Sly syndrome

(Mucopolysaccharidosis type VII)

Autosomal recessive transmission of a mutation of one of the GUSB genes (7q11.21) which causes beta-D-glucuronidase deficiency, leading to accumulation of several glycosaminoglycans (dermatan sulfate (DS), heparan sulfate (HS) and chondroitin sulfate (CS)) in lysosomes. The disease is expressed in homozygous or heterozygous composite patients.

The phenotype is highly variable:

- prenatal forms with non-immunological feto-placental hydrops,

- severe neonatal forms with facial dysmorphism (coarse features), short neck, hernias, hepatosplenomegaly, clubfoot, dysostosis, joint retractions, short stature and severe hypotonia, as well as neurological involvement leading to profound intellectual disability in patients who survive. Pulmonary involvement and cardiac valvulopathy. Corneal opacities.

- very mild cases, identified in adolescence or adulthood following the onset of thoracic kyphosis.

Substitutive treatment with recombinant human beta-glucuronidase has been approved in Europe and the United States: its efficacy in improving gait, lung function and hepatosplenomegaly has been demonstrated. In late-onset forms, treatment is mainly orthopedic.

Anesthetic implications:

Difficult intubation.

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 of the cervical spine	non limited 60-90° flexion 30-60° flexion < 30° or instable	0 1 2 3
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 4	0 1 2 3
6	Thyromental distance	> 6 cm 5-6 4-5 < 4	0 1 2 3
7	larynx height - epiglottis/ soft palate	> 4 cm 3-4 2-3 < 2	0 1 2 3
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 1 2 3
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 2 3
10	glottis bulkiness	normal (filling < 1/3 of the glottis) mild (1/3 to ½ ) moderate (1/2 ) severe (filling the entire glottis)	0 1 2 3
11	sub-glottis or cricoid diameter	> 7 mm 6-7 5-6 > 5	0 1 2 3
12	tracheomalacia or tracheal stenosis	no stenosis decrease of 50-75 % decrease of 75-99 % complete obstruction	0 1 2 3
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

References :

- Toda Y, Takeuchi M, Morita K, Iwasaki T, Oe K, Yokoyama M, Hirakawa M.
Complete heart block during anesthetic management in a patient with mucopolysaccharidosis type VII.
Anesthesiology 2001; 95: 1035-7.

- 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