Progressive cerebellar ataxia in juvenile GM 2 -gangliosidosis type Sandhoff

Abstract

Sir: The classical infantile forms of Tay-Sachs and Sandho disease (GM 2 -gangliosidosis types B and 0) exhibit a relatively uniform clinical picture characterized by early neurological deterioration leading to a decerebrate, vegetative state by the 2nd to 4th year of life. Late-onset forms, however, present a wide spectrum of clinical manifestations with a predominant involvement of one part of the CNS.We observed an 8-year-old girl with Sandho disease in whom severe ataxia was the leading symptom. Intention tremor and gait diculties arose from the 1st year of life. Clinical evaluation at the age of 8 years revealed a very shy girl who exhibited an ataxic gait and diculty in standing alone without support. There was a marked action tremor and dysdiadochokinesis of the hands which interfered with precise movements. Tendon re¯exes of the lower extremities were brisk with positive Babinski sign. Cranial nerve functions were normal; nystagmus was not observed. Fundoscopy was normal with no cherry-red macular spot. The EEG showed normal electrical activity without spike discharges. The child could speak and draw simple ®gures, but was unable to write. Liver and spleen were not enlarged. Correlating with the clinical presentation MRI revealed a marked cerebellar atrophy, whereas images of the cerebral hemispheres and thalamus did not reveal any pathological change (Fig. 1).The progressive clinical course suggested a lysosomal storage disorder. Several lysosomal enzymes were determined in the patientÔs serum and ®broblasts using arti®cial¯uorogenic substrates according to standard methods. A profound de®ciency of total hexosaminidase was detected in both the patientÔs serum (1.3 0.2 nmol/min/ml; normal range 19.2±51.2, median 28.9 nmol/min/ml, n 40) and ®broblasts (5.4 0.6 nmol/min/ mg protein; normal range 125±300, median 228 nmol/min/mg protein, n 35). Hexosaminidase A activity, as determined with the sulphated¯uorogenic substrate was also de®cient. The reference enzyme (b-glucuronidase) activity was in the normal range.

GM2 gangliosidosis variant B1

“…Unfortunately, that study focused mainly on the neuropathological aspects of the disease, and no further MRI examinations were performed during the subsequent clinical course. [2]. The MRI data for patient 3 were peculiar insofar as no basal ganglia or thalamus involvement was observed, which conforms to the observations made of Beck's patient and in adult patients with GM2 gangliosidosis.…”

“…There have been few reports of the juvenile-or late-onset (or chronic) forms [2,9,15]. No data on GM2 gangliosidosis variant B1 are available in the literature.…”

Lysosomale Speicherkrankheiten

“…Oft liegt gleichzeitig eine leichte Demenz vor. Eine G M2 Gangliosidose kann sich auch als progressive zerebelläre Ataxie manifestieren[3].Die Behandlung der meisten lysosomalen Speicherkrankheiten beschränkt sich derzeit noch auf symptomatische Maßnahmen. Die Transplantation von allogenem Knochenmark ist nach aktuellem Wissenstand bei Morbus Hurler indiziert, wenn sie vor dem 2.…”