Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0025362 (mental retardation)
 15,878 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The Richner-Hanhart syndrome corresponds to a tyrosine elevation in serum due to deficit in soluble tyrosine aminotransferase in liver cells. This new enzymopathy which is transmitted in an autosomal recessive mode is called oculocutaneous tyrosinosis. It is curable by a poor diet in tyrosine and its precursors. The diagnosis has been invoked in a 18 months old girl, on the association of punctuate palmar and plantar keratosis, dentritic ulcerated keratitis, and mental retardation. The diagnosis is confirmed by elevation of tyrosinemia to 52 mgs/100 mls associated with a high urinary elimination of tyrosine and plenylcetonic acid. Absences of anomaly in the metabolism of methionin and hepatorenal absence of disturbance of hepatorenal system is characteristic. The keratosis accompany orthokeratotic hyperkeratosis. The keratinocytes show 2 types of anomaly ranged in strates in the epiderm. Intracytoplasmic vacuoles which include or lead to pseudomyelinic formations extend progressively from the mitochondrial alterations in the epidemial basal layers. Bulky polyhedral electron dense particles are found in the cytoplasm of the superficial keratinocytes. Most of these aspects have been demonstrated anteriorly in the keratinocytes and the cornea; on the other hand, signs of mitochondrial sulferance had not been observed. The genesis of these cellular alterations based on the liberation of lysosomial enzymes by the action of crystals of tyrosine has been suggested by Goldsmith from experimental facts. However, it seems the mitochondrial defect occurs outside this mechanism.
 ...
PMID:[Oculo-cutaneous tyrosinosis (Richner-Hanhart syndrome). Histo-pathological study of a case]. 611 39

Richner-Hanhart's syndrome (corneal dystrophies, palmoplantar keratoses, and mental retardation) is caused by high levels of L-tyrosine in the blood, probably due to a defect of soluble tyrosine aminotransferase. Biopsies of skin lesions of 3 cases revealed peculiar ultrastructural changes that were not found in controls and have not been recorded before. Thickening of the granular layer and increased synthesis of tonofibrils and keratohyalin occurred in all cases. In the ridged palmar or plantar skin large numbers of microtubules and unusually tight packing of tonofibrillar masses were regularly demonstrable, the latter containing tubular channels or inclusions of microtubules. It is assumed that increased cohesion and tight packing of tonofilaments could prevent normal spreading of keratohyalin and result in its globular appearance. No crystal formation was observed in epidermal keratinocytes nor was there lysosomal damage. A biochemical model to correlate these ultrastructural findings to known biochemical and clinical features is proposed. It is suggested that excessive amounts of intracellular tyrosine enhance cross-links between aggregated tonofilaments and modulate the number and stability of microtubules.
 ...
PMID:Richner-Hanhart's syndrome: ultrastructural abnormalities of epidermal keratinization indicating a causal relationship to high intracellular tyrosine levels. 612 75

The present paper reviews most of the research on mental retardation in Norway, published in 1970-1980. An important part of this work is represented by Hole's reports of experimental phenylketonuria (PKU) in the rat and studies on peptides and protein-associated peptide complexes in mental disturbances, including experimental studies of effects on brain function and behavior of a peptide fraction (factor 3 b 2). Among studies on diseases with mental retardation, are determinations of arylsulphatase A in cultured amniotic fluid cells and in amniotic fluid as measures of prenatal diagnosis of metachromatic leukodystrophy, reports on screening disorders of tyrosine metabolism and the occurrence of positive dye test in blind children and patients with physical and mental handicaps. Further, studies on the effects of antiepileptics on immunoglobulins are reported. In the fields of social medicine, psychology and psychiatry, only few studies have been published in international journals. Brief reports on Norwegian articles comprise studies on work and disability, social and psychological handicaps in special school pupils, psychosis in mental retardation, and some efforts to design psychological treatment programs for the mentally retarded. The majority of research on mental retardation or with relevance to this field in Norway, has either been supported by the Norwegian Council for Research on Mental Retardation, or the Norwegian Research Council for Science and the Humanities. Based on annual reports of these councils, and correspondence to centers involved in such research, we have collected reports published in the period 1970 to 1980. We have also received unpublished reports, but have chosen not to include most of them in this review, because of the difficulties for the readers to obtain these reports. The institutional and noninstitutional services for the mentally retarded in Norway have no formal connection with university or other research institutes. Nevertheless, most of the research papers have been submitted from such institutes. Most of the reports traced are in the fields of basic neurobiology, medicine, and psychology, and will be dealt with under these headings.
 ...
PMID:Research on mental retardation in Norway 1970-1980: a review. 635 79

Four cases of tyrosinaemia with cutaneous manifestations, but without ocular involvement, are reported in a family with consanguineous parents. The tyrosine levels in the serum and in the urine were normal in both parents, while in the offsprings the tyrosine levels were elevated 7 1/2-13 times in the serum and 3-13 times in the urine. Although the serum tyrosine levels in our cases were higher than most of the cases reported in the literature the eyes of all our patients were normal. The skin manifestations were very impressive, and varying degrees of mental retardation were present in all patients. The patients put on a low-protein diet improved considerably and have been kept symptom-free for 1 1/2 years. The possible implication of the discrepancy between the high serum levels and lack of ocular changes is discussed. Our results suggest that the Richner-Hanhart syndrome may include more than one distinct biochemical entity.
 ...
PMID:Richner-Hanhart syndrome (tyrosinaemia-II) (report of four cases without ocular involvement). 645 6

Three children (6 eyes) with systemic tyrosinemia who presented with a diagnosis of herpes simplex keratitis are described. Two of the patients underwent extensive treatment for herpes simplex keratitis until their defects in tyrosine metabolism were discovered. All three children responded favorably to a low-tyrosine diet. These cases illustrate the typical corneal findings of the Richner-Hanhart syndrome (pseudodendritic keratitis, hyperkeratotic skin lesions of the palms and sole without mental retardation). The findings in these three patients were similar to those cases previously reported in the literature except none had mental retardation. The ophthalmologist confronted with a young child with bilateral dendritiform keratitis should request evaluation of the serum tyrosine levels.
 ...
PMID:Pseudodendritic keratitis and systemic tyrosinemia. 645 71

The "justification hypothesis" attributes mental retardation in phenylketonuria (PKU) to an inability of the heterozygous mother to deliver an appropriate amount of tyrosine to the PKU fetus who, in turn, is unable to correct for this deficiency because of its genetic constitution. We tested this hypothesis by measuring concentrations of tyrosine and phenylalanine in cord blood obtained at delivery from nine infants with PKU and five infants with persistent (non-PKU) hyperphenylalaninemia (PHP). For each of these specimens there were four control cord-blood specimens from infants born on the same day and, generally, in the same hospital. PKU and PHP groups were similar with respect to cord-blood tyrosine and phenylalanine values. There was no biologically significant deficiency of tyrosine in cord blood of the pooled PKU and PHP deficiency of tyrosine in cord blood of the pooled PKU and PHP groups (54 +/- 10 microM, mean +/- SD) compared with controls (61 +/- 16 microM, P = 0.13). On the other hand, phenylalanine in cord blood of the pooled PKU and PHP groups was significantly increased (144 +/- 30 microM, mean +/- SD) compared with controls (128 +/- 24, P = 0.004). The mangitude of the differences in cord-blood tyrosine and phenylalanine between control and PKU subjects are so small that it is unlikely that they have any consequences for physical and mental development. The justification hypothesis, as it pertains to blood tyrosine at term, is not upheld.
 ...
PMID:Cord-blood tyrosine levels in the full-term phenylketonuric fetus and the "justification hypothesis". 693 44

The Richner-Hanhart syndrome corresponds to a tyrosine elevation in serum due to a defect in soluble tyrosine amino-transferase in liver cells. This new enzymopathy which is transmitted in an autosomal recessive mode is called oculo-cutaneous tyrosinosis. It is curable by a low diet in tyrosine and its precursors. The diagnosis has been clinically suggested in an 18 months old girl, by the association of punctate palmar and plantar keratosis, dendritic ulcerated keratitis, and mental retardation. The diagnosis was established by elevation of tyrosinemia up to 52 mg/100 ml associated with a high urinary elimination of tyrosine and phenylcetonic acid. Absence of anomaly in the metabolism of methionin and hepatorenal lesion is characteristic. The diagnosis was confirmed by the absence of soluble tyrosine aminotransferase in liver cells and by the effectiveness of the diet. The clinical keratosis corresponds histologically to a orthokeratotic hyperkeratosis. The keratinocytes show 2 types of anomalies ranged in the epiderm. Intracytoplasmic vacuoles which include or lead to pseudomyelinic formations extend progressively from the mitochondrial alterations in the epidemial basal layers. Bulky polyhedral electron dense particles are found in the cytoplasm of the superficial keratinocytes. Most of these images have been demonstrates anteriorly in the keratinocytes ant the corned; on the other hand, signs of mitochondrial anomaly had not been observed. The genesis of these cellular alterations based on the liberation of lysosomial enzymes by the action of crystals of tyrosine has been suggested by Goldsmith from experimental facts. However, it seems that the mitochondrial defect occurs outside this mechanism.
 ...
PMID:[Changes in the keratinocytes in oculo-cutaneous tyrosinosis: Richner-Hanhart syndrome (author's transl)]. 723 83

Richner-Hanhart syndrome (Tyrosinemia Type II) is an autosomal recessive disorder of amino acid metabolism characterized by ocular changes, painful palmoplantar hyperkeratosis, and mental retardation. Serum tyrosine increases due to tyrosine aminotransferase deficiency resulting in the deposition of tyrosine crystals in the cornea and in corneal inflammation. Patients are often misdiagnosed as having herpes simplex keratitis. We report on a child who presented with bilateral keratitis secondary to Tyrosinemia Type II diagnosed as herpes simplex keratitis.
 ...
PMID:Richner-Hanhart syndrome (tyrosinemia type II). Case report and literature review. 764 39

Richner-Hanhart syndrome, also called oculo-cutaneous tyrosinosis type II, is a recessive autosomal genodermatosis consecutive to a disorder of tyrosine metabolism. It presents as a varying association of palmo-plantar keratosis, bilateral keratitis and mental retardation. The authors report a new case which is atypical in that palmoplantar keratosis made a late appearance. The diagnosis was confirmed by the presence of hypertyrosinaemia, hypertyrosinuria and urinary excretion of phenolic acids, and the absence of hepato-renal lesion. Needle biopsy of the liver, which demonstrates the deficiency of soluble cytosolic tyrosine aminotransferase, is not indispensable to the diagnosis and was not performed in our patient. Treatment consisted of a dietary measure: a controlled phenylalanine and tyrosine intake to obtain a tyrosinaemia below 10 mg/100 ml. This resulted in a favourable and durable course of the oculo-cutaneous lesions. In case of isolated skin lesion, retinoids can be prescribed either alone of combined with a diet, making it less strict.
 ...
PMID:[Oculocutaneous type II tyrosinosis]. 836 6

Maternal phenylketonuria (PKU) represents a high risk for birth defects, including mental retardation, in offspring. Thus, it could cancel gains represented by the prevention of PKU-induced mental retardation in the current generation. Effective dietary treatment of maternal PKU pregnancies could avoid this potentially tragic occurrence. However, dietary compliance is often difficult because a necessary component of the diet, medical nutritional formulas, often have an unpleasant taste and odour. We treated the second pregnancy of a phenylketonuric women who had required extended hospitalization during her first pregnancy because of poor formula tolerance, and who had similar difficulty in the second pregnancy. To alleviate this problem, we developed a system whereby she could pack the formula into gelatin capsules for ingestion. Packing and ingestion of 20 capsules required less than 30 minutes three times a day. With capsules her blood phenylalanine level was almost always within the recommended range of 120-360 mumol/L (2-6 mg/dl) and hospitalization was not required. The phenylalanine content of the capsules was easily accommodated by a small reduction in allowable food. Other amino acid levels, including tyrosine and other essential nutrient levels, were normal. We believe that using gelatin capsules for formula ingestion can be very beneficial in the management of maternal PKU pregnancies and could be extended to the dietary treatment of other inborn errors of metabolism.
 ...
PMID:The use of gelatin capsules for ingestion of formula in dietary treatment of maternal phenylketonuria. 848 91


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>