Urinary Delta-aminolaevulinic Acid Research Articles

Occupational lead intoxication from terracotta tiles manufacturing: a case study

Abstract We report the case of a 63-year-old terracotta tiles manufacturer who presented with acute abdomen and normocytic anaemia. The patient presented with elevated levels of urinary delta-aminolaevulinic acid without any increase in the levels of urine porphobilinogen or urine coproporphyrin. Detection of elevated lead blood levels (1939 µg/dL one month before hospital admission in the occupational medicine clinic and 44.70 µg/dL at hospital admission, values come from two different laboratories) confirmed the diagnosis of chronic lead poisoning due to occupational exposure. Chelation therapy with D-penicillamine resulted in the improvement of clinical symptoms and lead blood levels. Clinicians should be aware that lead poisoning caused by occupational exposure can still occur sporadically in terracotta tiles manufacturing workers, lead poisoning being a neglected diagnosis in abdominal pain.

Dual gene defects involving δ‐aminolaevulinate dehydratase and coproporphyrinogen oxidase in a porphyria patient

Summary A Caucasian male had symptoms of acute porphyria, with increases in urinary delta-aminolaevulinic acid (ALA), porphobilinogen (PBG) and coproporphyrin that were consistent with hereditary coproporphyria (HCP). However, a greater than expected increase in ALA, compared with PBG, and a substantial increase in erythrocyte zinc protoporphyrin, suggested additional ALA dehydratase (ALAD) deficiency. Nucleotide sequence analysis of coproporphyrinogen oxidase (CPO) cDNA of the patient, but not of the parents, revealed a novel nucleotide transition G835-->C, resulting in an amino acid change, G279R. The mutant CPO protein expressed in Escherichia coli was unstable, and produced about 5% of activity compared with the wild-type CPO. Erythrocyte ALAD activity was 32% of normal in the proband. Nucleotide sequence analysis of cloned ALAD cDNAs from the patient revealed a C36-->G base transition (F12L amino acid change). The F12L ALAD mutation, which was found in the mother and a brother, was previously described, and is known to lack any enzyme activity. This patient thus represents the first case of porphyria where both CPO and ALAD deficiencies were demonstrated at the molecular level.

Acute intermittent porphyria in childhood: a population‐based study

To establish age-adjusted reference intervals of urinary delta-aminolaevulinic acid (U-ALA) and porphobilinogen (U-PBG) in children, and to analyse the frequency and type of clinical manifestations of acute intermittent porphyria (AIP) in childhood. Concentrations of U-ALA and U-PBG in healthy children aged 3-16y were analysed. In a population-based study in northern Sweden of 61 children aged < 18 y with DNA-verified AIP, the clinical manifestations of AIP in childhood were analysed prospectively (up to 2.5 y). Initially the children underwent a standardized investigation (anamnesis, physical examination, laboratory tests). Instructions were issued to keep a structured diary and to provide urine samples for ALA and PBG analyses in all situations of suspected AIP attacks (prospectively). Reference intervals for U-ALA and U-PBG showed age-group variations in children. Baseline levels of U-ALA and U-PBG are increased in gene carriers, one-quarter of them exceeding the 90th percentile of age- and gender-matched controls. Baseline levels did not distinguish symptomatic from non-symptomatic children in a short-term perspective. Clinical evidence of AIP attacks was found in 10% of child AIP gene carriers; in all cases the first attack occurred before the age of 15 y. AIP symptoms in children may be vague and of short duration and U-ALA and U-PBG levels are often elevated only slightly or not at all; thus, symptoms and signs may differ from those in adults. Children of AIP gene carriers should be DNA tested, followed up and carefully instructed on preventive measures to avoid developing manifest AIP.

Testing the porphyrinogenicity of propofol in a primed rat model

We evaluated the porphyrinogenicity of propofol in a rat model. After a pilot study had been conducted to determine an optimal dose, 48 fasting male Sprague-Dawley rats were allocated randomly to six groups. The animals in groups 1-3 received saline i.p. In groups 4-6, the animals were given allylisopropylacetamide (AIA). Twelve hours later, animals in groups 1 and 4 received saline, groups 2 and 5 were given propofol 150 mg kg-1 i.p., followed by 75 mg kg-1 3 h later, and groups 3 and 6 received phenobarbitone 50 mg kg-1 i.p. and 25 mg kg-1 i.p. The animals were anaesthetized and killed 3 h after the second drug bolus and we measured the concentration of cytochrome P450, total porphyrin content and the activity of delta-aminolaevulinic acid synthase (ALAS) in the liver. Urinary delta-aminolaevulinic acid (ALA) and porphobilinogen (PBG) concentrations were measured. Analysis of variance and the t test with Bonferroni's correction were used to compare data. The hepatic cytochrome P450 concentration in the non-primed groups varied from 28.1 to 31.1 nmol g-1; administration of AIA decreased this to 20.1-20.9 nmol g-1. Total hepatic porphyrins were between 0.78 and 1.22 nmol g-1 in the non-primed groups and between 2.71 and 3.54 nmol g-1 in the AIA-primed groups. Hepatic ALAS activity was 29.2 and 35.5 nmol h-1 g-1 in groups 1 and 2. In the primed saline group, ALAS activity was measured at 134.5 nmol h-1 g-1.(ABSTRACT TRUNCATED AT 250 WORDS)

Evaluation of delta-aminolaevulinic acid excretion in random urine samples of children

Urinary delta-aminolaevulinic acid (delta-ALA) excretion was evaluated in random urine samples of 191 healthy children, aged 2-14 years, with blood lead levels < 0.8 mumol/l (mean +/- SD: 0.34 +/- 0.13), erythrocyte zinc-protoporphyrin < 70 mumol/mol haem (mean +/- SD: 50.4 +/- 8.0) and blood haemoglobin > 6.8 mmol/l (mean +/- SD: 8.2 +/- 0.5). It was found that uncorrected delta-ALA concentration and delta-ALA/creatinine ratio are age-dependent, whereas the ratio of delta-ALA/logarithm of creatinine concentration (mean +/- SD: 55.3 +/- 13.5 mumol/log mmol) is independent of age and sex. The authors recommend the use of this parameter for the assessment of delta-ALA excretion in random urine samples in children.

Influence of the degree of exposure to lead on relations between alcohol consumption and the biological indices of lead exposure: epidemiological study in a lead acid battery factory.

Alcohol has been shown to interact with lead to influence haem biosynthesis. The aim of this study was to define the dependence of this interaction on the degree of exposure to lead. Exposure to alcohol was estimated by measurement of alcohol concentrations in a sample of urine collected during the morning (AlcUM) (0.82 (SD 4.36) mmol/l) and in a sample collected during the afternoon (AlcUA) (1.15 (SD 3.49) mmol/l). The biological monitoring of exposure to lead included measurements of blood lead (Pb-B) (1.82 (SD 0.72) mumol/l), urinary delta-aminolaevulinic acid (ALAU) (35.33 (SD 28.00) mumol/l; d = 1.015), and erythrocyte zinc-protoporphyrin (ZPP) (112.90 (SD 83.71) nmol/mmol Hb) concentrations. The study of the influence of the degree of occupational exposure to lead on relations between alcohol consumption and effects of the exposure to lead led to the consideration of two different groups--namely, mildly and strongly exposed subjects. In the first group, individual biological susceptibility seemed to play a preponderant part. In the second, the pool of lead present in the body seemed to be sufficiently important to mask the effects of individual susceptibility.

Relation between urinary beta-aminoisobutyric acid excretion and concentration of lead in the blood of workers occupationally exposed to lead.

Urinary beta-aminoisobutyric acid (ABA) concentration was determined by fluorometric high performance liquid chromatography in 22 workers occupationally exposed to lead. The urinary excretion of ABA was increased with increasing exposure to lead. The excretion of urinary ABA had a significant correlation with concentration of lead in blood (Pb-B) (r = 0.581), similar to the correlation of Pb-B with urinary delta-aminolaevulinic acid (ALA) concentration (r = 0.563). The determination of urinary ABA concentration in workers exposed to lead, therefore, may offer a new approach for evaluating the health effect of lead.

LHRH Analogue Treatment for the Prevention of Premenstrual Attacks of Acute Porphyria

We have assessed the value of suppressing ovulation with the luteinizing hormone releasing hormone (LHRH) analogue buserelin in seven patients experiencing crises of acute intermittent porphyria related to the menstrual cycle. Clinical course, plasma oestradiol and progesterone levels, and urinary porphyrin and precursor excretion were monitored over a baseline period of approximately one year, and then for a similar period on buserelin treatment. There was a trend towards clinical improvement on buserelin therapy. The median number of attacks fell from seven during the baseline period to three on treatment (p = 0.06). The response to buserelin varied considerably, with those patients in whom the association between baseline attacks and the menstrual cycle was strongest gaining the most benefit. All patients became amenorrhoeic with suppression of plasma oestradiol and progesterone levels. Urinary delta-aminolaevulinic acid and total porphyrin excretion fluctuated widely both before and during treatment. Our experience indicates that ovulation suppression may be of value in the management of young women in whom recurrent attacks of porphyria are related to the menstrual cycle.

High accuracy (stable isotope dilution) measurements of lead in serum and cerebrospinal fluid.

The concentration of lead in blood, serum, cerebrospinal fluid, and urine was measured in patients with neurological disease and in control subjects including cases of plumbism. A plot of blood lead versus serum lead resembles the familiar curves of blood lead versus either free erythrocyte porphyrin or urinary delta-aminolaevulinic acid in that serum lead is constant up to a blood lead concentration of 40 micrograms/dl (2 mumol/l) and rises steeply thereafter. The serum lead concentrations yield renal clearances in the range 5-22 ml/min in agreement with values obtained with radiolead on man and predicted from animal studies. The lead content of cerebrospinal fluid is consistently less than that of serum, averaging 50% of the serum concentration for blood leads of less than 20 micrograms/dl (1 mumol/l) but rising to 80-90% in cases of plumbism. Patients with motor neurone disease could not be distinguished from those with other neurological diseases on the basis of the lead content of their serum or cerebrospinal fluid.

Behaviour of indicators of exposure and effect after cessation of occupational exposure to lead.

The behaviour of blood lead (PbB) and of some indicators of effect (erythrocyte protoporphyrin IX (EP), delta-aminolaevulinic acid dehydratase activity of erythrocytes (ALAD), and urinary delta-aminolaevulinic acid (ALAU)) were studied in subjects who had ceased working with inorganic lead for at least one year. Relations between these indices and chelatable lead (PbU-EDTA (lead in urine after injection of CaNa2 EDTA 1 g intravenously)), a test that is used to evaluate the lead deposits in the body, were also analysed. As a comparison, a group of subjects currently exposed was studied. In the workers with past exposure the PbB values were significantly lower, at the same PbU-EDTA levels, than those found in subjects at work. The relation between EP and PbU-EDTA shows that, corresponding levels of chelatable lead, the values of the erythrocyte metabolite are identical in the two groups. Considering the EP-PbB relation, however, at the same PbB levels the protoporphyrin values appear distinctly more altered in the subjects with past exposure. Similar results were obtained from a study of the relations between ALAD and PbU-EDTA and between ALAD and PbB. The relation between ALAU and PbU-EDTA, however, shows that, at the same PbU-EDTA levels the urinary metabolic in past-exposed subjects is distinctly lower than in subjects at work, while the relation between ALAU and PbB shows that, for similar blood lead values, the ALAU levels are identical. On the basis of the results obtained it is concluded that in subjects with past exposure, EP and ALAD can be used in establishing the persistence and extent of an "active deposit" of lead in the organism, while PbB is of very limited use.

A simple and rapid one-tube method for the determination of urinary delta-aminolaevulinic acid.

A simple and rapid one-tube method for the determination of urinary delta-aminolaevulinic acid.

Control of lead workers by determination of urinary delta-aminolaevulinic acid.

The output of δ-aminolaevulinic acid (ALA) and of creatinine was determined in lead workers. Values from 24-hour specimens were compared with values from specimens voided at the time of examination. Highly significant positive correlations were found between the output of ALA and of creatinine in both sets of specimens. The individual spreads, however, were considerable. Values for ALA in mg./100 ml. urine and ALA in mg./g. creatinine were strongly correlated in fresh specimens as well as in 24-hour specimens. When values for ALA in mg./100 ml. urine were compared with ALA in mg./g. creatinine, an approximate relationship of 1:5 was found in the range 1.0-3.0 mg. ALA/100 ml. urine, <i>i.e.,</i> the mean urinary concentration of creatinine was 0.2 g./100 ml. It is concluded that the collection of 24-hour specimens is not necessary and also that reference to creatinine appears to have no advantage over the simple expression of ALA in mg./100 ml. urine. This must be due to the fact that the influence of the metabolic activities of lead has a greater effect on the urinary concentration of ALA than has the concentration of urine in the kidneys.

606. Porphyrins and lead exposure: de Kretser, A. J. & Waldron, H. A. (1963). Urinary delta amino-laevulinic acid and porphobilinogen in lead-exposed workers. Brit. J. industr. Med.20, 35

606. Porphyrins and lead exposure: de Kretser, A. J. & Waldron, H. A. (1963). Urinary delta amino-laevulinic acid and porphobilinogen in lead-exposed workers. Brit. J. industr. Med.20, 35

Urinary Delta Amino-Laevulinic Acid and Porphobilinogen in Lead-Exposed Workers

Of 100 workers exposed to lead in varying degrees, 34 had a urinary delta amino-laevulinic acid (ALA) concentration of above 0·6 mg./100 ml. and a further 35 had an ALA concentration of between 0·3 mg. and 0·6 mg./100 ml. In only 20 of the workers was the urinary porphobilinogen concentration above 0·1 mg./100 ml., two of these being above 0·2 mg./100 ml. No significant correlation was found between the urinary concentration of ALA and coproporphyrin, nor was there correlation between the ALA and urinary lead levels, in fact the highest level of ALA was associated with a urinary lead of less than 200 μg./litre. A raised urinary lead was always associated with a raised ALA.