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INTRODUCTION: Infantile Systemic Hyalinosis (ISH) is a rare and fatal genetic disorder with mutations in Capillary morphogenesis gene-2 CMG2 / Human anthrax toxin receptor gene-2 ANTXR2 resulting in spindle cell proliferation, altered collagen metabolism with extensive deposition of amorphous eosinophilic PAS positive hyaline material in the connective tissues of various organs. The common presenting features would be progressive stiffness of multiple joints, skin lesions, multiple episodes of protracted infections, prolonged diarrhoea and failure to thrive. ISH is a rapidly progressive painful disorder of infancy with a very short life expectancy. CASE PRESENTATION: 3 months old identical twins born to a 5th degree consanguinous couple were brought with complaints of excessive cry, deformity of all four limbs, recurrent episodes of respiratory tract infections and diarrhoea since birth. Evaluation of both the probands revealed facial dysmorphism with perinasal nodules, gingival hypertrophy, fixed deformities of multiple joints bilaterally, umbilical hernia, fleshy perianal nodules and pigmented patches over knuckles and ankle. A clinical diagnosis of ISH was suspected and confirmed by detection of homozygous c.277_278insATTATTT (or p.L93Yfs*14) in exon 3 of the ANTXR2 gene. The probands were managed symptomatically and parents were counselled regarding prenatal diagnosis in future pregnancies. CONCLUSION: IHS is commonly misdiagnosed as Arthrogryposis Multiplex Congenita and is often mismanaged with manipulation of the stiff joints and invasive surgical procedures. Prenatal diagnosis by chorionic villus biopsy is possible once causative mutation in a family is identified. Invasive surgical interventions for histopathological analysis can be avoided as clinical features are most often classical and genetic analysis is confirmatory. Management is conservative and symptomatic. We report this case of identical twins with features of ISH in view of its rarity as timely clinical suspicion can avoid painful and invasive procedures for diagnosis and management.
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OBJECTIVES: To determine the variables affecting serum 17 hydroxyprogesterone (17OHP) in neonates born at a tertiary hospital in Mumbai, India. METHODS: Serum 17OHP was measured in peripheral venous blood between 3rd to 5th day of life by competitive radioimmunoassay and on follow up at 3 mo of age. Serum 17OHP was compared among four groups [full term healthy(FT), full term stressed(FS), preterm healthy(PT), preterm stressed(PS)] by non-parametric tests (Kruskal Wallis (KW) test and Mann- Whitney (MW) test). Pearson's test was used to correlate natural log of serum 17OHP (ln17OHP) with variables like gestational age, birth weight, stress factor, sex, antenatal administration of glucocorticoids to mothers, Apgar score at 5 min and mode of delivery. Linear regression analysis was done using significant variables in Pearson's test to determine best predictors of ln17OHP. RESULTS: The initial median (number of cases, inter-quartile range) serum 17OHP (ng/ml) for the four groups was as follows; FT 8.4 (33, 6-13); PT 20 (36, 11-29.5); FS 34 (29, 26-45) and PS 58 (24, 40.75-76.5) [total N = 122 newborns, p = 0.001]. Pearson's test showed that gestational age, birth weight, stress factor, Apgar score were negatively correlated with 17OHP whereas stress factor, mode of delivery, use of antenatal steroids in mothers were significantly positively correlated. However, stress factor emerged as the most important significant positive predictor (multiple R = 0.643, P = <0.0001). On follow up at 3 mo age, the median 17OHP (N = 73 newborns) had significantly decreased to normal level. CONCLUSION: Stress due to neonatal illnesses like meconium aspiration, sepsis, birth asphyxia, etc. significantly elevate serum 17OHP and may lead to false positives in newborn screening for congenital adrenal hyperplasia.
