RESUMEN
BACKGROUND: Special diet with restricted branched-chain-amino-acids used for treating maple syrup urine disease can lead to specific amino acid deficiencies. CASE CHARACTERISTICS: We report a neonate who developed skin lesions due to isoleucine deficiency while using specialised formula. INTERVENTION/OUTCOME: Feeds were supplemented with expressed breast milk. This caused biochemical and clinical improvement with resolution of skin lesions. MESSAGE: Breast milk is a valuable and necessary adjunct to specialized formula in maple syrup urine disease to prevent specific amino acid deficiency in the neonatal period.
Asunto(s)
Isoleucina , Enfermedad de la Orina de Jarabe de Arce , Acrodermatitis , Lactancia Materna , Diagnóstico Diferencial , Humanos , Fórmulas Infantiles , Recién Nacido , Isoleucina/administración & dosificación , Isoleucina/deficiencia , Enfermedad de la Orina de Jarabe de Arce/dietoterapia , Enfermedad de la Orina de Jarabe de Arce/genética , Enfermedad de la Orina de Jarabe de Arce/fisiopatología , Zinc/deficienciaRESUMEN
We present a 32-year-old patient who, from age 7 months, developed photophobia, left-eye ptosis and progressive muscular weakness. At age 7 years, she showed normal psychomotor development, bilateral ptosis and exercise-induced weakness with severe acidosis. Basal blood and urine lactate were normal, increasing dramatically after effort. PDHc deficiency was demonstrated in muscle and fibroblasts without detectable PDHA1 mutations. Ketogenic diet was ineffective, however thiamine gave good response although bilateral ptosis and weakness with acidosis on exercise persisted. Recently, DLD gene analysis revealed a homozygous missense mutation, c.1440 A>G (p.I480M), in the interface domain. Both parents are heterozygous and DLD activity in the patient's fibroblasts is undetectable. The five patients that have been reported with DLD-interface mutations suffered fatal deteriorations. Our patient's disease is milder, only myopathic, more similar to that due to mutation p.G229C in the NAD(+)-binding domain. Two of the five patients presented mutations (p.D479V and p.R482G) very close to the present case (p.I480M). Despite differing degrees of clinical severity, all three had minimal clues to DLD deficiency, with occasional minor increases in α-ketoglutarate and branched-chain amino acids. In the two other patients, hypertrophic cardiomyopathy was a significant feature that has been attributed to moonlighting proteolytic activity of monomeric DLD, which can degrade other mitochondrial proteins, such as frataxin. Our patient does not have cardiomyopathy, suggesting that p.I480M may not affect the DLD ability to dimerize to the same extent as p.D479V and p.R482G. Our patient, with a novel mutation in the DLD interface and mild clinical symptoms, further broadens the spectrum of this enzyme defect.
Asunto(s)
Acidosis Láctica/genética , Enfermedad de la Orina de Jarabe de Arce/genética , Debilidad Muscular/genética , Mutación Missense , Ácido Tióctico/análogos & derivados , Acidosis Láctica/diagnóstico , Acidosis Láctica/tratamiento farmacológico , Acidosis Láctica/enzimología , Acidosis Láctica/fisiopatología , Adulto , Secuencia de Aminoácidos , Secuencia de Bases , Biomarcadores/sangre , Biomarcadores/orina , Blefaroptosis/diagnóstico , Blefaroptosis/enzimología , Blefaroptosis/genética , Células Cultivadas , Análisis Mutacional de ADN , Suplementos Dietéticos , Femenino , Predisposición Genética a la Enfermedad , Herencia , Heterocigoto , Homocigoto , Humanos , Ácido Láctico/sangre , Ácido Láctico/orina , Enfermedad de la Orina de Jarabe de Arce/diagnóstico , Enfermedad de la Orina de Jarabe de Arce/tratamiento farmacológico , Enfermedad de la Orina de Jarabe de Arce/enzimología , Enfermedad de la Orina de Jarabe de Arce/fisiopatología , Datos de Secuencia Molecular , Fuerza Muscular/genética , Debilidad Muscular/diagnóstico , Debilidad Muscular/tratamiento farmacológico , Debilidad Muscular/enzimología , Debilidad Muscular/fisiopatología , Linaje , Fenotipo , Fotofobia/diagnóstico , Fotofobia/enzimología , Fotofobia/genética , Estructura Terciaria de Proteína , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/diagnóstico , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/enzimología , Enfermedad por Deficiencia del Complejo Piruvato Deshidrogenasa/genética , España , Tiamina/uso terapéutico , Ácido Tióctico/química , Ácido Tióctico/deficiencia , Ácido Tióctico/genética , Resultado del TratamientoAsunto(s)
Enfermedad de la Orina de Jarabe de Arce/diagnóstico , Enfermedad de la Orina de Jarabe de Arce/terapia , Aminoácidos de Cadena Ramificada/sangre , Suplementos Dietéticos , Femenino , Humanos , Enfermedad de la Orina de Jarabe de Arce/fisiopatología , Persona de Mediana Edad , Factores de Tiempo , Resultado del TratamientoRESUMEN
The clinical problems, dietary management and biochemical monitoring over a 40-year period of the longest-surviving patient with maple syrup urine disease are described. Her case illustrates that a good outcome can be obtained with early diagnosis and institution of a diet restricted in branched-chain amino acids. Changes in dietary supplementation have benefited her in terms of nutrition and quality of life. Consistently high blood concentrations of branched-chain amino acids have not been associated with neuropsychometric decline.