PMC:3506840 / 2431-6569 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3506840","sourcedb":"PMC","sourceid":"3506840","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3506840","text":"Case report\nThe patient, a 25-year-old Japanese woman, the second child of non-consanguineous healthy parents, was born after 39 weeks of gestation with no prenatal or perinatal problems. Her early developmental milestones were normal, except for two episodes of febrile seizures at 1 year of age, which never recurred. From the age of three, her food intake was relatively small, and malnutrition delayed her physical growth, but her mental development was normal. From the age of nine, she suffered from episodic vomiting after eating, which caused anorexia. At the age of 11, she was referred to our hospital for further investigation of progressive weight loss (−1.4 kg/year). Her height was 123 cm (−3.0 SD) and she weighed 18.6 kg (−2.5 SD). She had normal intelligence and no neurological deficits, except for episodic postprandial vomiting. Detailed physical investigations showed no significant abnormalities, except for scoliosis. Gastrointestinal, metabolic, endocrinological and psychological disorders were ruled out. No neurophysiological examinations were performed, although, brain MRI revealed a 7-mm-sized lesion in the posterior dorsal portion of the cervicomedullary junction, which was enhanced with Gd-DTPA (Fig. 1A). Signal changes were also detected bilaterally in the dentate nuclei without enhancement. No other signal abnormalities were noted. During follow-up on MRIs, taken twice a year, the enhancement of the lesion disappeared after 2 years, although the plaque remained. Her episodic vomiting also vanished almost simultaneously. Her growth stopped at the age of 17. At age 25, she is frail 140 cm/33.4 kg with scoliosis. She has normal intelligence and is asymptomatic. A tiny plaque without enhancement, the same size as before, is still visible in the dorsal part of medulla oblongata (Fig. 1C), although cervicomedullary atrophy without a signal change has advanced (Fig. 1B).\nFig. 1 Serial radiological studies. A First MRI of the medulla oblongata (at age 11): axial T2-weighted image (T2-WI) (a), T1-WI (b), and T1-WI with gadolinium enhancement (c) of axial sections. The lesion is 7 mm in size, hyper-intense, but hypo-intense inside on T2-WI (a), iso- to hypo-intense on T1-WI (b), with contrast enhancement (c). Except for the bilateral hilus of the dentate nucleus (same as 14 years later; C-c), no other signal abnormalities were noted (data not shown). The enhancement disappeared 2 years later (data not shown), although, the plaque remains. B Chronological sagittal section of the brainstem MRI at age 11 (a), 16 (b) and 25 (c). Brainstem atrophy is unremarkable at age 11 (a), although, with time, progressive atrophy of medulla oblongata is seen (b, c). The anterior–posterior diameter at the middle of the medulla oblongata was 11.7 mm at age 11 (a), but only 8.8 mm at age 25 (c). C Radiological study at age 25. Axial T2-WI (a–c). Moderate atrophy of cervical spinal cord (a) and medulla (b) are seen. A small plaque in the dorsal part of medulla oblongata (b) without contrast enhancement (data not shown) remains, although its size has not changed since age 11 (A-a). The hilus of the dentate nucleus is hyper-intense bilaterally without enhancement (data not shown), although, no other signal change is detected in the brainstem (c). No pontine or midbrain atrophy, abnormalities in the basal ganglia, “ventricular garlands” or leukodystrophy in deep white matter were observed (data not shown). Mild scoliosis was also observed in this patient (d)\nSequencing of the GFAP gene with informed consent revealed a heterozygous missense mutation in exon 5 (c.827G\u003eT), causing a change of arginine to leucine at amino acid position 276 (p.R276L). The mutation was not found in her mother. The father, who died in traffic accident in his forties, could not be investigated. This mutation has already been described as responsible for pathologically proven hereditary [4] and sporadic [5] cases of adult-onset AxD. According to an interview, there was no relationship between the present patient and the families previously reported, although they originated from the same region of Japan.","divisions":[{"label":"title","span":{"begin":0,"end":11}},{"label":"p","span":{"begin":12,"end":3505}},{"label":"figure","span":{"begin":1914,"end":3505}},{"label":"label","span":{"begin":1914,"end":1920}},{"label":"caption","span":{"begin":1921,"end":3505}},{"label":"p","span":{"begin":1921,"end":3505}}],"tracks":[{"project":"AxD_symptoms","denotations":[{"id":"T12","span":{"begin":263,"end":279},"obj":"Phenotype"},{"id":"T13","span":{"begin":385,"end":397},"obj":"Phenotype"},{"id":"T14","span":{"begin":506,"end":523},"obj":"Phenotype"},{"id":"T15","span":{"begin":551,"end":559},"obj":"Phenotype"},{"id":"T16","span":{"begin":653,"end":664},"obj":"Phenotype"},{"id":"T17","span":{"begin":839,"end":847},"obj":"Phenotype"},{"id":"T18","span":{"begin":930,"end":939},"obj":"Phenotype"},{"id":"T19","span":{"begin":1508,"end":1525},"obj":"Phenotype"},{"id":"T20","span":{"begin":1644,"end":1653},"obj":"Phenotype"},{"id":"T21","span":{"begin":2578,"end":2595},"obj":"Phenotype"},{"id":"T22","span":{"begin":3323,"end":3357},"obj":"Phenotype"},{"id":"T23","span":{"begin":3385,"end":3399},"obj":"Phenotype"},{"id":"T24","span":{"begin":3458,"end":3467},"obj":"Phenotype"}],"attributes":[{"id":"A22","pred":"hp_id","subj":"T22","obj":"http://purl.obolibrary.org/obo/HP_0002134"},{"id":"A13","pred":"hp_id","subj":"T13","obj":"http://purl.obolibrary.org/obo/HP_0004395"},{"id":"A14","pred":"hp_id","subj":"T14","obj":"http://purl.obolibrary.org/obo/HP_0002572"},{"id":"A23","pred":"hp_id","subj":"T23","obj":"http://purl.obolibrary.org/obo/HP_0002415"},{"id":"A18","pred":"hp_id","subj":"T18","obj":"http://purl.obolibrary.org/obo/HP_0002650"},{"id":"A21","pred":"hp_id","subj":"T21","obj":"http://purl.obolibrary.org/obo/HP_0007366"},{"id":"A17","pred":"hp_id","subj":"T17","obj":"http://purl.obolibrary.org/obo/HP_0002013"},{"id":"A20","pred":"hp_id","subj":"T20","obj":"http://purl.obolibrary.org/obo/HP_0002650"},{"id":"A24","pred":"hp_id","subj":"T24","obj":"http://purl.obolibrary.org/obo/HP_0002650"},{"id":"A16","pred":"hp_id","subj":"T16","obj":"http://purl.obolibrary.org/obo/HP_0001824"},{"id":"A15","pred":"hp_id","subj":"T15","obj":"http://purl.obolibrary.org/obo/HP_0002039"},{"id":"A12","pred":"hp_id","subj":"T12","obj":"http://purl.obolibrary.org/obo/HP_0002373"},{"id":"A19","pred":"hp_id","subj":"T19","obj":"http://purl.obolibrary.org/obo/HP_0002572"},{"subj":"T12","pred":"source","obj":"AxD_symptoms"},{"subj":"T13","pred":"source","obj":"AxD_symptoms"},{"subj":"T14","pred":"source","obj":"AxD_symptoms"},{"subj":"T15","pred":"source","obj":"AxD_symptoms"},{"subj":"T16","pred":"source","obj":"AxD_symptoms"},{"subj":"T17","pred":"source","obj":"AxD_symptoms"},{"subj":"T18","pred":"source","obj":"AxD_symptoms"},{"subj":"T19","pred":"source","obj":"AxD_symptoms"},{"subj":"T20","pred":"source","obj":"AxD_symptoms"},{"subj":"T21","pred":"source","obj":"AxD_symptoms"},{"subj":"T22","pred":"source","obj":"AxD_symptoms"},{"subj":"T23","pred":"source","obj":"AxD_symptoms"},{"subj":"T24","pred":"source","obj":"AxD_symptoms"}]},{"project":"2_test","denotations":[{"id":"22198646-12447932-75888807","span":{"begin":3918,"end":3919},"obj":"12447932"}],"attributes":[{"subj":"22198646-12447932-75888807","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"AxD_symptoms","color":"#e793ec","default":true},{"id":"2_test","color":"#93eccd"}]}]}}