Juvenile Sulfatidosis Syndrome

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

Austin Disease; Mucosulfatidosis; Multiple Sulfatase Deficiency.

Autosomal recessive.

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.

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.

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.

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 to exclude associated mucopolysaccharidosis. An electrocardiogram (ECG) and echocardiogram must be obtained if a cardiac lesion is suspected.

Potential for airway difficulty with abnormal facial features and airway anomalies, despite the lack of mention of poor mouth opening or poor neck extension in any report. Poor cooperation because of mental retardation. Severe neurologic deterioration may predispose to lungs aspiration. Care in positioning of patients presenting with limited joint mobility.

Succinylcholine should be avoided in the presence of cervical and thoracic spinal cord compression. Avoid drugs that rely entirely on hepatic metabolism in cases of hepatic dysfunction. Meperidine, ketamine, and enflurane are relative contraindications if seizures are present.

Metachromic Leukodystrophy: Lysosomal storage disease caused by defective lysosomal arylsulfatase, resulting in progressive loss of white matter in the nervous system with gait disturbance, mental regression, and urinary incontinence. Gene map locus is 22q13.31-qter.

Mucopolysaccharidoses (MPS): Group of inherited metabolic storage disease caused by various defective lysosomal enzymes with progressive multiorgan degeneration.