RESUMO
We report 27 children, aged 14 months to 9 years, who had megalencephaly, hypotonia, proximal muscle weakness, speech and motor delay, and increased intracellular lipid (myoliposis) in needle muscle biopsy specimens. The patients had many features of the Ruvalcaba-Myhre-Smith syndrome, and in 17 families we confirmed the autosomal dominant inheritance pattern previously suggested. Muscle carnitine content was low in all 11 patients and all 4 affected relatives tested. All 27 probands were treated with oral L-carnitine; a clinical response was noted in 17. We speculate that myoliposis may be found in other disorders with megalencephaly and muscle symptoms. In such cases, muscle carnitine deficiency should be considered. The reason for the reduced muscle carnitine content is not known.
Assuntos
Anormalidades Múltiplas/diagnóstico , Encéfalo/anormalidades , Carnitina/deficiência , Gigantismo/diagnóstico , Doenças Musculares/diagnóstico , Anormalidades Múltiplas/tratamento farmacológico , Anormalidades Múltiplas/metabolismo , Anormalidades Múltiplas/patologia , Administração Oral , Biópsia por Agulha , Carnitina/administração & dosagem , Carnitina/metabolismo , Criança , Pré-Escolar , Feminino , Gigantismo/tratamento farmacológico , Gigantismo/metabolismo , Gigantismo/patologia , Histocitoquímica , Humanos , Lactente , Metabolismo dos Lipídeos , Masculino , Músculos/metabolismo , Músculos/patologia , Doenças Musculares/tratamento farmacológico , Doenças Musculares/metabolismo , Doenças Musculares/patologia , SíndromeRESUMO
We describe a relatively new syndrome in four children with characteristic facial dysmorphism, sensorineural hearing loss, severe visual impairment with retinitis pigmentosa, hypotonia, hepatomegaly, and severe developmental delay. Two patients had intracranial hemorrhage secondary to a vitamin K-responsive clotting defect; both had steatorrhea. Liver biopsy specimens in two children showed an accentuated lobular architecture with prominent fibrous bands in the portal area. In one, the ultrastructure showed accumulation of abnormal substances and occasional trilaminar structures in hepatocytes and other cells. All four patients had elevated serum phytanic acid concentrations (0.3 to 2.7 mg/dl, normal less than 0.2 mg/dl) and deficient fibroblast phytanic acid oxidase activity (0.1 to 6.7 pmol/mg protein/hr, normal 23 to 87 pmol/mg protein/hr). Serum pipecolic acid was 7 to 55 times normal, and the ratio of C26/C22 very long chain fatty acids was increased (0.10 to 0.22; normal less than 0.03). This characteristic syndrome has been described in several children and called infantile Refsum disease or phytanic acid storage disease. Its relationship to neonatal adrenoleukodystrophy, hyperpipecolic acidemia, and Zellweger syndrome is discussed.