1414 THE LANCET

in 20 out of 44 patients. How UDCA decreases enzymes in patientswith chronic HCV hepatitis remains controversial. UDCA mayhave direct cytoprotective effects on the hepatocyte.2,3 Whether thedecrease in serum enzyme levels is followed by an improvement inthe liver histology remains to be seen. Long-term, double-blindstudies are needed to evaluate the effects of UDCA on liver

histology and the ability of the drug to prevent the progression ofHCV-related chronic hepatitis. Might UDCA be a possiblealternative for patients who do not respond to interferon or whoreplase after discontinuation of interferon?

Liver Unit,Marino General Hospital,00141 Rome, Italy

CLAUDIO PUOTIALFONSA PANNULLOGLORIA ANNOVAZZITERESA FILIPPIANDREA MAGRINI

1. Crosignani A, Battezzati PM, Setchell KDR, et al. Effects of ursodeoxycholic acid onserum liver enzymes and bile add metabolism in chronic active hepatitis: adose-response study. Hepatology 1991; 13: 339-44.

2. Galle PR, Theilmann L, Raedsch R, et al. Ursodeoxycholate reduces hepatotoxicity ofbile salts in primary human hepatocytes. Hepatology 1990; 12: 486-91.

3. Heuman DM Mills AS, McCall J, et al. Conjugates of ursodeoxycholate protectagainst cholestasis and hepatocellular necrosis caused by more hydrophobic bilesalts. Gastroenterology 1991; 100: 203-11.

Spinal fusion for low back painSiR,—I am strongly sympathetic to Professor Little’s thoughtful

article (April 3, p 878). Spinal fusion for low back pain is one of the80% of procedures untested by clinical trials. We know from

epidemiological data that the frequency of spinal surgery is closelycorrelated with the number of orthopaedic and neurosurgeons per

head of population and that spinal fusion may be associated with anincreased number of complications and has questionable benefits.Those of us who do use this procedure continue to be encouraged byour patients in whom treatment has been of unequivocal benefit,and discouraged by those in whom an expensive and sometimesdangerous procedure has failed or even has made things worse.Clearly, controlled trials are needed to explore this issue. One of thedrawbacks to establishing such controlled trials are difficulties withdecisionmaking by both the clinician and the patient. Anyone whohas sat in with an "expert" colleague will know that assessment anddecisionmaking is a singularly idiosyncratic process and often atvariance with what one might do oneself. In my view this makes amockery of the ideal proposed by Eddyl of a personal computer onevery clinician’s desk.Then there is the patient. The patient usually makes the final

decision to proceed. Nevertheless, this individual, however

carefully advised, is far from "Homo numericus economicus". Howcan a young or middle aged adult who has tried and failed all theavailable conservative treatments avoid grasping at any straw, evenif the odds are clearly stacked against them? (Homo desperatus?) Thegood clinician has to allow both time to explain and for the patient todecide. This is a process that is far beyond numbers. Clearly, weneed clinical trials, but we may well not receive a convincing answerfrom them.

Nuffield Orthopaedic Centre,Headington,Oxford OX3 7LD, UK J. C. T. FAIRBANK

1. Eddy DM. Medicine, money, mathematics. Am Coll Surg Bull 1992; 77: 36-49.

Defective cholesterol biosynthesis inSmith-Lemli-Opitz syndrome

SIR,-We report two patients with a clinical diagnosis of theSmith-Lemli-Opitz syndrome who have severely abnormalcholesterol metabolism. The syndrome is autosomal recessive andcharacterised by microcephaly, poor growth, dysmorphic features,genital and limb abnormalities, and mental retardation.! In

addition, hypoplasia of frontal lobes, cerebellum, and brainstemhave been noted. Postmortem studies have uncovered many seriousdefects in the brain, including demyelination of cerebral

hemispheres, cranial nerves and peripheral nerves, and neuronal

loss.2 Several associated features, including hepatic dysfunction,renal cysts, adrenal enlargement, epiphyseal dysplasia, and cataractssuggested a biochemical cause.3 Smith-Lemli-Opitz syndrome hasa prevalence of 1 in 40 000.4Our two unrelated female patients, aged 6 months and 10 years,

presented with severe failure to thrive, developmental delay, andphysical features consistent with those seen in the Smith-Lemli-Opitz syndrome. Plasma cholesterol concentrations in both subjectswere very low (8-1 and 22 mg/dL [0209 and 0569 mmol/L],respectively). In addition, two other major plasma sterols weredetected: 7-dehydrocholesterol, 18 and 14mg/dL, respectively, andanother sterol (14 and 9-4 mg/dL) tentatively identified as

5a-cholest-6,8(9)-dien-3(3-ol.s Cholesterol accounted for only 9%of the total faecal neutral sterols from the younger girl, 7-

dehydrocholesterol and related compounds made up 49% ofdietary plant sterols constituted the remainder. Remarkably, thefaeces contained, at best, trace quantities of bile acids.

7-dehydrocholesterol is the penultimate sterol in the Kandutsch-Russell cholesterol biosynthetic pathway.6 Abnormally low plasmacholesterol concentrations and fetal excretion suggest deficientcholesterol synthesis. Accumulation of 7-dehydrocholesterol pointsto the enzyme that reduces the C-7,8 double bond of thisintermediate as the likely culprit. The inability of patients tosynthesise sufficient cholesterol may be the cause of the virtualdisappearance of bile acids and the reduced myelination seen in thisdisease.

Division of Clinical Genetics,Department of Pediatrics,New England Medical Center,Tufts University School of Medicine,Boston, Massachusetts 02111, USA

MIRA IRONSELLEN ROY ELIAS

Research Service,Department of Veterans Affairs,Medical Center,East Orange, New Jersey,and Department of Meeicine,

University of Medicine and Dentistryof New Jersey-New Jersey Medical School,

Newark, Jersey

GERALD SALENG. S. TINTASHOK K. BATTA

1. Smith DW, Lemli L, Opitz JM. A newly recognised syndrome of multiple congenitalabnormalities. J Pediatr 1964; 64; 210.

2. Fierro M, Martinez AJ, Harbison JW, Hay SH. Smith-Lemli-Opitz syndrome:neuropathological and opththalmological observatins. Dev Med Child Neurol 1977;19: 57.

3. Gorlin RJ, Cohen MM Jr, Levin LS. Smith-Lemli-Opitz syndromes. In: Gorlin RJ,Cohen MM Jr, Levin LS, eds. Syndromes of the head and neck. 3rd ed. New York:Oxford University Press, 1990: 890-95.

4. Pober B. Smith-Lemli-Opilz syndrome. In: Buyse ML, ed. Birth defects

encyclopedia. Cambridge, MA: Blackwell, 1990: 1570-72.5. Aexlson M. Occurrence of isomeric dehydrocholesterols in human plasma. J Lipid Res

1991; 32: 1441.6. Kandutch AA, Russell AE. Preputial gland tumor sterols III: a metabolic path from

lanosterol to cholesterol. J Biol Chem 1960; 235: 2256.

Giant platelets in erucic acid therapy foradrenoleukodystrophy

SiR,—Adrenoleukodystrophy (ALD) is an X-linked disorderthat results in the accumulation of saturated very-long-chain fattyacids, particularly hexacosanoic acid (26:0). The main clinicalphenotypes are a rapidly progressive infantile encephalopathy andadult myelo(neuro)pathy, both of which are frequently associatedwith adrenal insufficiency.’ The accumulation of 26:0 is

significantly reduced or normalised by administration of high dosesof erucic (22:1) and oleic (18:1) acid2 as a 4:1 mixture (Lorenzo’s oil)of glyceroltrioleate (GTO) and glyceroltrierucate (GTE). Despiteincomplete evaluation of clinical efficacy, but in the absence ofalternatives, this therapy is used in an increasing number of ALDpatients. Thrombocytopenia is a frequently observed side-effect,3and cardiotoxic effects of erucic acid have been subject to numerousinvestigations in past decades. To our knowledge, the influence oferucic acid on cellular haemostasis has not been reported.We report four patients aged between 10 and 40 years with ALD

who have been on a low fat diet (15% of total calorie intake) andGTO/GTE (20% of total calorie intake; GTE: z 15 g/kg) for morethan 6 months. Oils rich in polyunsaturated fatty acids (5 % of total