|
Hurler, disease or syndrome
|
(Mucopolysaccharidosis type I H, gargoylism)
Prevalence: 1/100.000. Autosomal recessive transmission of mutations in the IDUA gene (4p16.3).
Depending on the clinical presentation, there are
- severe form: Hurler (also known as 'with intellectual regression')
- moderate: Scheie syndrome
- intermediate form: Hurler-Scheie.
Clinical signs:
- coarse facies in infancy with typical aspect of the face ( "gargoyle" facies) from the age of 2-3 years: depression in the base of the nose, thick lips, wide and anteverted nostrils , macroglossia, thick skin, hirsutism with low implanted eyebrows.
- pharyngolaryngeal infiltration with chronic nasopharyngeal obstruction; increasing respiratory problems and obstructive apnea; seromucosal otitis
- hydrocephalus
- short neck with instability of C1 on C2; sometimes narrow spinal cervical canal with a risk of spinal cord compression
- low dorsal kyphosis
- skeletal abnormalities: 'dysostosis multiplex' with an osteomalacic aspect of the long bones: coxa valga, genu valgum. abnormalities of the vertebrae of D12 to L3 : anteroposterior hypoplasia ("hammer" deformity)
- arthropathy: progressive stiffness of the joints, flexion of elbows and knees, claw hands, carpal tunnel, tip-toe walking
- hepato-splenomegaly; sometimes chronic diarrhea
- corneal opacities.
- thickening of the mitral and aortic valves followed by a narrowing of the valvular surfaces; hypertrophic cardiomyopathy, coronary artery disease; sometimes pulmonary hypertension caused by chronic cor pulmonale
- small, stocky limbs, protruding abdomen (umbilical and inguinal hernias)
- deafness associated with frequent ear infections and a progressive involvement of the ossicles
Death between 7 and 15 years of age (by cardiac or respiratory failure).
Two treatments are available:
- bone marrow transplantation with bone marrow or stem cells; it causes a regression of visceral and respiratory impairment, and neuropsychological improvement if it is performed before the age of 2 years; it is less effective on orthopaedic aspects
- intravenous recombinant enzyme therapy is available (α-L-iduronidase: Elaprase®) at a dose of 100 to 200 IU/kg per week; it is effective on joint mobility, lung capacity and organomegaly but does only modify the cognitive, neurological, bone and heart defects if it is started before the age of 5 years; the long-term effectiveness is not yet known (emergence of antibodies against the recombinant enzyme);
At present, the two treatments are often associated.
Anesthetic implications:
difficult intubation, worsening with age except in case of bone marrow transplant therapy before the age of 2 years.
Obstructive apnea: use a nasopharyngeal rather than oral pharyngeal. Risk of cardiac complications (mitral or aortic valvular disease and coronary heart disease). Expect technical difficulties (vertebral anomalies) and increased risk for complications (narrow spinal canal) when planning an epidural block. Technique of intubation: inhalation induction, laryngeal mask and eventually use the laryngeal mask as a conduit for intubation with the fiberscope. There is still a risk of intubation failure. Emergence of anesthesia is dangerous: risk of obstruction of the airway and of low pressure pulmonary edema.
An airway assessment score has been developed for adolescent and adult (even treated) patients with mucopolysaccharidosis: the Salford score (table). It comprises 15 parameters graded from 0 to 3. Parameters 1-6 are based on clinical examination, 7-10 on nasal endoscopy, 11-13 on chest CT and 14-15 on respiratory function tests (if feasible).
A total score of 0-15 indicates minor, 15-30 moderate and 30-45 severe involvement of the airways. A score of ≥ 25 means that difficult airway management should be considered.
|
Nr |
parameter |
measures |
score |
|
1 |
mouth opening |
> 5 cm 4-5 3-4 < 3 |
0 1 2 3 |
|
2 |
teeth protrusion (profile) |
none minor moderate severe |
0 1 2 3 |
|
3 |
mobility /stability
|
non limited 60-90° flexion 30-60° flexion < 30° or instable |
0
|
|
4 |
tongue bulkiness |
normal light (< 1/3 of the floor) moderate (1/3 to ½ of the oral cavity) severe (> 1/2 of the oral cavity) |
0 1 2 3 |
|
5 |
Mallampati score |
1 2 3
|
0
|
|
6 |
Thyromental distance |
> 6 cm 5-6 4-5 < 4 |
0 1
|
|
7 |
larynx height - epiglottis/ soft palate |
> 4 cm 3-4 2-3 < 2 |
0
|
|
8 |
epiglottic bulkiness |
normal (filling < 1/3 of the oropharynx) mild (1/3 to ½ of the oropharynx) moderate (1/2 of the oropharynx) severe (filling the entire oropharynx) |
0
|
|
9 |
supra-glottis bulkiness |
normal (filling < 1/3 of the laryngopharynx) mild (1/3 to ½ ) moderate (1/2 ) severe (filling the entire laryngopharynx) |
0 1
|
|
10 |
glottis bulkiness |
normal (filling < 1/3 of the glottis) mild (1/3 to ½ ) moderate (1/2 ) severe (filling the entire glottis) |
0
|
|
11 |
sub-glottis or cricoid diameter |
> 7 mm 6-7 5-6 > 5 |
0
2 3 |
|
12 |
tracheomalacia
|
no stenosis decrease of 50-75 % decrease of 75-99 % complete obstruction |
0
|
|
13 |
Tracheal tortuosity |
none present |
0 3 |
|
14 |
Expiratory volume max 1 sec |
> 80 % 60-79 40-59 < 40 |
0 1 2 3 |
|
15 |
Vital capacity |
> 80 % 60-79 40-59 < 40 |
0 1 2 3 |
It is estimated that approximately 36% of children with Hurler Syndrome undergo anesthesia/surgery before the diagnosis is made: it is therefore important to know the phenotype of this condition in order to recognize it or to suspect it. The international register ISDM started in 2003 estimates post-surgical mortality within 30 days following surgery at about 0.7%, all types of surgeries being included, and this despite treatment with enzyme substitution or stem cell transplantation.
Given the risk of neurological complications even after surgery that does not involve the spine, it is useful to rely on the intraoperative monitoring of the evoked sensory and the motor potentials:
- in case of kyphosis > 60° and an estimated surgical duration of > 60 min
- in case of kyphosis < 60° and an estimated surgical duration of > 90 min
The basic values must be established with the patient supine and then in the position needed for surgery. Any change in amplitude > 50 % and/or increase in latency > 10 % of the evoked sensory potential, or any change in the polyphasic aspect of the evoked motor potentials must lead to a therapeutic reaction: check the BP, the depth of anesthesia, the hemoglobin level, the temperature, the position of the patient.
|
EXPERT CONSENSUS for MANAGEMENT:
Surgical morbi-mortality is higher than in the normal population and the risk of anesthetic complications is very high: these patients must therefore be managed in facilities where care of those complications can be taken. It is why : - a full neurological examination is necessary before general or locoregional anesthesia - imaging (MRI or CTscan) of the full spine is recommended - a flexion/extension MRI of the cervical spine is necessary if there is any concern about its stability - polysomnography, respiratory functional tests (restrictive or obstructive syndrome) and cardiac evaluation (echocardiography) must be considered before an anesthesia - morphological and functional anomalies of the upper airway, a decrease in mobility of the cervical spine and bronchial airway anomalies increase the morbidity and mortality of anesthesia - a sedative premedication can be administered before anesthesia - for intubation, a videolaryngoscope and a intubating fiberscope must be immediately available - tracheostomy can be extremely difficult in those patients, particularly in emergency; it is crucial to identify the position of the cricothyroid membrane (XRays, echography) before anesthesia - extubation must be preferably done in the operating room; if this may not be the case, an experienced team must be present - in patients in whom a fragility of the spinal cord is suspected (concept of spinal cord at risk : significant cyphosis, risk of hypotension, long lasting surgery, difficult surgical positioning), neurological monitoring must be done during the whole procedure, and it is better to avoid epidural anesthesia Reference:
|
References :
- Frawley G, Fuenzalida D, Donath S, Yaplito-Lee J, Peters H.
A retrospective audit of anesthetic techniques and complications in children with mucopolysaccharidoses.
Pediatr Anesth 2012; 22: 737-44.
- Megens JHAM, de Wit M, van Hasselt PM, Boelens JJ, van der Werff DBM, de Graaff JC.
Perioperative complications in patients diagnosed with mucopolysaccharidosis and the impact of enzyme replacement therapy followed by hematopoietic stem cell transplantation at early age.
Pediatr Anesth 2014; 24: 521-7.
- Kloesel B, Holzman RS.
Anesthetic management of patients with inborn errors of metabolism.
Anesth Analg 2017; 127: 822-36
- Dalesio MN, Ifaturoti OA, Tomeldan CM, Tran TP.
Airway anatomy of an adult with Hurler’s syndrome.
Anesthesiology 2020 ; 132 : 1557
- Kandil AI, Pettit CS, Berry LN, Busso VO, Raeskey M et al.
Tertiary pediatric academic institution’s experience with intraoperative neuromonitoring for nonspinal surgery in children with mucopolysaccharidosis based on a novel evidence-based care algorithm.
Anesth Analg 2020; 130: 1678-84.
- Gadepalli C, Stepien KM, Sharma R, Jovanovic A, Tol G, Bentley A.
Airway abnormalities in adult mucopolysaccharidosis and development of Salford mucopolysaccharidosis airway score.
J Clin Med 2021;10: 3275. doi.org/10.3390/jcm10153275
Updated: February 2024