1 The Renal Unit, Antrim Area Hospital, and 2 The Department of Neurology, Belfast City Hospital, Northern Ireland
Keywords: acute renal failure; acylcarnitines; myoglobinuria; rhabdomyolysis; very-long-chain acyl coenzyme A dehydrogenase deficiency
![]() |
Introduction |
---|
![]() ![]() ![]() ![]() ![]() |
---|
We describe the case of a man with VLCAD deficiency who presented for the first time at the age of 41 with muscle pains, dark urine, and renal failure. We believe this to be only the second published case of VLCAD deficiency presenting in adult life as acute renal failure requiring dialysis.
![]() |
Case |
---|
![]() ![]() ![]() ![]() ![]() |
---|
The patient gave a history of developing marked muscle pains after moderate exercise over the past 20 years, often followed by the presence of dark urine. On this occasion the muscle pains were more severe and the dark urine slower to clear than usual. Past medical history included only two episodes of acute gout. He took no medications, was an ex-smoker of 5 years, and drank 10 units of alcohol per week.
On examination he was apyrexic and clinically euvolaemic. Blood pressure was 160/82 mmHg; pulse 80 b.p.m., regular. Full power was present in all muscle groups, with normal tone, reflexes and sensation.
Dipstick urinalysis revealed large amounts of proteinuria and haematuria. Laboratory values were as follows: sodium 139 mmol/l (normal range 136146), potassium 4.5 mmol/l (3.55.2), chloride 92 mmol/l (95108), bicarbonate 29 mmol/l (2230), urea 29.9 mmol/l (2.36.6), creatinine 776 µmol/l (70180), glucose 6.9 mmol/l (46). Haemoglobin 13.3 g/dl (1217), leukocytes 10.5x109/l (411), platelets 238x109/l (150400), creatine kinase 177 600 U/l (25180), creatine kinase (MB fraction) 540 U/l (=0.03%), aldolase 22.2 U/l (1.27.6), Lactate dehydrogenase 5084 U/l (240525), aspartate transaminase 4520 U/l (540), alanine aminotransferase 1200 U/l (540). Other liver function tests were within normal limits. Arterial blood gases, chest X-ray, and ECG showed no abnormalities.
Total urinary protein excretion was 0.3 g/24 h (<0.15). Urine microscopy revealed two red cells per mm3 with 50 white cells per mm3. There was no growth on repeat urine cultures. The presence of urinary myoglobin was confirmed by spectroscopy and precipitation.
A diagnosis of acute renal failure secondary to rhabdomyolysis and myoglobinuria was made. He remained oliguric and 2 days after admission blood urea had risen to 45.1 mmol/l and serum creatinine to 1039 µmol/l. A subclavian catheter was inserted and haemodialysis commenced. Six haemodialysis sessions over a 2-week period were required. Urine output began to increase after 11 days and had increased to 3 l/day at 2 weeks.
The patient was discharged after 17 days, dialysis independent, with a blood urea of 19.2 mmol/l, and creatinine of 838 µmol/l. Renal function steadily improved and at 3 months blood urea was 6.5 mmol/l, and creatinine 145 µmol/l.
Further investigations were undertaken to determine the precise cause of this patient's rhabdomyolysis. Fasting resting lactate was normal at 1.9 mmol/l. Blood ammonia was normal at 25 µmol/l. DNA analysis for dystrophin gene deletion was negative. Muscle biopsy was not diagnostic, showing non-specific minor myopathic features. Immunocytochemical staining for both dystrophin I and II and spectrin was positive in all fibres. There were no inclusions or mitochondrial abnormalities, and myofibrils were intact. Endomysial collagen was not increased.
Blood acylcarnitine levels were measured by mass spectrometry (a) and the following abnormal results obtained:
![]() | (001) |
![]() | (002) |
Fibroblasts were cultured from a skin biopsy and tritium release assays of fatty acid ß-oxidation performed using [9,10-3H]myristate and [9,10-3H]palmitate and [9,10-3H]bleate (b). Results are expressed as nmol per mg protein per hour followed by mean percentage of controls:
![]() | (003) |
The patient has been advised to avoid excessive exercise particularly when fasting, stop exercise if he develops muscle cramps or pain, and maintain a high fluid intake when exercising. He has been advised to take a high-carbohydrate, low-fat diet. He has had no recurrences in the subsequent 2 years. If he continues to follow this advice we would expect a good prognosis.
![]() |
Discussion |
---|
![]() ![]() ![]() ![]() ![]() |
---|
Fatty acids are important muscle substrates, especially when fasting or during prolonged exercise. VLCAD is an enzyme catalysing the dehydrogenation of long-chain fatty acids in the first step of mitochondrial fatty acid oxidation [1]. VLCAD was first identified in 1992 [3]. The human VLCAD gene has been identified and located on the short arm of chromosome 17 between bands p11.2 and p11.13105 [4]. The gene is 5.4 kb long and contains 20 exons [5].
A number of patients with VLCAD deficiency have now been identified. A large study by Vianey-Saban et al. [1] looked at 30 such patients in 27 unrelated families. Two main clinical phenotypes of VLCAD deficiency were described:
The adult presentation of VLCAD deficiency has a milder phenotype presumably because of the presence of some residual enzyme activity. This is only the second report of VLCAD deficiency presenting with acute renal failure requiring dialysis. A greater than usual level of exercise in the fasting state caused excessive rhabdomyolysis and the failure to maintain an adequate fluid intake resulted in acute renal failure in this patient. It is possible that a significant number of cases of rhabdomyolysis which do not have any established aetiology may have discoverable metabolic defects similar to those in this patient. Therefore we would suggest that in such cases enzymatic defects are looked for, so that appropriate advice can be given.
![]() |
Acknowledgments |
---|
![]() |
Notes |
---|
![]() |
References |
---|
![]() ![]() ![]() ![]() ![]() |
---|