Genetic studies in mental subnormality.

Date:
1973
Catalogue details

Licence: Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)

Credit: Genetic studies in mental subnormality. Source: Wellcome Collection.

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    7б GENETIC STUDIES IN MENTAL SUBNORMALITY hereditary ataxia in two families, cerebral diplegia in one and probably Tay-Sachs disease in another ; in a further six families in which the affected siblings had a similar abnormal phenotype the clinical features do not conform to any previously described syndromes. In five families the affected siblings had similar bio¬ chemical abnormalities. In one family there was phenylketonuria and in four other families two or more of the retarded siblings excreted excessive amounts of the same amino acid in the urine. In one of these families who presented with spinocerebellar ataxia, there was an excessive amount of tyrosine in the blood and urine but no increase of other phenolic sub¬ stances in the urine. The absence of clinical or biochemical features of tyrosinaemia, including the absence of p-hydroxyphenylpyruric acid in the urine, distinguishes this abnormality from tyrosinosis and tyrosinaemia. It is suggested that reduced activity of the enzyme L-tyrosine aminotransferase could explain the observed biochemical abnormalities. The other three families with specific amino¬ aciduria excreted excessive quantities of hydroxy- lysine, j8-alanine and i-methylhistidine, respec¬ tively, in their urine. Since there was no excess of these amino-acids in the plasma of these patients, it appears likely that they had specific defects in renal membrane transport. The relation between defects of renal tubular re-absorption of amino acids to the occurrence of mental subnormality has been discussed elsewhere (Benson, Swift and Studdy, 1970). Some of the abnormalities in our survey, such as those of skin pattern, analgesia, digital anomalies and asymmetry, were comparatively minor or difficult to elicit on account of the mental subnormality, and verification often required repeated examination. In surveys of mentally subnormal individuals the proportion of cases found to have clinical abnormalities is likely to vary according to the attention paid to clinical examination. Likewise, the number of cases in which biochemical disturbance can be demonstrated depends on the techniques em¬ ployed. The advantage of employing column chromatography rather than paper chromato¬ graphy for amino-acid analysis was confirmed later when the abnormal urines were retested using the latter technique. Excessive concentra¬ tions of tyrosine, hydroxylysine, i-methylhisti- dine and j8-alanine might easily have been missed on screening by this method. It may be concluded, therefore, that both the selection criteria and the diagnostic methods contributed to the high proportion of cases in which abnormalities were detected. It is possible, however, in theory, that selection of cases occurred prior to their consideration for entry into the investigation by some of the numerous factors that determine the social and medical selection of patients for admission to a long stay in hospital. For example, in Great Britain, including the area of the survey, admis¬ sion to hospital is being requested with increasing frequency for low-grade patients with associated physical handicaps. It is possible that these may have a higher probability of a genetic disorder than high-grade subnormal patients without these complications. Behaviour disorders and psychotic manifestations also create a demand for admission, but their genetic significance is less obvious and it is probable that they do not influence the genetic characteristics of hospital populations except by dilution. Social factors and parental inadequacy as causes for admission might be expected to be more frequent in those families with borderline normal intelligence. Such patients have, however, been excluded by the choice of I.Q,. as one criterion for selection. Inspection of our data suggests that there was no significant influence on selection of our hospital patients by factors discussed above. The high prevalence of genetic disorder detected by the present survey is therefore considered to be due essentially to the two-tier system of selection which has been employed, namely the choice of patients with one or more affected siblings and I.Q,.s of less than 50-60. Of the 66 index cases, 40 are males and 26 females. The proportion of affected males to females is of the same order as that found for patients with similar I.Q.s, as reported by Penrose (1938) who found 386 males and 266 females with I.Q,.s less than 49. The correspond¬ ing figures for the normal siblings of their families are 3f males and 19 females. The possibility that sex-linkage (or sex limitation) in a proportion of families may have contributed