 cases and nephropathy in 5. The levels of IgA and IgM were elevated in AP, but serum IgG, IgD and IgE showed no significant changes. The serum level of IgM was significantly (p less than 0.0125) higher in patients with AP nephropathy than in those with recent AP. The elevated serum IgA and IgM levels are possibly related to the pathogenesis of AP and/or its renal involvement.

The concentrations of the two secondary bile acids (deoxycholic (DCA) and sulpholithocholic (SLCA) acid) were determined by radioimmunoassays in the serum of infants and children at ages ranging from 1 hour to 15 years. The same bile acids were measured also in the umbilical cord serum. The concentrations of the secondary bile acids in the serum of 1-hour old infants corresponded to those in the umbilical cord serum. Secondary bile acid serum concentrations were after the age of 7 days and up to the age of 3 to 6 months significantly lower than those in the umbilical cord serum. After the age of 6 months a significant increase in DCA serum concentrations could be shown. During the first 6 months of life DCA concentrations were clearly lower than those of SLCA. Our observations suggest that in the perinatal period DCA is mainly of maternal origin and that an alternate hepatic pathway may exist for the synthesis of lithocholic acid in early infancy.

36 children aged 0.13 to 13.05 years with severe manifestations of atopy were studied for circulating parietal cell antibodies (PCA), fasting serum gastrin and ferritin. Gastric acid secretion was measured using a pentagastrin test. In addition, 21 gastric and 28 jejunal biopsies were taken for evaluation of the mucosal morphology. In infants the gastric secretion studies were repeated after a three month hypoallergic diet.

Mortality among children with mental retardation (IQ less than 71) and mental subnormality (IQ: 71-85) up to the age of 17 years was studied in the 1966 one-year birth cohort of Northern Finland. The 12,058 liveborn children included 97 children, 8.0 per thousand, with severe mental retardation (IQ less than 50) and 68 children or 5.6 per thousand with mild mental retardation (IQ: 50-70). In addition, there were 162 children or 13.4 per thousand who were mentally subnormal (IQ: 71-85). The death rate among the children with mental retardation was 158 per thousand as compared to 22.6 per thousand among children with normal intelligence and was significantly higher among the mentally retarded of all ages. This is mainly an effect of the very high mortality in children with severe mental retardation, predominantly cases of Down's syndrome. It is concluded that mental retardation per se is not necessarily associated with an increased death rate, but the underlying etiology or additional complicating disorders may predispose the child to infections in particular, these being the leading cause of death among the mentally retarded children studied here.

The clinical features, the results of gastric secretory function tests, and the duodenojejunal morphology of six infants (aged 0.42–1.23 years) with anemia and melena considered to be due to latent cow's milk intolerance (LCMI) were compared with the findings in nine infants (aged 0.19–0.87 years) with cow's milk-induced malabsorption (CMI). The infants with LCMI had a short period of breast feeding, normal weight gain without symptoms of malabsorption, and no atopic history. The maximal acid secretion was decreased (P

Non-ketotic hyperglycinaemia (NKH) is a rare disorder of amino acid metabolism, causing severe, frequently lethal neurological symptoms in the neonatal period. There is no curative therapy, and attempts at prenatal diagnosis have been unsuccessful. In the present study the usefulness of the determination of the glycine/serine ratio in the prenatal diagnosis of NKH was studied. The glycine/serine ratio of the amniotic fluid of the last trimester of pregnancies with a fetus affected with NKH was higher (8.5 +/- 3.3; mean +/- SD) than in pregnancies of NKH-heterozygote mothers with a healthy fetus (4.1 +/- 1.7) or than in pregnancies of healthy mothers (4.3 +/- 1.5). There is, however, overlapping of individual values, which limits the usefulness of this test for prenatal diagnosis of NKH.

The antipyretic activity of three N-aryl-anthranilic acid derivatives, mefenamic acid, tolfenamic acid and flufenamic acid, was compared and their optimal antipyretic dose determined in a trial in 87 children (aged 5 months to 15 years), who suffered from infections and fever exceeding 38.5 degrees C. Tolfenamic acid proved to be the most potent antipyretic agent of the three drugs; it was eight times more powerful than mefenamic acid and three times more powerful than flufenamic acid. The optimal antipyretic doses were: mefenamic acid 4 mg/kg, tolfenamic acid 0.5 mg/kg and flufenamic acid 1.5 mg/kg. It is evident that the antipyretic activity of these anthranilic acid derivatives is even greater than their antirheumatic effect, the difference being most noticeable in the case of tolfenamic acid.

This report documents a rare occurrence of Sjögren's syndrome and achalasia of the cardia in two siblings (Table I). Sjögren's syndrome manifested itself at the ages of 4 and 8 years, and achalasia of the cardia at the age of 10 years in both girls. The familial occurrence of both these conditions is reviewed, and the genetic factors in their pathogenesis are discussed.

Autosomal dominantly inherited cataract was detected in 20 out of 36 members of a kindred. Three members with cataract and three without cataract also had renal hyperglycinuria. The coincidence, although probably fortuitous, may call for measurements of renal clearance of glycine in cases with inherited cataract.

Two males with the karyotype 46,XX are reported. In both individuals, the karyotype was determined in over 400 cells from lymphocyte, skin, and testis cultures.

The results of studies in which intravenous ornithine or proline loadings were administered to normal subjects suggest a rate-limiting function of ornithine-ketoacid aminotransferase in the conversion of ornithine to glutamate, and of proline oxidase in the conversion of proline to glutamate. The failure of Δ 1 -pyrroline-5-carboxylic acid to appear in the plasma and urine during ornithine-proline loading indicates the high capacity of Δ 1 -pyrroline-5-carboxylic acid dehydrogenase in the conversion of its substrate to glutamate. In two patients with hyperprolinaemia type II, the urinary excretion of Δ 1 -pyrroline-5-carboxylic acid increased slightly during ornithine loading. This suggests that this inborn metabolic disease exhibits a defect in the conversion of Δ 1 -pyrroline-5-carboxylic acid to glutamate and that ornithine may be converted to this substance.

A prepubertal girl with pure gonadal dys genesis and 46, XY karyotype is reported. Ex ploratory laparotomy was performed and bilateral gonadal streaks and a small left gonadal tumor were found at the place of the ovaries. The pathologic examination of this tumor revealed gonadoblastoma. The indication to laparotomy in patients with pure gonadal dysgenesis and 46, XY karyotype is discussed.

By the end of 1981 a total of 28 infants suffering from non-ketotic hyperglycinaemia had been diagnosed in Finland. The mean incidence in Finland is 1:55 000 newborns. All these infants represent the neonatal type, characterized by onset of rapidly progressing neurological symptoms during the first days of life. Attempted therapy, including strychnine, did not alter the clinical course, which in the majority of cases led to the death of the infants within the first weeks of life. Although the clinical condition appears to be normal at birth in these infants, the EEG is already pathological, and the CSF glycine level is as high as in fully developed NKH. Consequently, there is most probably prenatal brain damage in the neonatal type of NKH. The heterozygotes for NKH differ from healthy controls by significantly higher levels of plasma and urinary glycine, but a considerable overlap of individual values reduces the usefulness of this finding for active heterozygote diagnosis.