Browsing by Author "Shanley, B. C."

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    Isovaleric acidaemia in two South African children
    (Health & Medical Publishing Group, 1977) Malan, C.; Neethling, A. C.; Shanley, B. C.
    Two siblings who were repeatedly admitted to hospital with acute episodes of vomiting, dehydration and coma were found to be suffering from isovaleric acidaemia. This condition is a rare inherited abnormality of leucine metabolism, which is frequently fatal in the early weeks of life and leads to mental retardation in a high proportion of those who survive early attacks. However, both out patients were of normal intelligence. The clinical presentation, biochemical defect, diagnosis and suggested therapies are reviewed.
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    Neurochemical aspects of porphyria. Studies on the possible neurotoxicity of delta aminolaevulinic acid
    (Health and Medical Publishing Group (HMPG), 1975) Shanley, B. C.; Neethling, A. C.; Percy, V. A.; Carstens, M.
    It has been proposed that delta aminolaevulinic acid (ALA), which is overproduced in the inherited hepatic porphyrias, may be responsible for the neurological manifestations of the acute attacks seen in these disorders. Studies were conducted in rats to test the neurotoxicity of ALA. It was found that, after intraperitoneal or subcutaneous injections, ALA is rapidly eliminated via the kidneys. In nephrectomised animals sustained elevation of blood ALA concentration was demonstrated, but despite this, brain uptake was extremely low. Experiments on incorporation of [4 14C] ALA into brain haem yielded similar information. After intraventricular injection of [4 14C] ALA, significant uptake by brain tissue occurred. The subsequent disappearance of ALA was moderately rapid and was virtually complete within 24 hours. Uptake of [4 14C] ALA was apparently significantly greater in the hypothalamus than in other brain areas. The subcellular distribution of radioactivity did not reveal any preferential uptake by nerve endings. Intraventricular injection of unlabelled ALA revealed definite but transitory neurotoxic effects in doses of 3 micromoles and greater. These include involuntary movements and ataxia. No effect of ALA administration on brain protein synthesis could be demonstrated. It is concluded that ALA does have effects on the nervous system in vivo, but the significance of these effects in relation to the pathogenesis of the neurological manifestations of acute porphyria is questionable.
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    Pathogenesis of neural manifestations in acute porphyria
    (Health & Medical Publishing Group, 1977) Shanley, B. C.; Percy, V. A.; Neethling, A. C.
    At least 4 possible mechanisms may be postulated to explain the neural manifestations of acute porphyria in the hereditary hepatic porphyrias. These are: (i) excessive amounts of porphyrins or porphyrin precursors produced in the liver during acute attacks are transported to the central and peripheral nervous system, where they exert neurotoxic effect; (ii) unidentified metabolites of the aforementioned compounds may be responsible; (iii) in patients with these diseases there may be a metabolic defect in neural haem biosynthesis which is aggravated by precipitating factors, thereby leading to acute neural manifestations; and (iv) the hepatic and nervous system lesions may be metabolically quite unrelated. Each of these possibilities is considered, and evidence is adduced that a genetic defect in haem biosynthesis in the nervous system is the most plausible hypothesis.
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    Porphyrin precursors in blood, urine and cerebrospinal fluid in acute porphyria
    (Health & Medical Publishing Group, 1977) Percy, V. A.; Shanley, B. C.
    Four patients suffering from variegata porphyria were investigated during acute attacks. Porphyrin and porphyrin precursor concentrations were determined in the urine, serum, cerebrospinal fluid (CSF) and stools. Levels of delta-aminolaevulinic acid (ALA) and porphobilinogen were found to be very much lower in CSF than in serum sampled concurrently, and were well below levels at which these substances have been shown to exert effects on neural tissue in vitro. These findings cast doubt on the possibility that ALA or porphobilinogen is responsible for the production of the neural manifestations of acute porphyria.
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    Urinary porphyrins and porphyrin precursors in normal pregnancy. Relationship to urinary total oestrogen excretion
    (Health and Medical Publishing Group (HMPG), 1975) De Klerk, M.; Weideman, A.; Malan, C.; Shanley, B. C.
    The relationship between urinary excretion of porphyrins, porphyrin precursors and total oestrogens in normal pregnancy was investigated. Significant increases in total oestrogen, delta aminolaevulinic acid (ALA) and coproporphyrin (COPRO) excretion were noted. However, no close correlation was found between total oestrogen excretion and urinary output of ALA and COPRO. The results suggest that the observed increases in ALA and COPRO excretion during pregnancy may not simply be the result of steroid mediated induction of hepatic haem biosynthesis, as has been proposed.