Metachromatic leucodystrophy: a newly identified mutation in arylsulphatase A, D281Y, found as a compound heterozygote with I179L in an adult onset case

Late-onset metachromatic leukodystrophy

“…In one patient, I179S was associated with D281Y, which has never been observed at the homozygous state or in any other combination than with I179S and thus cannot be categorized as a 0-or R-type mutation. 10 In three patients, the I179S allele was associated with P426L, a well-known R-type allele.…”

“…Among these, two different clinical presentations have been observed: patients with progressive motor or sensory deficits and, on the other hand, cases with mental disturbance. [3][4][5][6][7][8][9][10][11][12] It has been suggested that these differences may originate from different specific mutations. 1,7,12 To explore a possible genotype-phenotype correlation in late-onset MLD on the basis of specific mutations, we studied the molecular and clinical data of 22 patients homozygous for mutation P426L and of 20 patients heterozygous for mutation I179S.…”

“…In the I179S patients, the second mutation was also characterized. Twenty-one unpublished and 21 reported patients [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22] fulfilled these criteria and were included (22 P426L homozygotes and 20 I179S compound heterozygotes) (see tables E-1 and E-2 on the Neurology Web site; go to www.neurology.org). In all patients, diagnosis of MLD was verified biochemically by determination of ASA activity in leukocytes or fibroblasts, sulfatide excretion in urine, or neuropathologic examination of nerve biopsy.…”

Adult metachromatic leukodystrophy: a new mutation in the schizophrenia-like phenotype with early neurological signs

“…The number of mutations found so far in adult MLD patients is quite limited. Beside a common missense mutation, P426L, predominantly found in patients with motor disturbances, another missense mutation, I179S, was found in adult MLD patients (Tylki-Szymanska et al, 1996;Halsall et al, 1999;Baumann et al, 2002).…”

“…Whereas Gieselmann et al (1994) showed that most adult motor forms of MLD present with a specific homozygous missense mutation, P426L, Baumann et al (2002) and others (Tylki-Szymanska et al, 1996;Halsall et al, 1999) reported on patients with the psycho-cognitive form, who were heterozygous for a specific mutation, I179S, together with an allele found in infantile cases. Recently, a homozygous patient with a novel mutation, F219V, a woman with progressive psycho-cognitive impairment without clinical or electrophysiological signs of peripheral nerve involvement, has been described (Maracao et al, 2005).…”