Neuraminidase Deficiency

Alternative Names

  • Sialidosis, Type II
  • Mucolipidosis I
  • ML I
  • Lipomucopolysaccharidosis
  • Sialidase Deficiency
  • Glycoprotein Neuraminidase Deficiency
  • NEUG Deficiency
  • Neuraminidase 1 Deficiency
  • NEU Deficiency
  • NEU1 Deficiency
  • Sialidosis, Type I
  • Cherry Red Spot-Myoclonus Syndrome
  • Myoclonus-Cherry Red Spot Syndrome
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WHO-ICD-10 version:2010

Endocrine, nutritional and metabolic diseases

Metabolic disorders

OMIM Number

256550

Mode of Inheritance

Autosomal recessive

Gene Map Locus

6p21.3

Description

Neuraminidase deficiency, commonly known as sialidosis, is a lysosomal storage disorder, characterized by a deficiency of the enzyme alpha-N-acetyl neuraminidase (sialidase). Sialidosis is classified into two main forms based on the phenotypic features. Type I sialidosis is typified by symptoms of myclonic epilepsy, visual problems, ataxia, and most characteristically, the presence of macular cherry red spots in the second or third decade of their life. This form of the disease is often referred to as cherry red spot-myoclonus syndrome. Sialidosis type II is a more severe form of the disease, typically present with an earlier onset of disease. In fact, type II sialidosis can present in a congenital or an infantile form; both proving fatal before the third year of life. The most severe form of the disease occurs in utero, resulting in still birth or death within a few months after birth. Typical symptoms of sialidosis in infants include flat nasal bridge, puffy eyelids, enlargement of the gums and tongue, and occasionally skeletal malformations. Older children may show tremors, impaired vision, seizures, hypotonia, and mental retardation.

No cure is available for sialidosis. Treatment is aimed at the clinical features presented. Seizures are difficult to control with anti-convulsant medications. The myoclonus often interferes with walking.

Molecular Genetics

Sialidosis is an autosomal recessive disorder resulting from defects in the lysosomal from of the sialidase enzyme (alpha-N-acetyl neuraminidase), which catalyzes the removal of sialic acid moieties from glycoproteins and glycolipids. Loss of function of this enzyme results in excess sialyl-oligosaccharides accumulating in the cells and causing damage. This accumulation can be observed histologically in the form of abnormal vacuolization of the cells, especially cells of the CNS, skeletal system, and the reticuloendothelial system.

Epidemiology in the Arab World

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Other Reports

Oman

Nair et al. (1999) (Oman Med J. 1999; 16(2):7-9) reported a neonate with sialidosis II who presented with hydrops fetalis. This baby girl was born to consanguineous parents after uneventful pregnancy during which the mother whose blood group was A Rh positive, did not have any antenatal ultrasound scan. The infant weighed 3.22 kg at birth and did not need any resuscitation. She had dysmorphic features which included coarse facies, generalized edema, hemangioma over both eyelids, and small petechia and erythematous rash over the upper trunk. The abdomen was distended with ascites and hepatomegaly (4 cm), which was confirmed by abdominal ultrasound. Ophthalmic examination revealed bilateral retinal hemorrhages with no cherry red spots. Other systemic examinations were normal with no cardiomegaly or murmurs heard. Investigations revealed normal Hb, elevated white cell count (15 x 10(power 9)/L), low platelets (80 x 10(power 9)/L), cytoplasmic vacuolation of lymphocytes, blood group A Rh positive, low serum albumin with no protinuria, normal hemoglobin electrophoresis, coagulation profile, liver enzymes, negative Coomb's test, negative serology for intrauterine infections (syphilis, parvovirus), and normal chromosomal analysis. Two-dimentional echocardiography revealed dilated left sided chambers with normal left ventricular systolic function, and the myometrium had shaggy appearance, but the chest X-ray (showed minimal pleural effusion) and ECG were normal. Plenty of vacuolated lymphocytes were detected on bone marrow examination, and on liver biopsy, there were hepatocytes with vacuolated cytoplasm and enlarged Kupffer cells with foamy cytoplasm, which contained Alcian blue positively stained material. Both parenchymal and Kupffer cells were PAS positive. This immunohistochemical staining confirmed the diagnosis of sialidosis II which was further supported by the intracellular detection of multiple large vacuoles with reticulogranular and lamellated material consistent with mucolipidosis with electron microscopy. The baby was managed in a special care baby unit where she was ventilated, as she developed respiratory distress at 12 hours of age. But she continued to deteriorate despite symptomatic and supportive measures, and died after 12 days from pseudomonas septicemia.

Joshi et al. (2002) carried out a retrospective analysis of all patients born with inborn errors of metabolism in Oman between June 1998 and December 2000. Among the 82 patients, only one was diagnosed with sialidosis [CTGA Database Editor's note: Computed annual incidence rate is 0.8/100,000].

Saudi Arabia

Gascon et al. (1992) reported a large, consanguineous Saudi family with three members with sialidosis type 1 and five members with infantile central nervous system spongy degeneration of the brain (ICNSSD, or Canavan-Bertrand-van Bogaert disease). Patients with sialidosis had normal aspartoacylase activity, while neuraminidase activity in the patients with ICNSSD was reduced. All patients had normal carboxypeptidase activity in their fibroblasts. In an additional member there was photic-induced epilepsy, but he had normal enzymes. Two of the patients and one normal brother, but not the parents, had pericentric inversion of chromosome 9q.

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