Non‐progressive psychomotor retardation in a child with severe deficiency of arylsulphatase A activity

Abstract

Severe deficiency of arylsulphatase A (ARSA) activity was detected in a boy with delayed psychomotor development, coarse face and liver enlargement when he was aged 2. The case does not fit into the description of the Metachromatic leukodystrophy (MLD) proposed by Hagberg (1963) mainly because he did not deteriorate. Twelve years of follow up did not show any signs of decerebration or further intellectual decline; only speech was, and still is, absent.The reduced ARSA activity in leukocytes and fibroblasts of the father of the propositus suggests that he is heterozygote and that the ARSA deficiency of the propositus is inherited. The ARSA activity of the mother overlaps with the lowest control. The assumption that the mother is a carrier of different mutations could explain the discrepancy between the clinical and biochemical findings of the patient. This is a further family in which mutations other than the typical one can be postulated to explain variable clinical or biochemical pictures of MLD.

Extremely low arylsulfatase A enzyme activity does not necessarily cause symptoms: A long‐term follow‐up and review of the literature

“…Moreover, in sporadic case reports on patients with undefined neuropediatric or neurometabolic disorders, the low ARSA activity was most likely coincidental and the reported clinical features were clearly different from MLD‐like disease features 40,41 . The controversy was fuelled by a case report on a patient with encephalitis disseminata , who was found to be compound heterozygous for a PD allele and a disease‐causing variant in the ARSA gene ( ARSA PD / ARSA − ) 23 .…”

“…Moreover, in sporadic case reports on patients with undefined neuropediatric or neurometabolic disorders, the low ARSA activity was most likely coincidental and the reported clinical features were clearly different from MLD‐like disease features. 40 , 41 The controversy was fuelled by a case report on a patient with encephalitis disseminata , who was found to be compound heterozygous for a PD allele and a disease‐causing variant in the ARSA gene ( ARSA PD / ARSA − ). 23 Although the authors suggest that low ARSA activity might have caused a long‐term accumulation of sulfatides and thus facilitated the demyelinating process and neuropsychiatric symptoms, up to date, no further pathophysiological, neuroradiological or statistical evidence supports this hypothesis.…”

Diagnosis of arylsulfatase A deficiency in intact cultured cells using a fluorescent derivative of cerebroside sulfate

“…The sulfatide "loading test" in cultured cells is at present the most reliable and unambiguous technique for defining the two respective conditions of ASA deficiency, namely MLD and PD which are indis- individual. This test also permits a discrimination between "true" MLD patients and "atypical" variant patients with low ASA activity who are in fact PD homozygotes and whose clinical manifestations are unrelated to the ASA deficiency (Butterworth et al 1978, Danesino et al 1984, Finelli 1985, Manowitz et al 1981, Nordenbo & Tsnnesen 1985. These problems occur frequently because of the relatively high frequency of the PD allele.…”