RESUMEN
INTRODUCTION: Lipin-1 deficiency is a major cause of rhabdomyolysis that are precipitated by febrile illness. The prognosis is poor, with one-third of patients dying from cardiac arrest during a crisis episode. Apart from acute rhabdomyolysis, most patients are healthy, showing normal clinical and cardiac ultrasound parameters. PATIENTS AND METHODS: We report cardiac and exercise examinations of 8 children carrying two LPIN1 mutations. The examinations were performed outside of a myolysis episode, but one patient presented with fever during one examination. RESULTS: All but one patient displayed normal resting cardiac function, as determined by echocardiography. One patient exhibited slight left ventricular dysfunction at rest and a lack of increased stroke volume during cycle ramp exercise. During exercise, peripheral muscle adaptation was impaired in 2 patients compared to healthy controls: they presented an abnormal increase in cardiac output relative to oxygen uptake: dQ/dVO2=8.2 and 9.5 (>2DS of controls population). One patient underwent 2 exercise tests; during one test, the patient was febrile, leading to acute rhabdomyolysis in the following hours. He exhibited changes in recovery muscle reoxygenation parameters and an increased dQ/dVO2 during exercise compared with that under normothermia (7.9 vs 6), which did not lead to acute rhabdomyolysis. The four patients assessed by cardiac 1H-magnetic resonance spectroscopy exhibited signs of intracardiac steatosis. CONCLUSION: We observed abnormal haemodynamic profiles during exercise in 3/8 patients with lipin-1 deficiency, suggesting impaired muscle oxidative phosphorylation during exercise. Fever appeared to be an aggravating factor. One patient exhibited moderate cardiac dysfunction, which was possibly related to intracardiac stored lipid toxicity.
Asunto(s)
Ejercicio Físico/fisiología , Corazón/fisiopatología , Fosfatidato Fosfatasa/genética , Rabdomiólisis/genética , Adolescente , Estudios de Casos y Controles , Niño , Ecocardiografía , Prueba de Esfuerzo , Femenino , Voluntarios Sanos , Corazón/diagnóstico por imagen , Humanos , Masculino , Mutación , Consumo de Oxígeno , Fosfatidato Fosfatasa/deficiencia , Espectroscopía de Protones por Resonancia Magnética , Rabdomiólisis/fisiopatología , Volumen SistólicoRESUMEN
Propionic acidemia is the result of a deficiency in propionyl-CoA carboxylase activity. Chronic neurologic and cognitive complications frequently occur, but the psychiatric evolution of the disorder is not well documented. We conducted a pedopsychiatric evaluation of 19 children, adolescents and young adults, aged between 2 and 25 years, using ADI-R, CARS-T, as well as ADOS when autism spectrum disorder was suspected. Previous psychometric examinations were also taken into consideration. Thirteen patients had an IQ < 80. Two patients presented with autism and two additional patients with other autism spectrum disorders. Five patients did not fulfill diagnostic criteria for autism spectrum disorder but showed difficulties indicative of a broader autism phenotype (BAP). Four other patients had severe anxiety manifestations related to their disease. Two patients presented with acute psychotic episodes. The number of decompensations in the first 3 years of life was lower in patients with autism spectrum disorder or related symptoms. These patients were also older when they were assessed (median age of 15 years old versus 11 years old). There was no significant correlation between 3-hydroxypropionate levels during the first 6 years of life and autism spectrum disorder diagnosis. In conclusion, autism spectrum disorder is frequent in patients with propionic acidemia. These patients should undergo in-depth psychiatric evaluation and be screened for autism spectrum disorder. Further studies are needed to understand the underlying mechanisms.
Asunto(s)
Trastorno del Espectro Autista/diagnóstico , Acidemia Propiónica/diagnóstico , Adolescente , Adulto , Trastorno del Espectro Autista/genética , Niño , Preescolar , Femenino , Humanos , Discapacidad Intelectual/etiología , Ácido Láctico/análogos & derivados , Ácido Láctico/metabolismo , Masculino , Metilmalonil-CoA Descarboxilasa/genética , Acidemia Propiónica/genética , Adulto JovenAsunto(s)
Anomalías Múltiples/sangre , Gránulos Citoplasmáticos/ultraestructura , Granulocitos/ultraestructura , Linfocitos/ultraestructura , Enfermedades por Almacenamiento Lisosomal/sangre , Consanguinidad , Resultado Fatal , Glicosaminoglicanos/orina , Humanos , Recién Nacido , Enfermedades por Almacenamiento Lisosomal/orina , Masculino , Vacuolas/ultraestructuraRESUMEN
Supravalvular aortic aneurysms are less frequent than abdominal ones. Among Supravalvular aortic aneurysm aetiologies, we focused on dystrophic lesions as they can be secondary to genetic causes such as elastin anomaly. We report on a familial 7q11.23 triplication - including the ELN gene - segregating with a supravalvular aortic aneurysm. During her first pregnancy, our index patient was diagnosed with tuberous sclerosis and with a Supravalvular aortic aneurysm. The foetus was affected equally. For the second pregnancy, parents applied for preimplantation diagnosis, and a subsequent prenatal diagnosis was offered to the couple, comprising TSC1 molecular analysis, karyotype, and multiplex ligation probe amplification. TSC1 mutation was not found on foetal deoxyribo nucleic acid. Foetal karyotype was normal, but multiplex ligation probe amplification detected a 7q11.23 duplication. Quantitative-polymerase chain reaction and array-comparative genomic hybridisation carried out to further assess this chromosome imbalance subsequently identified a 7q11.23 triplication involving ELN and LIMK1. Foetal heart ultrasound identified a Supravalvular aortic aneurysm. A familial screening was offered for the 7q11.23 triplication and, when found, heart ultrasound was performed. The triplication was diagnosed in our index case as well as in her first child. Of the 17 individuals from this family, 11 have the triplication. Of the 11 individuals with the triplication, 10 were identified to have a supravalvular aortic aneurysm. Of them, two individuals received a medical treatment and one individual needed surgery. We provide evidence of supravalvular aortic aneurysm segregating with 7q11.23 triplication in this family. We would therefore recommend cardiac surveillance for individuals with 7q11.23 triplication. It would also be interesting to offer a quantitative-polymerase chain reaction or an array-comparative genomic hybridisation to a larger cohort of patients presenting with isolated supravalvular aortic aneurysm, as it may provide further information.
Asunto(s)
Aneurisma de la Aorta Torácica/genética , Predisposición Genética a la Enfermedad/genética , Esclerosis Tuberosa/genética , Adulto , Anciano , Aneurisma de la Aorta Torácica/complicaciones , Niño , Preescolar , Femenino , Humanos , Lactante , Recién Nacido , Masculino , Persona de Mediana Edad , Hibridación de Ácido Nucleico , Reacción en Cadena de la Polimerasa , Embarazo , Diagnóstico Prenatal , Esclerosis Tuberosa/complicaciones , Ultrasonografía Prenatal , Adulto JovenAsunto(s)
Acetil-CoA C-Aciltransferasa/deficiencia , Acidosis , Errores Innatos del Metabolismo de los Aminoácidos/diagnóstico , Cuerpos Cetónicos/sangre , Vómitos , Acetoacetatos/orina , Acetil-CoA C-Aciltransferasa/sangre , Acetil-CoA C-Aciltransferasa/orina , Acidosis/sangre , Acidosis/complicaciones , Acidosis/orina , Errores Innatos del Metabolismo de los Aminoácidos/sangre , Errores Innatos del Metabolismo de los Aminoácidos/orina , Glicina/análogos & derivados , Glicina/orina , Humanos , Hidroxibutiratos/orina , Lactante , Masculino , Vómitos/sangre , Vómitos/etiología , Vómitos/orinaRESUMEN
Mucopolysaccharidosis type I-H (MPS I-H) is a rare lysosomal storage disorder caused by α-L-Iduronidase deficiency. Early haematopoietic stem cell transplantation (HSCT) is the sole available therapeutic option to preserve neurocognitive functions. We report long-term follow-up (median 9 years, interquartile range 8-16.5) for 51 MPS I-H patients who underwent HSCT between 1986 and 2018 in France. 4 patients died from complications of HSCT and one from disease progression. Complete chimerism and normal α-L-Iduronidase activity were obtained in 84% and 71% of patients respectively. No difference of outcomes was observed between bone marrow and cord blood stem cell sources. All patients acquired independent walking and 91% and 78% acquired intelligible language or reading and writing. Intelligence Quotient evaluation (n = 23) showed that 69% had IQ ≥ 70 at last follow-up. 58% of patients had normal or remedial schooling and 62% of the 13 adults had good socio-professional insertion. Skeletal dysplasia as well as vision and hearing impairments progressed despite HSCT, with significant disability. These results provide a long-term assessment of HSCT efficacy in MPS I-H and could be useful in the evaluation of novel promising treatments such as gene therapy.