We have read with great interest Rasmussen et al.'s report of two sisters with Aicardi-Goutières syndrome (AGS) with cerebral thrombotic microangiopathy, one of whom had antiphospholipid antibodies [[ 1 ]]. As the authors pointed out, their observation adds to a previous similar report of two siblings [[ 6 ]]. We would like to describe a further patient with clinical and biological signs of systemic lupus erythematosus (SLE) and an AGS-like picture that improved markedly on corticosteroids and her sister with similar features consistent with AGS. The propositus presented at seven months with a skin rash and feeding difficulties. She was born at 37 weeks gestation from healthy consanguineous parents from Pakistan. Birth weight was 2700 g, height was 47.5 cm, and head circumference 33 cm. She has two healthy older brothers, a brother with a poorly documented history of severe developmental delay who died in status epilepticus at the age of 19 months, a brother with congenital cardiomyopathy and squamous skin lesions of unknown etiology, and one sister described below. Investigations and availability of information regarding the other family members have been limited by poor parental collaboration. At presentation, she had failure to thrive including microcephaly, poor interaction, quadriplegia with spasticity and generalized dystonia, chronic otorrhea, interstitial pneumopathy, and scaly erythematous plaques extending over the whole body. The following investigations were normal: hemogram, liver enzymes, serum lactate, plasma and urine aminoacids, urine organic acids, karyotype, toxoplasma, Rubella and herpes simplex serology, biotinidase, arylsulfatase and cerebroside-β-galactosidase activities and isoelectrofocussing of sialotransferrins. Total IgG levels were 1.9 g/dL (0.3 - 1.7 g/dL) and IgM 1.0 g/dL (0 - 0.2 g/dL). Cerebrospinal fluid cell count, protein level, and electrophoresis, glucose, and lactate were normal as well as neurotransmitters. Magnetic resonance imaging (MRI) performed at eight months showed diffuse hypomyelination. Skin biopsy showed monocytic inflammation in the superficial dermis. Cultured fibroblasts showed normal growth under UV exposure. Additional immunological investigations obtained at the age of two years showed antinuclear factor titer at 1 : 2500, anti-mDNA antibody 1 : 80, anti-double stranded DNA 1 : 140, anti-nucleosome 6.4 BI, negative anti-RNP, anti-RO, anti-LA, anti-SCL70, and antimyelin antibodies. Anticardiolipin antibodies, and complement were normal. Repeat brain MRI showed cortical atrophy, hypomyelination, and abnormal signal in putamina (Fig. [ 1 ]) corresponding to the calcifications seen on computed tomography (Fig. [ 2 ]). Fig. 1 a - c MRI of the index case at six years of age showing cortical atrophy, hypomyelination, and abnormal signal in putamina. a T2-weighted image; b FLAIR sequence; c recovery inversion. Fig. 2 CT of index case at 3 years of age showing bilateral basal ganglia calcifications. She received prednisolone (1 mg/kg/d) and azathioprin (2 mg/kg/d). On this treatment, the skin rash disappeared, otorrhea resolved, and pulmonary function markedly improved with disappearance of radiographic interstitial infiltrate. Concomitantly, there was marked improvement in interaction and motor control, with the emergence of social smile, vocalizing, and eye pointing, voluntary axial righting, improvement of muscle tone, and the emergence of manipulation skills. However, head growth profile remained subnormal, with aggravating microcephaly (e.g., 45.5 cm at five years). Incidental treatment discontinuation was associated with resumption of the rash, pneumopathy, and neurological deterioration. At the age of six, while she was on immunosuppressive treatment, she presented acutely with severe hemolytic anemia (Hb 2.9 g/dL). Direct Coombs test and cold agglutinins were positive. Reticulocyte level was 35 %. Continuing hemolysis was noted following blood transfusion. After prednisolone increase to 2 mg/kg/d, hemoglobulinemia stabilized at normal values. Interferon-alpha levels measured at six years of age while the patient was receiving corticosteroids were very high in the serum and cerebrospinal fluid (199 and 121 pg/mL, respectively; normally undetectable in the cerebrospinal fluid). The patient's sister was followed up from birth. Birth weight and height were normal but she had microcephaly, which became more marked as she grew (e.g., 44 cm at 28 months). She showed ichthyosis, irritability, and severe hypotonia. This was gradually replaced by quadriplegia with both spastic and dystonic features. She had mild oculomotor apraxia. Investigations performed in the neonatal period showed severe thrombocytopenia, normal liver enzymes, serum lactate, amino acids, acylcarnitine profile, urine organic acids, and mucopolysaccharides, no antinuclear antibodies, normal complement, markedly increased serum interferon-alpha (250 pg/mL), interventricular septal hypertrophy on echocardiography, linear hyperechogenic areas in the basal ganglia, and diffuse hyperechogenicity of the periventricular white matter on cerebral ultrasound. MRI showed diffuse swelling of the frontal and parieto-occipital white matter bilaterally. At the age of one year, she has marked developmental delay with severe axial hypotonia and mixed-type quadriplegia, and has shown little developmental change since then. Cerebrospinal fluid examination showed normal cell count. Repeat MRI performed at the age of 17 months showed cortico-subcortical atrophy, delayed myelination, and abnormal signals in the caudates and putamina consistent with calcifications (Fig. [ 3 ]). Fig. 3 a - d Sister's MRI performed at the age of 17 months showing cortico-subcortical atrophy, delayed myelination and abnormal signals...