Anesthetic Management of a Boy with Congenital Disorder of Glycosylation (CDG) I-x

doi:10.4236/ijcm.2011.23056

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International Journal of Clinical Medicine, 2011, 2, 325-327

doi:10.4236/ijcm.2011.23056 Published Online July 2011 (http://www.SciRP.org/journal/ijcm)

325

Anesthetic Management of a Boy with Congenital

Disorder of Glycosylation (CDG) I-x

Amit Lehavi1,3*, Hanna Mandel2,3,4 , Yeshayahu (Shai) Katz1,3,4

1Department of Anesthesiology, Rambam Healthcare Campus, Haifa, Israel; 2Metabolic Unit, Meyer Children’s Hospital, Haifa,

Israel; 3Rambam Health Care Campus, Haifa, Israel; 4Bruce Rappaport Faculty of Medicine, Technion (Israel Institute of Technol-

ogy), Haifa, Israel.

Email: *[email protected]

Received April 16th, 2011; revised April 27th, 2011; accepted May 27th, 2011.

ABSTRACT

Congenital di sorders of glycosylation (CDGs) are g roup group of g enetic defects in the assembly and processing path-

way of protein glycosylation, which cause a wide range of multi system dysfunction. This paper describes the anesth etic

management of 6 years old boy with CDG type I-x for upper airway surgery. We used a sevoflurane-nitrous ox-

ide-remifentanil regime with no complications and good results. As for now, the literature lacks reports of anesthetic

management of children with CDG I-x, and this report may provide clinicians an option for safe anesthetic manage-

ment.

Keywords: Anesthesia, Pediatric, Metabolic Disorders, Congenital Disorders of Glycosylation, CDG

1. Introduction

Congenital disorders of glycosylation (CDGs) are group

of genetic defects in the assembly and processing path-

way of protein glycosylation. This causes a phenotype of

which growth, cardiac, neurological, hematological,

gastrointestinal, renal, and dermatological and ophthal-

mological systems are affected in various penetration.

The literature concerning information on the anesthetic

management of CDG patients is very limited. The pur-

pose of our report is to raise the awareness of anesthesi-

ologists to this group of disorders, with emphasis on the

CDG I-x subtype, because specific diagnosis of any en-

tity is important for preventive measures. We describe

the anesthetic management of a six years old boy suf-

fering from CDG Type I-x, which was referred for an

upper airway surgery under general anesthesia.

2. Case Presentation

DS is a 6 years old boy, whose parents are second degree

cousins of Druze origin. He was considered as a healthy

and normally developing boy until his brother was found

to have hypertransaminasemia and dilated cardio-

myopathy. These findings led to the screening of all

family members including DS who was found to have

the same symptoms as his brother including hypertrna-

saminasemia and dilated cardiomyopahty at the age of 5

years. The boy, weighing 16.2 kg (second per-

centile), had no cognitive impairment, and physical ex-

amination did not reveal any abnormal findings. He was

put on oral captopril 2.5 mg twice daily. Retrospectively,

his medical chart showed a constant finding of hyper-

transaminasemia since the age of 6 months with alanine

aminotransferase, (ALT) up to 387 U/L (normal values:

5 - 45 U/L) and aspartate aminotransferase (AST) rising to

302 U/L (normal values: 15 - 55 U/L). Serum bili- rubin,

alkaline phosphatase and gammaglutamyltrans-peptidase

(GGT) were normal, as were total protein, albumin, cho-

lesterol, iron, ferritin, blood count, creatine phosphokinase,

electrolytes, urea and creatinine. Further metabolic studies

including serum lactate, aminoacids and urinary organic

acids were normal. Isoelectric focusing of transferrin

was performed because CDGs are considered in the dif-

ferential diagnosis of hypertransaminasemia and dilated

cardiomyopathy. Serum isoelectrofocusing (IEF) of

transferrin revealed a type I profile suggesting a glycan

assembly defect (CDG-I). However, analysis of the pa-

tient’s fibroblasts eliminated the possibility of CDG I-a

and CDG I-b; lipid-linked oligosaccharide analysis did

not show any abnormal accumulation of glycan interme-

diates. To date, the primary genetic defect of the glyco-

sylation pathway remains unknown, thus we designated

the siblings’ disorder as CDG I-x.

Anesthetic Management of a Boy with Congenital Disorder of Glycosylation (CDG) I-x

326

The child was scheduled for tonsillectomy and adenoi-

dectomy due to upper airway obstruction. Coagulation

studies revealed decreased levels of Protein C, Protein S

and Factor XI (26%, 59% and 45% respectively), with

normal prothrombin (international normalized ratio 1.26)

and partial thromboplastin time 25 sec.

3. Anesthetic Management

The child was instructed to fast the evening prior to sur-

gery, and did not receive oral premedication. Induction

of anesthesia was achieved with a mixture of 50% O2

and 50% N2O under spontaneous breathing, and se-

voflurane added step wisely up to 5% until uncon-

sciousness was gained. A 25 G intravenous line was

inserted to a superficial vein in the forearm, and after

administration of atropine 0.1 mg (≈6 mg/kg), infusion

of remifentanil was started at a rate of 0.5 mcg/kg/min.

A bolus dose of atracurium 10 mg (≈6 mg/kg) was given

and the boy was ventilated with a facemask for three

minutes with 100% O2. Direct laryngoscopy with #1

Macintosh blade enabled good view of the vocal cords

(Cormack score 1) and endotracheal intubation with an

uncuffed 5 mm internal diameter endotracheal tube was

facilitated.

After fixation of the endotracheal tube the eyes were

taped, a wire thermometer was inserted in the rectum

and the boy was wrapped with an air heated blanket

connected to a forced air warmer set at 38˚C. A bolus

dose of 1 mg morphine (≈60 mcg/kg) was injected and

the sevoflurane concentration was lowered to 0.3 in the

expired air.

The operation lasted 50 minutes, during which there

was no significant bleeding; the heart rate was stable at

80 beat/min and blood pressure at 90/60 mmHg.

At the end of the procedure the remifentanil infusion

was stopped, sevoflurane withhold and the boy was ven-

tilated with 100% O2 for 5 min. Atropine 0.2 mg and

neostygmine 0.5 mg were given to prevent residual

neuromuscular blockade. Four min later the boy gained

consciousness and began to breathe spontaneously. The

trachea was extubated and the boy was taken to the post

anesthesia care unit (PACU).

During 70 minutes of PACU stay the boy was stable,

did not experience events of desaturation, hypotension,

nausea or vomiting. He was given two more doses of 1

mg morphine for analgesia, and discharged to the pedi-

atric surgery department with Aldrete score 4.

During the next day in the pediatric surgery depart-

ment he gradually started ingesting soft food, and was sent

home 24 hours later with no signs of bleeding.

4. Discussion

As for now, the literature lacks reports of anesthetic

management of children with CDG I-x, and this report

may provide clinicians an option for safe anesthetic

management. The use of propofol based anesthesia, as

well as the use of longer acting muscle relaxants and

opioides may result in prolonged eduction and undesir-

able adverse reactions.

CDGs, formerly known as carbohydrate-deficient gly-

colprotein syndromes, consist of at least 18 genetic de-

fects in the glycosylation of proteins. The CDGs com-

prise two groups. The first group, CDG I, includes de-

fects in the N-glycan assembly localized in the cytosol

and the endoplasmic reticulum (ER) including type I-a to

I-l; CDG II comprises disorders in the processing of gly-

coproteins in the ER and Golgi apparatus accounting for

types II-a to II-f [1]. Untyped cases are labeled CDG-x

until the gene and its protein will be identified [2]. IEF of

serum transferrin remains the most powerful screening

test for CDG, although not all types can be detected by

this assay. A type I IEF pattern (observed in CDG I) is

characterized by a decrease of tetrasialotranferrin and an

increase of di- and asialotransferrin bands, whereas a

type 2 pattern (observed in CDG II) shows in addition

and increase of tri- and monosialotransferrin [3].

The reports of various types have emphasized marked

phenotypical variability of this multisystemic group of

disorders [4]. The clinical presentation of CDG may

include growth retardation, short limbs, delayed puberty

and hypogonadism; hypertrophic or dilated cardiomyo-

pathy and pericarditis [5] ataxia, psychomotor retarda-

tion, epilepsy, hypotonia, cerebral and cerebellar atrophy;

bleeding tendency due to a decrease in Factors VII lev-

els, and/or thromobosis due to decreased clotting factor

XI, protein S and protein C; liver fibrosis and cirrhosis,

chronic diarrhea, vomiting and protein-losing enteropa-

thy; nephrotic syndrome; ichthyosis, abnormal fat pads

and inverted nipples; and strabismus, abnormal eye

movements, optic nerve atrophy, coloboma and retinitis

pigmentosa.

IEF of serum transferring remains the most powerful

screening test for CDG, although not all types can be

detected by this assay. A type I IEF pattern (observed in

CDG I) is characterized by a decrease of tetrasialotran-

ferrin and an increase of di- and asialotransferrin bands,

whereas a type II pattern (observed in CDG II) shows in

addition and increase of tri- and monosialotransferrin.

This case report presents a possible anesthesia regi-

men to be used in patients with CDG Ix scheduled for

surgery. Previous report [6] regarding anesthetic man-

agement of CDG I patient described a sevoflurane-pro-

pofol-sufentanyl based regimen. Since propofol tends to

lower systolic blood pressure and cardiac output, it pos-

ses a potentially negative effect in hemodynamiclly un-

stable patients and in patients with severe structural

Anesthetic Management of a Boy with Congenital Disorder of Glycosylation (CDG) I-x

327

heart disease or congestive heart failure. Cardiac in-

volvement contributes significantly to morbidity and

mortality and probably to sudden death in CDG patients,

thus propofol may better be circumvented in these pa-

tients.

The use of remifentanil is proven to reduce postopera-

tive nausea and vomiting [7] and to provide faster re-

covery and shorter time to tracheal extubation compared

with fentanyl or sufentanyl in tonsillectomy and ade-

noidectomy in the pediatric population [8]. Since re-

mifentanil is metabolized by non specific esterases [9],

its metabolism could be less affected by hepatic dys-

function resulting from CDG. We believe the use of a

nitrous oxide-remifentanil based anesthesia regimen may

be preferred for CDG I-x patients requiring general an-

esthesia.

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