Prenatal bilateral adrenal calcifications, hypogonadism, and nephrotic syndrome: beyond Wolman disease

Abstract

What's already known about this topic? Prenatal bilateral adrenal calcifications are a rare prenatal finding. Adrenal calcifications may be seen with intrauterine infections, tumor, or in Wolman disease. Risk factors for adrenal calcifications include large birth weight, hypoxia, septicemia, coagulation defects, and thromboembolism. The association of adrenal calcifications and proteinuria has been published in two reports of four different patients.What does this study add? We propose that the constellation of bilateral adrenal calcifications, micropenis, testicular dysfunction, increased fetal nuchal translucency, and congenital nephrotic syndrome represents a new clinical entity. The consanguinity in this family suggests an autosomal recessive inheritance of this disease. This entity should be considered in the differential diagnosis of bilateral adrenal calcifications.

Deficiency of the sphingosine-1-phosphate lyase SGPL1 is associated with congenital nephrotic syndrome and congenital adrenal calcifications

“…The association of CNS and adrenal calcifications was reported in two male cousins (patient 1 and 2) from a consanguineous Arab family (family 1; Fig. A) (Schreyer‐Shafir et al., ).…”

“…The association of congenital proteinuria and adrenal calcifications is very rare and was first reported in three patients of American Indian origin (Powers, Cohen, & Williams, 1990), and later in an Indian patient with CNS, adrenal calcifications, and a cardiac malformation (Indumathi, Dinakar, Lewin, & Phadke, 2005), and in two patients who were first cousins (Schreyer-Shafir et al, 2014). One male patient had nonpalpable testes and micropenis, and another patient had pericardial and pleural effusions, generalized hydrops, and a cleft palate.…”

Congenital adrenal calcifications as the first clinical indication of sphingosine lyase insufficiency syndrome: A case report and review of the literature

“…SGPL1 was first identified as the molecular cause of SPLIS in 2017 in two large cohorts (Lovric et al, 2017;Prasad et al, 2017) The first cases that clinically resembled SPLIS, with CNS and congenital adrenal calcifications, were reported in 1990 in three Indigenous American patients (Powers et al, 1990) and subsequently in 2005 in India (Indumathi et al, 2005). In 2014, two additional cases were reported in a consanguineous Arab pedigree from Israel; molecular confirmation was obtained a few years later in 2017 (Janecke et al, 2017;Schreyer-Shafir et al, 2014). Since that time, several additional cases of this childhood syndrome have been reported (Table 1) (Bamborschke et al, 2018;Janecke et al, 2017;Linhares et al, 2018;Maharaj et al, 2020;Martin et al, 2020).…”