The Differential Diagnosis of Adult Onset Metachromatic Leukodystrophy and Early Onset Familial Alzheimer Disease in an Alzheimer Clinic Population

Abstract

Clinical differentiation between forms of progressive dementia can prove difficult, particularly when relatively rare forms of dementia are involved. Factors such as family history of dementia, age at onset, presenting features such as personality change, cognitive deficits, psychiatric symptoms, and clinical course (progressive deterioration; retention of skills over time) may prove useful for directing investigations to identify underlying pathology and genetic implications. This is illustrated by two patient reports. Each patient had the onset of memory/behavioral problems at approximately age 40 years, was initially given a psychiatric, non-dementing diagnosis, and had a positive family history for early onset behavioral and memory problems. After longitudinal assessment, the diagnosis of Alzheimer disease was confirmed at autopsy in one patient and a diagnosis of familial, adult-onset metachromatic leukodystrophy in the other. RESUME: Diagnostic differentiel de la leucodystrophie metachromatique de I'adulte et de la maladie d'Alzheimer familiale dans une clinique d'Alzheimer. II peut etre difficile de differencier cliniquement les formes progressives de demence, particulierement quand il s'agit de formes relativement rares. Des facteurs comme une histoire familiale de demence, l'age de debut, les manifestations initiales, telles les changements de personnalite, les deficits cognitifs, les symptomes psychiatriques, et 1'evolution clinique (la deterioration progressive, la preservation a travers 1'evolution de certaines habiletes) peuvent s'averer utiles pour orienter l'investigation dans le but d'identifier la pathologie sous-jacente et les implications genetiques. Nous rapportons deux cas qui illustrent ce fait. Les problemes de memoire/de comportement ont commence vers l'age de 40 ans chez chacun des deux patients, tous les deux ont reiju un diagnostic psychiatrique ne comportant pas de demence et avaient une histoire familiale positive de problemes precoces de comportement et de memoire. A la suite d'une evaluation longitudinale, le diagnostic de maladie d'Alzheimer a ete confirme a l'autopsie chez un patient et un diagnostique de leucodystrophie metachromatique de I'adulte chez I'autre.

Isolated Peripheral Neuropathy in Atypical Metachromatic Leukodystrophy: A Recurrent Mutation

“…1 Psychiatric problems are the most common initial symptom and the disease may be mistaken for schizophrenia, Alzheimer's disease, or depression. [17][18][19][20] It has been observed that symptoms of peripheral neuropathy may not be obvious clinically although they will be evident on nerve conduction studies. 21,22 Isolated peripheral neuropathy associated with late onset MLD may be mistaken for Charcot-Marie-Tooth disease in the absence of EM studies and biochemical analyses.…”

Metachromatic Leukodystrophy – An Update

“…In the juvenile patients the onset of disease may not be dominated by neurological symptoms as indicated above but starts rather insidiously with poor school performance, inadequate behaviour or psychiatric symptoms [6,16] . There are some examples in which these patients were misdiagnosed as being schizophrenic, depressive or aff ected with Alzheimer disease (e. g. [35,38] ). In most patients, gross motor function becomes mildly impaired with some ' coordination problems ' and neurological signs may include reduced deep tendon refl exes indicating peripheral nerve involvement and also a positive Babinski sign but without much spastic posturing.…”

Late-onset metachromatic leukodystrophy

“…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.…”