Juvenile Sulfatidosis Syndrome

At a glance

It is a very rare inborn error of metabolism combining the characteristics of metachromatic leukodystrophy and mucopolysaccharidosis. Lysosomal storage disease results from a lack of conversion (most likely in the endoplasmic reticulum) of cysteine into formylglycine. It is characterized by muscle weakness with spasticity, poor swallowing, recurrent pulmonary aspiration, and quadriplegia. Blindness and seizures due to hydrocephalus develop, eventually leading to death by the second decade of life. Aortic insufficiency and cervical cord compression have been reported.

Synonyms

Austin Disease; Mucosulfatidosis; Multiple Sulfatase Deficiency.

Incidence

It is believed that Juvenile Sulfatidosis Austin Type affects less than 200,000 people in the US population.

Genetic inheritance

Autosomal recessive.

Pathophysiology

The disease results from deficiency of at least seven different sulfatases, including arylsulfatase A, B, and C, iduronate 2-sulfate sulfatase, heparan N-sulfatase, N-acetylgalactosamine 6-sulfate sulfatase, and N-acetylglucosamine 6-sulfate sulfatase. This leads to the accumulation of a variety of sulfated compounds, including certain mucopolysaccharides, steroids, and sphingolipids. Evidence indicates the defect is a result of a disruption of the posttranslational process common to all the sulfatase enzymes, rendering them inactive.

Diagnosis

Clinical features and confirmatory laboratory results. Urinary excretion of total or individual sulfatides and glycosaminoglycans is increased. Serum and leukocytic sulfatase activity is reduced or absent. Neutrophils may show abnormal granulation. Cultured fibroblast sulfatase activity is reduced with abnormal sulfate incorporation kinetics. Cerebral fluid protein concentration is increased. Metachromic degeneration may be demonstrated in peripheral and central nerve tissue as a consequence of the accumulation of galactosphingosulfatides. Radiologic evidence of dysostosis multiplex may be present: broad ribs; narrow radial and ulnar shafts with wide and irregular metaphysis; small carpal bones; short and wide metatarsal and terminal phalanges of the great toes.

Clinical aspects

The clinical phenotypes combine the milder features of late infantile metachromic leukodystrophy and of mucopolysaccharidosis. Typically, patients have an initial period of normal development followed by the onset of motor and mental difficulty during the first or second year of life. In the later stage, most patients have developmental delay, coarse facial features (“gargoylism”), ichthyosis, hepatosplenomegaly, and skeletal abnormalities. Neurologic deterioration usually is rapid. Other reported features include seizure, deafness, hydrocephalus, chondrodysplasia calcificans, and abnormal fold of tissue between laryngeal and esophageal inlet in one case. Hemophagocytic Syndrome of fever, pancytopenia, coagulopathy, liver dysfunction, and proliferation of mature histiocytes was reported in one patient.

Precautions before anesthesia

Evaluate extent of demyelination, evidence of cord compression, and bulbar palsy. Mouth opening should be checked in case of temporal mandibular ankylosis. Electrolytes and coagulation profiles must be obtained. Urine sample must be obtained to exclude an associated mucopolysaccharidosis. An electrocardiogram (ECG) and echocardiogram must be ...