ABSTRACT
The etiology of molar incisor hypomineralization (MIH) is unclear. Our hypothesis was that certain antibiotics cause MIH. We examined 141 schoolchildren for MIH and, from their medical files, recorded the use of antibiotics under the age of 4 yrs. MIH was found in 16.3% of children. MIH was more common among those children who had taken, during the first year of life, amoxicillin (OR=2.06; 95% CI, 1.01-4.17) or the rarely prescribed erythromycin (OR=4.14; 95% CI, 1.05-16.4), compared with children who had not received treatment. Mouse E18 teeth were cultured for 10 days with/without amoxicillin at concentrations of 100 microg/mL-4 mg/mL. Amoxicillin increased enamel but not dentin thickness. An altered pattern of amelogenesis may have interfered with mineralization. We conclude that the early use of amoxicillin is among the causative factors of MIH.
Subject(s)
Amelogenesis/drug effects , Amoxicillin/adverse effects , Anti-Bacterial Agents/adverse effects , Dental Enamel Hypoplasia/chemically induced , Tooth Calcification/drug effects , Animals , Child , Erythromycin/adverse effects , Female , Humans , Incisor/pathology , Male , Mice , Mice, Inbred Strains , Molar/pathology , Retrospective StudiesABSTRACT
OBJECTIVE: To show that the head may shrink in adult patients with aspartylglucosaminuria (AGU), a neurodegenerative disease. METHOD: The head circumference (HC) of 40 adult patients (age at baseline 15 to 47) was measured twice with an interval of 10 years. Of these 40, 21 aged 15-47 and 19 young patients aged 5-14 as well as 40 healthy controls underwent lateral cephalometric radiography. RESULTS: During 10 years' follow-up, the HC of 26 (65%) had decreased by 1 to 4.5 cm (mean 1.7, P < 0.001). Evaluation of lateral skull radiographs revealed that patients aged 15 or more had significantly thicker skulls than did younger patients (P = 0.015). Mean intracranial length (glabella-opisthocranium) of the patients aged 15 or more was significantly shorter than in patients aged 14 years or less (P = 0.029). These measurements indicated that brain volume had decreased. CONCLUSIONS: Macrocephalia in childhood followed by reduced brain volume in adulthood is evident in patients with AGU and is reflected by a decrease in head size.
Subject(s)
Acetylglucosamine/analogs & derivatives , Aspartylglucosaminuria , Lysosomal Storage Diseases/diagnosis , Microcephaly/diagnosis , Acetylglucosamine/urine , Adolescent , Adult , Aged , Aspartylglucosylaminase/genetics , Cephalometry , Child , Child, Preschool , Dementia/diagnosis , Dementia/genetics , Disease Progression , Female , Follow-Up Studies , Humans , Lysosomal Storage Diseases/genetics , Male , Microcephaly/urine , Reference ValuesABSTRACT
UNLABELLED: Descriptions of the outcome of aspartylglucosaminuria (AGU) were analysed, and a comprehensive summary table of symptoms and signs by age was designed. CONCLUSION: The multifarious progressive nature of AGU is obvious in the skills and abilities of patients, as well as in their personality, general health and physical appearance.
Subject(s)
Aspartylglucosylaminase/genetics , Aspartylglucosylaminase/urine , Genetic Predisposition to Disease , Metabolism, Inborn Errors/epidemiology , Metabolism, Inborn Errors/genetics , Adolescent , Adult , Aspartylglucosaminuria , Child , Child, Preschool , Disease Progression , Female , Finland/epidemiology , Humans , Incidence , Infant, Newborn , Male , Metabolism, Inborn Errors/diagnosis , Middle Aged , Risk AssessmentABSTRACT
Rapid infantile growth was the first clinical sign in patients (n = 51) with aspartylglycosaminuria, a lysosomal storage disorder. Even if young children with aspartylglycosaminuria were tall for their age, an early but weak pubertal growth spurt in both sexes resulted in reduced adult heights.
Subject(s)
Acetylglucosamine/analogs & derivatives , Growth , Lysosomal Storage Diseases/physiopathology , Puberty/physiology , Acetylglucosamine/urine , Adolescent , Adult , Child , Child, Preschool , Female , Finland , Humans , Infant , Infant, Newborn , Lysosomal Storage Diseases/urine , Male , MenarcheABSTRACT
Aspartylglucosaminuria (AGU) is a lysosomal storage disorder caused by deficiency of aspartylglucosaminidase (AGA). The main symptom is progressive mental retardation. A spectrum of different mutations has been reported in this disease, one missense mutation (Cys163Ser) being responsible for the majority of Finnish cases. We were able to examine 66 Finnish AGU patients for changes in the oral mucosa and 44 of these for changes in facial skin. Biopsy specimens of 16 oral lesions, 12 of them associated with the teeth, plus two facial lesions were studied histologically. Immunohistochemical staining for AGA was performed on 15 oral specimens. Skin was seborrhoeic in adolescent and adult patients, with erythema of the facial skin already common in childhood. Of 44 patients, nine (20%) had facial angiofibromas, tumours primarily occurring in association with tuberous sclerosis. Oedemic buccal mucosa (leucoedema) and gingival overgrowths were more frequent in AGU patients than in controls (p<0.001). Of 16 oral mucosal lesions studied histologically, 15 represented fibroepithelial or epithelial hyperplasias and were reactive in nature. Cytoplasmic vacuolisation was evident in four. Immunohistochemically, expression of AGA in AGU patients' mucosal lesions did not differ from that seen in corresponding lesions of normal subjects. Thus, the high frequency of mucosal overgrowth in AGU patients does not appear to be directly associated with lysosomal storage or with alterations in the level of AGA expression.
Subject(s)
Acetylglucosamine/analogs & derivatives , Aspartylglucosaminuria , Lysosomal Storage Diseases/pathology , Mouth Mucosa/pathology , Skin/pathology , Acetylglucosamine/urine , Adolescent , Adult , Angiofibroma/pathology , Aspartylglucosylaminase/analysis , Aspartylglucosylaminase/genetics , Child , Child, Preschool , Face , Facial Neoplasms/pathology , Fibroma/pathology , Finland , Gingiva/pathology , Humans , Immunohistochemistry , Lysosomal Storage Diseases/enzymology , Lysosomal Storage Diseases/genetics , Middle Aged , Mouth Mucosa/enzymology , Skin Neoplasms/pathologyABSTRACT
OBJECTIVE: The aim of this study was to assess the oral health of patients with aspartylglucosaminuria, a heritable lysosomal storage disorder, and to recommend guidelines for treatment. STUDY DESIGN: Eighty-two patients with aspartylglucosaminuria and 122 control subjects were examined clinically; in addition, panoramic radiographs were evaluated in 61 patients with aspartylglucosaminuria and 61 control subjects. RESULTS: High prevalences of caries, gingivitis, and oral Candida (P < .001), extensive gingival overgrowths (18%; P < .001), benign odontogenic tumors or tumorlike lesions (8%; P = .057), reduced maxillary sinuses (P < .001), limited mouth opening (P < .001), and food retention in the mouth (45%) were the major oral findings that distinguished the patients with aspartylglucosaminuria from the control subjects. Adults with aspartylglucosaminuria had diverse oral health problems, early loss of several permanent teeth being the most disabling feature. CONCLUSIONS: Patients with aspartylglucosaminuria appear to be at a higher risk for a number of oral disorders; however, poor oral hygiene and failure to cooperate increase these patients' risk of dental and periodontal diseases, making successful prevention crucial.
Subject(s)
Aspartylglucosaminuria , Lysosomal Storage Diseases/complications , Mouth Diseases/etiology , Acetylglucosamine/urine , Adolescent , Adult , Aged , Alveolar Bone Loss/diagnostic imaging , Case-Control Studies , Child , Child, Preschool , DMF Index , Dental Caries/etiology , Female , Finland , Humans , Male , Middle Aged , Mouth Neoplasms/etiology , Odontogenic Tumors/etiology , Oral Hygiene Index , Periodontal Diseases/etiology , Periodontal Index , Radiography , Tooth Loss/etiologyABSTRACT
Aspartylglucosaminuria (AGU) is a lysosomal storage disorder with progressive mental retardation as a presenting manifestation. The disorder is caused by a single nucleotide change in the gene encoding aspartylglucosaminidase (AGA). This rare disease is relatively common in Finland: we were able to examine 81 Finnish AGU-patients for dental and oral changes. Tooth crown size and crown shape were normal, but dental malocclusions were common, and prevalences of spacing, large overjet, anterior open bite, and lateral crossbite exceeded Finnish population prevalences (P < 0.0001). Dental arches were already large in childhood, and in adult patients, when compared to Finnish population standards, the lower dental arch was larger in all dimensions (P < 0.001). Almost all patients had abnormally large tongues, which we assumed to be the reason for the structural abnormalities observed.
