Congenital Disorders of Glycosylation, Peroxisomal Disorders, and Smith-Lemli-Opitz Syndrome

This chapter covers a broad range of genetic disorders that can present in the newborn period including peroxisomal disorders, congenital disorders of glycosylation, and Smith-Lemli-Opitz syndrome. The chapter focuses on the clinical presentations in the neonate and infant, diagnostic methods, and treatment options for these disorders. The phenotypic presentation of congenital disorders of glycosylation is broad ranging from mild to severe and from single organ system to multisystem involvement. Congenital disorders of glycosylation should be considered in any unexplained clinical condition, but especially in multisystemic, neurologic conditions. Most diagnoses occur via molecular testing. Treatment is largely supportive with rare exceptions where nutritional supplements have improved symptoms. Peroxisomal disorders are a heterogeneous group of disorders resulting from the absence or dysfunction of one or more peroxisomal enzymes. Features are varied, but include craniofacial dysmorphism, neurologic dysfunction, hepato-digestive dysfunction, renal cysts, and skeletal abnormalities. Diagnosis is best made by next-generation sequencing following screening biochemical tests. Treatment is largely symptomatic and supportive except for hematopoietic stem cell transplant in the cerebral form of X-linked adrenoleukodystrophy that is included in the newborn screen in many states. Smith-Lemli-Opitz (SLO) syndrome is a multisystemic, developmental, and dysmorphic syndrome caused by a defect in cholesterol biosynthesis. Diagnosis is based on finding elevated 7-dehydrocholesterol and 8-dehydrocholoesterol levels in the blood. Treatment involves cholesterol supplementation with supportive care.