RESUMO
BACKGROUND: MIRAGE syndrome is a recently discovered rare genetic disease characterized by myelodysplasia (M), infection (I), growth restriction (R), adrenal hypoplasia (A), genital phenotypes (G), and enteropathy (E), caused by a gain-of-function mutation in the SAMD9 gene. We encountered a girl with molecularly-confirmed MIRAGE syndrome who developed steroid-resistant nephrotic syndrome. CASE PRESENTATION: She was born at 33 weeks gestational age with a birth weight of 1064 g. She showed growth failure, mild developmental delays, intractable enteropathy and recurrent pneumonia. She was diagnosed as MIRAGE syndrome by whole exome sequencing and a novel SAMD9 variant (c.4615 T > A, p.Leu1539Ile) was identified at age four. Biopsied skin fibroblast cells showed changes in the endosome system that are characteristic of MIRAGE syndrome, supporting the genetic diagnosis. Proteinuria was noted at age one, following nephrotic syndrome at age five. A renal biopsy showed focal segmental glomerulosclerosis (FSGS) with immune deposits. Steroid treatment was ineffective. Because we speculated that her nephrosis was a result of genetic FSGS, we decided not to introduce immunosuppressive agents and instead started enalapril to reduce proteinuria. Although her proteinuria persisted, her renal function was normal at age eight. CONCLUSIONS: This is the first detailed report of a MIRAGE syndrome patient with nephrotic syndrome. Because patients with MIRAGE syndrome have structural abnormalities in the endosomal system, we speculate that dysfunction of endocytosis in podocytes might be a possible mechanism for proteinuria.
Assuntos
Inibidores da Enzima Conversora de Angiotensina/uso terapêutico , Enalapril/uso terapêutico , Transtornos da Motilidade Esofágica/complicações , Glomerulosclerose Segmentar e Focal/tratamento farmacológico , Glucocorticoides/uso terapêutico , Transtornos do Crescimento/complicações , Síndromes de Imunodeficiência/complicações , Síndrome Nefrótica/tratamento farmacológico , Transtornos da Motilidade Esofágica/genética , Feminino , Glomerulosclerose Segmentar e Focal/complicações , Glomerulosclerose Segmentar e Focal/genética , Glomerulosclerose Segmentar e Focal/patologia , Transtornos do Crescimento/genética , Humanos , Hipoadrenocorticismo Familiar/complicações , Hipoadrenocorticismo Familiar/genética , Síndromes de Imunodeficiência/genética , Lactente , Infecções , Enteropatias/complicações , Enteropatias/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Mutação , Síndromes Mielodisplásicas/complicações , Síndromes Mielodisplásicas/genética , Síndrome Nefrótica/complicações , Síndrome Nefrótica/genética , Síndrome Nefrótica/patologia , Síndrome , Falha de Tratamento , Anormalidades Urogenitais/complicações , Anormalidades Urogenitais/genética , Sequenciamento do ExomaRESUMO
Primary adrenal insufficiency (PAI) in children is mostly due to genetic defects. The understanding of the molecular genetics of the causes of adrenal insufficiency in the pediatric population has made significant progress during the last years. It has been shown that inherited PAI can lead to certain clinical manifestations and health problems in children beyond the adrenals. Organ dysfunctions associated with different forms of PAI in children include a wide range of organs such as gonads, brain, heart, bone, growth, bone marrow, kidney, skin, parathyroid, and thyroid. Diagnosing the correct genetic cause of PAI in children is therefore crucial to adequately control long-term treatment and follow-up in such patients.