Alpha-mannosidosis: first symptoms in ten cases.

Nato Vashakmadze ^1,2 Natalia Zhurkova ² Marina Babaykina ² Ekaterina Vorontsova ¹ Natalia Aleshenko ² Gaziz Tufatulin ^3,4 Ekaterina Zakharova ⁵ Ludmila Mikhaylova ²

¹Pirogov Russian National Research Medical University., Russia
²Research Institute of Pediatrics and Children's Health in Petrovsky National Research Centre of Surgery., Russia
³Center of Pediatric Audiology, North-Western State Medical University named after I.I.-Mechnikov, Russia
⁴Saint-Petersburg Research Institute of Ear, Throat, Nose and Speech, Russia
⁵Research Centre for Medical Genetics, Russia

Background: Alpha-mannosidosis is a very rare lysosomal storage disease caused by mutations in the MAN2B1 gene that lead to a deficiency in alpha-mannosidase.
Methods: We followed ten patients with alpha-mannosidosis aged 2 to 30 years. Eight patients had their first symptoms at 12 months of age and two at 12-24 months of age. The median age at diagnosis of alpha-mannosidosis was 6.95 years [1,5;29]. A pathogenic nucleotide variant с.2248С>Т (p.Arg750Trp, NM_000528.3) was detected in homozygous state in six cases and in compound heterozygous state with a rare mutation in the MAN2B1 gene in four cases.
Results: Developmental delay, recurrent infections, otitis, adenoiditis, sensorineural deafness, macrocephaly, coarse face and dysostosis multiplex were observed in all cases. Hepatosplenomegaly was found in six patients, ataxia in four patients, congenital cataract in four patients, inguinal hernia in three patients and craniostenosis in one patient. In one case, early mental regression was diagnosed after 12 months, along with ataxia and kyphosis. This patient had a pathogenic nucleotide variant с.2248С>Т (p.Arg750Trp, NM_000528.3) in the MAN2B1 gene in compound heterozygous state with deletion c.2126_2127delAC (p.His709fs). In 5 cases, patients underwent surgical interventions prior to diagnosis. Non-syndromic hearing loss, mucopolysaccharidosis, Stickler syndrome and Marshall syndrome were ruled out in all patients before the diagnosis of alpha-mannosidosis.
Conclusion: Sensorineural deafness, recurrent infections, developmental delay, macrocephaly and dysostosis multiplex were the first alpha-mannosidosis symptoms in our patient group. Notably, congenital cataract was observed to be a common symptom in alpha-mannosidosis patients.