Early clinical symptoms and incidence of aspartylglucosaminuria in Finland

Abstract

Early clinical symptoms were analyzed from all known 43 children with aspartylglucosaminuria, born during 1974-1989 in Finland. Pre- and perinatal histories appeared normal for all children, except for muscular hypotonia and weak sucking in some babies. Three infants had abduction stiffness in the hips, needing follow-up. Other abnormalities found in infancy were umbilical or inguinal hernias and unusual susceptibility to respiratory and ear infections. This susceptibility diminished clearly in most patients after six years of age. Episodic diarrhea, described earlier, appeared to be a rather infrequent symptom and a less valuable diagnostic clue. New clinical phenomena were talipes planovalgus or clubfoot, needing surgical treatment, and aggressive behavior, needing, occasionally, child psychiatric consultation or treatment. In addition, angiokeratoma of the skin, not an infrequent phenomenon among adult patients, was found in one child. The main indications for further studies were delayed speech, attention deficit and clumsy or delayed motor functions. The disease is easily misdiagnosed and, universally, probably underdiagnosed. Its incidence in Finland was recalculated and appeared to be at least 1 in 18,500 live-born babies in this country.

Aspartylglycosaminuria: a review

“…2) are the first symptoms [14] associated to hernias and respiratory infections are the key signs to an early identification of AGU. In childhood AGU appears as delayed speech development, poor motor coordination and exceptional placidity or periods of hyperactivity [15]. On the average, the clinical diagnosis of AGU is made at the age of 5 years.…”

Aspartylglucosaminidase (AGA) is efficiently produced and endocytosed by glial cells: implication for the therapy of a lysosomal storage disorder

“…All patients are severely mentally retarded. Typical and variable connective tissue changes include hernias, feet in the valgus position [35], a large tongue, progressive facial abnormalities, skin problems [36] and chronic arthritis [37]. Changes in the expression and synthesis of extracellular matrix components have been reported [38], also indicating that connective tissue abnormalities are common among AGU patients.…”

“…Elsewhere about 50 patients have been reported. AGU is caused by mutations in the AGA gene in chromosome 4q34- 35. This leads to the dysfunction of aspartylglucosaminidase-enzyme (AGA) [2], a soluble lysosomal hydrolase catalyzing the degradation of glycoproteins [3].…”

Lysosomal storage disorders: Molecular basis and laboratory testing

“…Apart from selected populations presenting a high prevalence for specific diseases, such as the Ashkenazi Jewish population at high risk for Gaucher disease,[18] Tay-Sachs disease and Niemann-Pick disease;[19] the Finnish population with its high incidence of aspartylglucosaminuria[20] and infantile/juvenile neuronal ceroid lipofuscinosis,[21] as far as we know, prevalence data on LSDs, as a group, have only been reported in Greece,[22] the Netherlands,[23] Australia,[24] Portugal[25] and the Czech Republic [26]. As a group, overall incidence of LSDs is estimated at around 1:5,000-1:8,000 [24].…”