Myoclonus and angiokeratomas in adult galactosialidosis

Abstract

Galactosialidosis is an autosomal recessive lysosomal storage disorder characterized by a combined deficiency of bgalactosidase and a-neuraminidase, due to a defect of another lysosomal protein, cathepsin A. The latter, forms a complex with b-galactosidase and neuraminidase, and protects them against excessive proteolytic degradation. Three clinical phenotypes had been described: a severe early infantile form; a milder late infantile type with minor mental deterioration; and a juvenile/adult form, mainly found in Japan, which is characterized by slowly progressive neurological symptoms, skeletal and eye abnormalities, dysmorphism, angiokeratomas, and long survival.1 Herein, we report a case of galactosialidosis of the juvenile-adult form in a Peruvian girl with angiokeratoma corporis diffusum (ACD) and myoclonus.A 24-year-old woman presented a 5-year history of involuntary movements. At age 19, she developed a progressive myoclonic disorder that started in the lower limbs and caused frequent falls. The myoclonus subsequently spreads to other body regions. Five years into the disease, she was almost wheelchair bound, and other activities such as eating and speaking were considerably affected. There were, however, no seizures or cognitive decline.She was the third child of nonconsanguineous Peruvian parents and had two older sisters, one of which had skin lesions but no abnormal movements. There was no family history of neurological disorders. Further information about ancestor's origins couldn't be obtained, although some oriental features seemed to be present in distant relatives. The patient's developmental milestones were normal and she had a history of anemia and irregular menstrual cycles.Physical examination revealed densely peppered red macules ranging from 1 to 3 mm on palms ( Fig. 1), elbows, knees, oral mucosa, lips, and on thighs and loins in a bathing suit distribution. She had distal transverse reddish bands on her nails and few naevi on her soles. She was short (146 cm) and had course facial features and hypertrichosis. Neurological examination showed mild intellectual dysfunction (IQ, 68), mild sensorineural hearing impairment, and decreased visual acuity. Deep tendon reflexes were brisk. Tone and muscle strength were slightly reduced. She had multifocal, stimulus sensitive myoclonus triggered by action. She had a wide-based-bouncing gait and needed help to walk because of negative myoclonus.The laboratory tests were all normal except for a mild microcytic anemia. Cerebrospinal fluid examination (including lactate levels) and copper metabolism were normal. She had subclinical hypothyroidism but no elevated antithyroid antibodies. Serum gluten antibodies were within normal range. Ophthalmologic examination revealed myopia, mild optic atrophy, reduced visual acuity but no macular cherryred spots. The electroencephalogram was normal. Needle electromyography showed myopathic changes with normal nerve conduction velocities. Muscle biopsy was nonspecific. Median nerve somatosensory evoked potentials were ...

Zolpidem for the Treatment of Neurologic Disorders

“…The Table includes a list of included studies and their characteristics. Most were classified under movement disorders (n = 31) or DOCs (n = 22) . For movement disorders, the most common diagnosis was dystonia (n = 10), including generalized dystonia, cervical dystonia, hand dystonia, tongue dystonia, oromandibular dystonia, blepharospasm, segmental axial dystonia, limb dystonia, spastic dysphonic dystonia, Meige syndrome, myoclonus dystonia syndrome, and Filipino X-linked dystonia .…”

“…For movement disorders, the most common diagnosis was dystonia (n = 10), including generalized dystonia, cervical dystonia, hand dystonia, tongue dystonia, oromandibular dystonia, blepharospasm, segmental axial dystonia, limb dystonia, spastic dysphonic dystonia, Meige syndrome, myoclonus dystonia syndrome, and Filipino X-linked dystonia . Other diagnoses included Parkinson disease (n = 6), progressive supranuclear palsy (n = 6), catatonia (n = 5), postanoxic spasticity (n = 1), tardive dyskinesia (n = 1), central pontine myelinolysis (n = 1), and drug-induced parkinsonism (n = 1) . Studies on DOCs were subdivided into those with patients in the vegetative state (n = 10), minimally conscious state (n = 8), or both vegetative state and minimally conscious state (n = 4) .…”

Juvenile/adult‐onset galactosialidosis with remarkable clinical variabilities in two Japanese siblings

“…The IVS7DS, A‐G, +3 splice site mutation in the CTSA gene was known to cause juvenile/adult‐onset galactosialidosis, which only found in Japan . Juvenile‐onset galactosialidosis was reported worldwide; however, adult‐onset galactosialidosis was only reported in a single subject from Peru other than Japan . Juvenile/adult‐onset galactosialidosis shows characteristic clinical features, such as an angiokeratoma, beaked vertebrae, and cherry‐red spots in optic fundi, combined with neurological findings such as myoclonic jerks, cerebellar ataxia, generalized seizures, mental retardation, and progressive cognitive impairment.…”

“…[3][4][5] Juvenile-onset galactosialidosis was reported worldwide; however, adult-onset galactosialidosis was only reported in a single subject from Peru other than Japan. [6][7][8] The IVS7DS, A-G, +3 mutation in the CTSA gene is A-to-G substitution at the position 3 of the 5′ splice donor site of intron 7, causing skipping of exon 7 in the CTSA messenger RNA. 3,4 The age at onset and clinical progression of juvenile/adult-onset galactosialidosis were reported to have a significant variability among families; however, in the previously reported sibling cases, they were relatively similar within the family (Table 1).…”

How to detect late-onset inborn errors of metabolism in patients with movement disorders – A modern diagnostic approach

“…Sialidosis type 1Initially normal, atrophy (more pronounced in the cerebellum, vermis atrophy) later in disease[43].GalactosialidosisInitially normal, atrophy (more pronounced in the cerebellum, vermis atrophy) later in disease[44,45].Metachromatic leukodystrophyBilateral symmetrical confluent areas of periventricular deep white matter abnormalities. Anterior lesions with sparing of the subcortical U fibers leading to a butterfly pattern in patients with later onset disease.…”