Two Japanese cases with aspartylglycosaminuria: clinical and morphological features

Abstract

Two members of a consanguineous Japanese family with a clinical picture of aspartylglycosaminuria (AGU) are described. Both patients exhibited mental retardation, coarse facial features, angiokeratoma and myoclonic seizures. Biochemical studies showed elevated excretion of urinary sialyloligosaccharides and decreased activity of aspartylglycosaminidase in lymphoblasts. Morphologic studies of skin biopsy specimens showed many clear vacuoles mainly in the vascular endothelial cells and secretory cells of the sweat glands. Osmiophilic lamellar cytoplasmic inclusions were also noted in the ganglion cells in rectal biopsy. The ethnic distribution of AGU may be more widespread than previously suspected and appears not to be restricted to Finnish populations. Ours are the first Japanese patients diagnosed as AGU. We conclude that AGU should also be included in the differential diagnosis of mentally retarded patients in Asian countries.

Aspartylglucosaminuria: Clinical Presentation and Potential Therapies

“…For example, a Qatari AGU patient presented with severe muscular hypotonia, scarce spontaneous movements, multiple contractures, and respiratory insufficiency, 8 whereas hearing loss was detected in 8 Palestinian patients from 3 unrelated families 16,17 as well as 1 Canadian AGU patient. 27 In addition, angiokeratoma and myoclonic seizures were observed in a Japanese patient, 10 -12 hepatosplenomegaly in 2 Chinese patients, 21 viral myocarditis with congestive heart failure in a white patient from the United States, 13,22 macroorchidism in 3 Puerto Rican patients, 28,49 and angiokeratoma corporis diffusum in an Italian patient 29,30 and a Spanish patient 31 have been observed.…”

“…Worldwide, more than 30 AGA variants have been identified in patients with diverse ethnicities (Table 1). Of these AGA variants, approximately 50% are missense mutations (eg, c.439T>C [p.S147P] in a Qatari patient 8 ) with the remaining mutations consisting of microdeletions (eg, Del T787 in a patient from Mauritania 9 ) and insertions (eg, 7-nucleotide insertion between exons 3 and 4 in a Japanese patient 10 -12 ) as well as splice mutations, gross deletions, and complex rearrangements (eg, Del 807-940, resulting in the exclusion of exon 8 in an African American patient 13,14 ). One missense mutation, c.302C>T (p.A101 V), was detected in an AGU patient from Italy and another from England.…”

Aspartylglucosaminuria

“…4 Nevertheless, the disease has been accepted to be panethnic, with cases reported in various European countries, Japan, Palestine, Tunisia, as well as Central and North America. 5 –13 To date, 1 Turkish patient is described in the literature. 14…”