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
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
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
Succinylcholine should be avoided in
the presence of cervical and thoracic spinal cord compression. Avoid drugs
that rely entirely on hepatic metabolism in ...