SERUM CHOLINESTERASE ANENZYMIA Report of a Case Confirmed by Enzyme‐histochemical Examination of Liver‐Biopsy Specimen

Abstract

SUMMARYA report is given on a 76‐year‐old woman who suffered from apnoea for 9 hours after administration of 40 mg succinyldicholine chloride. Serological examinations showed normal protein fractions, normal acetylcholinesterase (specific ChE) activity and complete absence of SChE (non‐specific ChE) activity. Enzyme‐histochemical examinations of a liver‐biopsy specimen also failed to reveal any activity. ChE could not be detected with butyryl thiocholine or acetyl thiocholine as substrates, whereas non‐specific esterases reacted entirely normal. There was no correlation between liver function (especially albumin synthesis) and ChE activity in this case of anenzymia. The fatty infiltration of the liver is discussed as an effect of the ChE anenzymia. It became evident that even complete absence of SChE may occur without any symptoms of illness or any serious disturbances in the serum proteins. The use of depolarising relaxants and of certain other esters (as is known in the case of atypical ChE) may, however, lead to serious complications.ZUSAMMENFASSUNGEs wird über eine 76‐jährige Patientin berichtet, bei der nach 40 mg Succinylbischolinchlorid eine 9‐stündige Apnoe auftrat.Die serologischen Untersuchungen ergaben normale Eiweissfraktionen, eine normale Acetylcholinesterase‐ (spezifische ChE) und ein vollständiges Fehlen der Serumcholinesteraseaktivität (unspezifische ChE). Die enzymhistochemischen Untersuchungen nach Leberbiopsie liessen ebenfalls keinerlei Aktivität erkennen. Weder mit Butyryl‐ noch mit Acetylthiocholin als Substrat gelang ein Cholinesterasenachweis, wohingegen unspezifische Esterasen völlig normal reagierten. Das gleichsiimige Verhalten von Leberfunktion (besonders Albuminsynthese) und ChE‐Aktivität ist bei der Anenzymie nicht zu finden. Die festgestellte Leberverfettung wird als Folge der Anenzymie der ChE diskutiert.Es zeigte sich, dass auch bei völligem Fehlen der Serumcholinesterase keine manifesten Krankheitssymptome auftreten, dass aber (wie von der atypischen ChE bekannt) nach Anwendung depolarisierender Relaxantien und bestimmter anderer Ester lebensgefährliche Komplikationen auftreten können.

Complete Pseudocholinesterase Deficiency: Genetic and Immunologic Characterization*

“…None of these bands was demonstrable in the sera of the two subjects homozygous for the "silent" gene. Three additional zones of esterase activity, previously described by Uriel (19) and Harris and his coworkers (16) (12). Since that organ is the site of pseudocholinesterase production, the total lack of enzyme in individuals homozygous for the silent allele is confirmed.…”

Pharmacokinetic and Pharmacodynamic Variability: A Daunting Challenge in Drug Therapy

“…In addition to succinylcholine, a prolonged duration of action was also observed for other ester drugs in patients who had atypical BChE. For example, procaine applied to a patient with low BChE activity had a prolonged effect lasting more than 160 min, compared to the normal 25 min [18]. Chloroprocaine injected for epidural anesthesia had an abnormally long duration of approximately 3 hr in a patient with atypical BChE, compared to the normal 45 min [19].…”

“…The K variant is the most common variant at a frequency of 1%. On the other hand, the A, S and F variants occur in homozygous form in 1 out of 3500, 100,000 and 150,000 Caucasians, respectively [18,20,21]. Despite the relatively high frequency of the K variant, the most frequently found variant in patients who respond abnormally to succinylcholine is the A variant.…”

“…Among these, at least 19 alleles are known to be not functional [55]. Some of them have single base pair mutations or small insertions/deletions leading to prematurely terminated protein products (CYP2D6 *3, *4, *6, *8, *11, *15, *19, *20, *38, *40, *42 and *44), while some allelic variants (CYP2D6*7, *12, *14 and * 18) produce proteins that are not functional. In addition, at least three alleles are the result of large chromosomal deletions (CYP2D6*5, *13 and *16).…”

Evidence for mutation being the source of the abnormal gene for plasma cholinesterase

“…Several other cases have since appeared in the literature (Doenicke et al, 1963;Szeinberg et al, 1966;Heyworth and Firth, 1967). These patients are believed to be homozygous for the so-called 'silent gene' but evidence is at present equivocal as to whether there is a complete failure of enzyme synthesis, or whether enzyme is present, but in an inactive form (Goedde, Gehring, and Hofmann, 1965;Hodgkin et al, 1965).…”