Galactonic Acid in galactosemia: identification in the urine.

Galactose is converted to galactonic acid in vivo in man. Galactonate was isolated from the urine of galactosemia patients who had been given galactose orally. The identity of the galactonate was established by gas-liquid chromatography and by the preparation of derivatives.

Comparison of mental development in individuals with mosaic and trisomy 21 Down's syndrome.

During the past 15 years about 350 children with Down's syndrome have been seen at Children's Hospital of Los Angeles for psychological evaluation along with medical visits and other laboratory tests. Among this group there were 25 mosaic Down's syndrome children identified by chromosome analyses. They were matched for sex and chronological age with 25 trisomy 21 subjects and compared on psychological tests. The mosaic group demonstrated significantly higher intellectual potential, better verbal facility, and less visual perceptual difficulties than the trisomy 21 group. Their behavioral adjustment and personality characterisitcs were similar to those observed in other types of Down's syndrome. Since present psychological assessment techniques do not permit reaching valid conclusions about the ultimate intellectual status in very young infants with Down's syndrome, physicians and other professionals need to be careful when recommending early placement outside the home based merely upon the diagnosis.

Verbal dyspraxia in treated galactosemia.

Galactosemia is an inborn error of metabolism that causes life-threatening illness a few days after galactose-containing milk is fed to a newborn. Early treatment with a strict lactose-free diet results in rapid improvement, and, until recently, it was thought that the long-term prognosis in such infants was usually good. The speech characteristics of 24 patients treated for galactosemia were examined. Fifty-four percent had the specific speech disorder, verbal dyspraxia. This finding was not related to age at diagnosis, severity of symptoms in the newborn period, or to biochemical control. There may be, however, a relation between dyspraxia and diminished IQ scores observed in the group of patients with dyspraxia judged as "severe." The findings indicate the association of a specific and unusual speech defect with a specific and rare metabolic disorder.

Results of a survey of carrier women for the galactosemia gene.

A survey of 108 heterozygote women for the classic galactosemia gene, GALT, did not reveal that the carrier state was associated with premature ovarian failure or ovarian cancer. This survey did not support previous epidemiologic studies suggesting an increased risk for ovarian dysfunction in women with deficiency of the GALT enzyme.

Radiochemical assay of minute quantities of galactose-1-phosphate uridyltransferase activity in erythrocytes and leukocytes of galactosemia patients.

A sensitive radioisotopic method has been developed which can detect galactose-1-phosphate uridyltransferase (GALT) activity as low as 0.1% of normal control values in both erythrocytes and leukocytes. This assay utilizes carbon-14 labeled galactose-1-phosphate with high specific activity and requires removal of endogenous galactose-1-phosphate (Gal-1-P) and uridine diphosphate glucose (UDPGlc) through dialysis. Optimal exogenous UDPGlc concentration has been determined with a fixed concentration of Gal-1-P in the incubation. The rate of product, uridine diphosphate galactose (UDPGal), formation is monitored at three different times. Among 423 patients with galactosemia studied by this method, 363 patients exhibited no detectable GALT activity in their erythrocytes and 60 patients were found to have detectable erythrocyte GALT activity ranging from 0.02 to 5.0 units normal values: > 20 units). The former group of patients was designated as classic galactosemia (GG) and the latter group as galactosemia variant (GV). Leucocytes from ten patients belonging to the GG group also showed complete absence of GALT activity while leukocytes from two patients belonging to the GV group showed GALT activity at levels comparable with those found in their erythrocytes. Because there is extensive biochemical heterogeneity among galactosemia patients, we recommend that an assay with increase sensitivity be carried out on blood samples from galactosemia patients so that clinical, biochemical and molecular correlations made by different groups of investigators can be compared.

Prenatal diagnosis of galactosemia.

Prenatal diagnosis of disorders of galactose metabolism was done in one instance in a family with a known galactokinase deficiency and in six cases in five families at risk for galactosemia. The galactokinase activity in cultured amniotic cells was found to be normal, and the diagnosis was confirmed postnatally. In the six pregnancies at risk for galactosemia, four were considered to be unaffected and two to be affected. Of the latter, one was carried to term, and the erythrocyte transferase activity of the baby was shown to be absent. The other pregnancy was terminated, and examination of fetal tissues by biochemical studies confirmed the diagnosis. This experience substantiates the concept that prenatal diagnosis of disorders of galactose metabolism is feasible.

Medical genetics for the otorhinolaryngologist.

Genetic disorders involving the ear, nose and throat can be looked at in essentially the same way that one would view other genetic problems. It is important to differentiate genetic disorders from those due to environmental influences. This may be difficult on clinical grounds, since similar clinical features may be produced by different environmental factors or by different genes or groups of genes. When the cause of the disorder can be established, the risks involved in a family having further offspring usually can be determined reasonably readily. In the uncharacterized situations, empiric risk figures are employed. Abnormalities of genetic origin fall into one of three main groupings: chromosomal abnormalities, single gene mutations or polygenic inheritance. These situations are discussed and examples are given.

Developmental aspects of galactosemia from infancy to childhood.

The developmental status of 60 galactosemic infants, their subsequent intellectual level, school status, visual-perceptual skills, and EEG results were analyzed. In addition, the intelligence of the parents and the unaffected siblings, as well as the educational and vocational status of the parents, were also investigated. The results reveal that the highest level of mental development was in the preschool age group. The lowest level, and still within normal limits, was in the school-age children. The overall findings are consistent with earlier observations that better progress is found in those individuals whose dietary control is instituted at the youngest age level.