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Biomedical subjects

S K Wadman

Publications and source records attributed to S K Wadman.

At least 127 records · Page 7Linked to original sources
PubMed1978

The variability of metabolite excretion in propionicacidaemia.

Random urine samples from eight patients with propionicacidaemia were analyzed by gas chromatography and mass spectrometry in order to see if a consistent metabolite pattern with a high diagnostic value could be found. However, wide variations were observed. The presence of 3-hydroxypropionate and/or methylcitrate were considered to be diagnostic of propionyl-CoA carboxylase deficiency. In addition, samples from ketotic periods frequently contained 3-hydroxy-n-valerate and 3-oxo-n-valerate.

Amino Acid Metabolism, Inborn Errors↗
PubMed1978

An approach to the restoration of T cell function in a purine nucleoside phosphorylase deficient patient.

A patient with a selective impairment of T cell-dependent immunity based on a purine nucleoside phosphorylase (PNP) deficiency has been treated with transfusions of irradiated erythrocytes and plasma. After each transfusion with PNP-containing erythrocytes a decrease in accumulated nucleosides and their deoxy compounds was observed, whereas uric acid excretion and serum uric acid increased. Lymphocyte counts increased transiently after each erythrocyte and plasma infusion and a partial restoration of T cell-dependent immunity was gradually attained. The pattern of restoration was reminiscent of the immunological reconstitution seen in patients with severe combined immunodeficiencies treated with bone marrow transplantation. Amelioration of T cell-dependent immunity was shown to be related to the metabolic changes. On the basis of the presumed mechanism of lymphocyte intoxication and consequently starvation of intracellular DNA precursors, deoxycytidine was given orally. This did not lead to further improvement in immunological function. However, partial restoration of immunological disturbances in PNP deficiency can be attained by erythrocyte transfusions and evidence is presented that additional pharmacological approaches are possible.

Antibody Formation↗
PubMed1978

Combined deficiency of xanthine oxidase and sulphite oxidase: a defect of molybdenum metabolism or transport?

A child is described who presented in the neonatal period with feeding difficulties, severe neurological abnormalities, lens dislocation of the eyes and dysmorphic symptoms of the head. Routine laboratory investigations revealed a decreased serum urate and a positive sulphite reaction of the urine. Subsequent chromatographic examinations showed xanthinuria and increased excretion of S-sulphocysteine and taurine to be present. In addition, high thiosulphate and low sulphate excretions in the urine were observed. Xanthine oxidase deficiency was demonstrated in a jejunal biopsy specimen, whereas the excretion of sulphur containing substances was considered to be characteristic of sulphite oxidase deficiency. This new combination of defects may be the result of malfunctioning of both enzymes, possibly caused by alterations in the essential molybdenum containing active centre of the enzymes, which they share in common.

Abnormalities, Multiple↗
PubMed1978

Familial hyperlysinaemia due to L-lysine alpha-ketoglutarate reductase deficiency: results of attempted treatment.

A mentally retarded male infant with persistent hyperlysinaemia due to L-lysine alpha-ketoglutarate reductase deficiency is described. The effect of dietary restriction of lysine on his mental and behavioural development was examined. By restricting daily dietary lysine to 5.5 mg/kg body weight the fasting serum lysine became normal. Urinary lysine also became normal and the secondary metabolites homocitrulline, homoarginine, N alpha-acetyllysine and N epsilon-acetyllysine were no longer detected. After control of serum lysine for 2.5 y it was felt that the patient's social behaviour, but not his mental development, had improved somewhat.

Adolescent↗
PubMed1978

Deranged isoleucine metabolism during ketotic attacks in patients with methylmalonic acidaemia.

Two patients with methylmalonic acidaemia due to methylmalonyl-CoA mutase deficiency were studied for several years. Both exhibited at least two attacks of severe ketoacidosis, during which they excreted, in addition to methylmalonic acid, a number of abnormal compounds: 3-hydroxypropionic acid, 2-methyl-3-hydroxybutyric, 3-hydroxy-n-valeric acid, 3-oxo-n-valeric acid, 2-methyl-3-oxobutyric acid, citraconic acid and N-tiglyglycine. These compounds represent partly intermediary metabolites from the isoleucine degradation pathway and partly secondary metabolites of propionyl-CoA and tiglyl-CoA.

Acidosis↗
PubMed1978

Effects of thiamine in a patient with a variant form of branched-chian ketoaciduria.

A boy with the intermediate variant of branched-chain ketoaciduria was studied. Treatment with an amino acid mixture was discontinued at the age of 7.5 years. Reintroduction of normal protein-containing foods precipitated the biochemical abnormalities, characteristic of MSUD, which were relieved by 10 mg thiamine/day. Adaptation to this regiment developed and thiamine intake was increased to 100 mg/day, later to 1 000 mg/day. The patient developed well and had no attacks of ketoacidosis. 1-14C-leucine degradation in intact fibroblasts was 15% of controls and did not increase upon addition of thiamine to the incubation medium.

Amino Acids↗
PubMed1977

(2-Ethoxyethoxy)acetic acid: an unusual compound found in the gas chromatographic analysis of urinary organic acids.

An unknown acidic compound was detected in a number of urine samples from patients with a suspected metabolic disorder and some patients treated with chemotherapy. The structure of this compound has been characterized as (2-ethoxyethoxy)acetic acid, using a gas chromatography/mass spectrometry/computer system. The authentic compound was synthesized and compared with the unknown. Urinary (2-ethoxyethoxy)acetic acid is assumed to be formed endogenously from an exogenous precursor, probably 2-(2-ethoxyethoxy)ethanol.

Acetates↗
PubMed1977

Purine nucleoside phosphorylase deficiency associated with selective cellular immunodeficiency.

We studied a 15-month-old girl who had normal T-cell and B-cell immunity at birth, after which a gradual decrease in T-cell immunity developed. This selective cellular immunodeficiency was inherited as an autosomal recessive trait: two older sisters had the same immunodeficiency. Adenosine deaminase activity was present in erythrocytes and lymphocytes of the patient, parents and a healthy brother. Purine nucleoside phosphorylase activity was not found in the patient's erythrocytes and lymphocytes (the parents and brother had intermediate values, indicating that the enzyme deficiency too was inherited as an autosomal recessive trait). Analysis of serum and urine from the patient and of serum from her two deceased sisters showed high levels of inosine and guanosine in addition to hypouricemia and hypouricosuria. The bone marrow was megaloblastic, and the blood hypochromic microcytic. The patient had spastic tetraparesis. Intoxication of the T lymphocytes after birth by metabolic products may explain the progressive cellular immunodeficiency.

B-Lymphocytes↗
PubMed1977

A patient with purine nucleoside phosphorylase deficiency: enzymological and metabolic aspects.

1. Enzymological and metabolic data in a patient with nucleoside phosphorylase (NP) deficiency are described. 2. Incubation of intact NP-deficient red cells with [14C]adenosine showed a rapid uptake and conversion to inosine. Almost no radioactivity was incorporated in the adenosine nucleotides and no hypoxanthine labeling could be detected. 3. Incubation with [14C]inosine resulted in a rapid conversion to IMP in the normal intact red cells but in an accumulation of inosine in the medium with the erythrocytes of the patient, proving again that a NP deficiency is present. 4. The high PRPP level found may result from impaired consumption due to lack of substrates for the salvage enzyme HGPRT. 5. Incubation with [14C]hypoxanthine and [14C]adenine showed that normal HGPRT and APRT activities were present in the NP-deficient red cells. 6. In serum and urine of the patient the levels of inosine and guanosine were considerably increased, while the serum and urinary levels of uric acid were very low. In the two deceased sisters NP deficiency was also strongly suggested by analyses of the serum purines, of stored deep frozen samples.

Adenine↗
PubMed1977

Hereditary mitochondrial myopathy with lactic acidemia, a De Toni-Fanconi-Debré syndrome, and a defective respiratory chain in voluntary striated muscles.

A patient suffering froma mitochondrial myopathy leading to severe insufficiency of the voluntary muscles is described. Severe cerebral damage was present. Major biochemical symptoms were extreme lactic acidemia, hypophosphatemia and hyperphosphaturia, and generalized aminoaciduria, renal glucosuria, and polyuria. Muscular insufficiency resulted in lethal asphyxiz. All therapeutic trials were insufficient. The patient and two other children of the same family with a similar clinical picture all died before the 4th month of life. The condition is probably inherited in an autosomal recessive way. A defective respiratory chain in the mitochondria of the striated muscles is proposed as the underlying mechanism. Cytochromes aa3 were absent, b was nearly absent, but cc1 was present. In heart muscle cytochromes aa3 and b were at the level of the controls.

Cytochromes↗