RESUMEN
Mutations in AarF domain-containing kinase 3 (ADCK3) are responsible for the most frequent form of hereditary coenzyme Q10 (CoQ10) deficiency (Q10 deficiency-4), which is mainly associated with autosomal recessive cerebellar ataxia type 2 (ARCA2). Clinical presentation is characterized by a variable degree of cerebellar atrophy and a broad spectrum of associated symptoms, including muscular involvement, movement disorders, neurosensory loss, cognitive impairment, psychiatric symptoms and epilepsy. In this report, we describe, for the first time, a case of photoparoxysmal response in a female patient with a mutation in ADCK3. Disease onset occurred in early childhood with gait ataxia, and mild-to-moderate degeneration. Seizures appeared at eight years and six months, occurring only during sleep. Photoparoxysmal response was observed at 14 years, almost concomitant with the genetic diagnosis (c.901C>T;c.589-3C>G) and the start of CoQ10 oral supplementation. A year later, disease progression slowed down, and photosensitivity was attenuated. A review of the literature is provided focusing on epileptic features of ADCK3-related disease as well as the physiopathology of photoparoxysmal response and supposed cerebellar involvement in photosensitivity. Moreover, the potential role of CoQ10 oral supplementation is discussed. Prospective studies on larger populations are needed to further understand these data.
Asunto(s)
Ataxia Cerebelosa , Epilepsia Refleja , Proteínas Mitocondriales/genética , Ubiquinona/análogos & derivados , Adolescente , Ataxia Cerebelosa/complicaciones , Ataxia Cerebelosa/tratamiento farmacológico , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/fisiopatología , Epilepsia Refleja/tratamiento farmacológico , Epilepsia Refleja/etiología , Epilepsia Refleja/genética , Epilepsia Refleja/fisiopatología , Femenino , Humanos , Imagen por Resonancia Magnética , Ubiquinona/farmacologíaRESUMEN
The basal ganglia and thalami are paired deep grey matter structures with extensive metabolic activity that renders them susceptible to injury by various diseases. Most pathological processes lead to bilateral lesions, which may be symmetric or asymmetric, frequently showing characteristic patterns on imaging studies. In this comprehensive pictorial review, the most common and/or typical genetic, acquired metabolic/toxic, infectious, inflammatory, vascular and neoplastic pathologies affecting the central grey matter are subdivided according to the preferential location of the lesions: in the basal ganglia, in the thalami or both. The characteristic imaging findings are described with emphasis on the differential diagnosis and clinical context.
Asunto(s)
Ganglios Basales/patología , Encefalopatías/diagnóstico por imagen , Encefalopatías/patología , Sustancia Gris/patología , Tálamo/patología , Diagnóstico Diferencial , HumanosRESUMEN
BACKGROUND: In GM1 gangliosidosis the lack of function of ß-galactosidase results in an accumulation of GM1 ganglioside and related glycoconjugates in visceral organs, and particularly in the central nervous system, leading to severe disability and premature death. In the type 2 form of the disease, early intervention would be important to avoid precocious complications. To date, there are no effective therapeutic options in preventing progressive neurological deterioration. Substrate reduction therapy with Miglustat, a N-alkylated sugar that inhibits the enzyme glucosylceramide synthase, has been proposed for the treatment of several lysosomal storage disorders such as Gaucher type 1 and Niemann Pick Type C diseases. However, data on Miglustat therapy in patients with GM1 gangliosidosis are still scarce. METHODS: We report here the results of Miglustat administration in four Italian children (average age: 55 months, range 20-125) affected by GM1 gangliosidosis type 2 treated in three different Italian pediatric hospitals specialized in metabolic diseases. CONCLUSION: This treatment was safe and relatively well tolerated by all patients, with stabilization and/or slowing down of the neurological progression in three subjects.
Asunto(s)
1-Desoxinojirimicina/análogos & derivados , Gangliosidosis GM1/tratamiento farmacológico , Inhibidores de Glicósido Hidrolasas/uso terapéutico , 1-Desoxinojirimicina/efectos adversos , 1-Desoxinojirimicina/farmacología , 1-Desoxinojirimicina/uso terapéutico , Adolescente , Sistema Nervioso Central/diagnóstico por imagen , Sistema Nervioso Central/efectos de los fármacos , Niño , Preescolar , Tolerancia a Medicamentos , Femenino , Glucosiltransferasas/antagonistas & inhibidores , Glucosiltransferasas/metabolismo , Inhibidores de Glicósido Hidrolasas/efectos adversos , Inhibidores de Glicósido Hidrolasas/farmacología , Humanos , Lactante , MasculinoRESUMEN
Pyruvate dehydrogenase complex (PDHC) deficiency causes encephalomyopathies, of which there are four major categories: (1) neonatal encephalopathy with lactic acidosis; (2) an early infantile form, which (3) at times resembles Leigh syndrome; and (4) a later-onset form. Long-term clinical and radiological follow-up is still incompletely elucidated. We report a 12-year-old male with intermittent-relapsing PDHC deficiency who presented with three typical acute episodes of metabolic decompensation over 7 years. Neuroimaging showed reversible signal abnormalities in the basal ganglia, inferior olivary nuclei, periaqueductal grey matter, and dentate nuclei, with evidence of lactate on magnetic resonance spectroscopy. Molecular analysis of PDH1A revealed a novel hemizygous c.1045G>A mutation, predicting a p.A349T missense mutation. He was treated with thiamine supplementation and, while on this regimen, he experienced several intercurrent febrile episodes without neurological compromise. This case report stresses the importance of performing neuroimaging during acute clinical episodes because brain lesions in PDHC deficiency may be transient and reversible, and false-negative results may mislead the diagnosis and delay the treatment.