Considering Proximal Urea Cycle Disorders in Expanded Newborn Screening.

Tania Vasquez-Loarte,J Lawrence Merritt,John D Thompson

doi:10.3390/ijns6040077

Abstract

Proximal urea cycle disorders (PUCDs) have adverse outcomes such as intellectual disability and death, which may benefit from newborn screening (NBS) through early detection and prevention with early treatment. Ornithine transcarbamylase deficiency (OTCD) and carbamoyl phosphate synthetase 1 deficiency (CPS1D) are screened in six and eight states in the United States. We analyzed current evidence to see if it supports inclusion of PUCDs in the NBS panels based upon prevention potential, medical, diagnostic, treatment, and public health rationales. A literature review was performed in PubMed using MESH terms for OTCD, CPS1D, and NAGSD. A systematic review was performed in the hallmark of NBS inclusion criteria. We reviewed 31 articles. Molecular and biochemical diagnosis is available to provide diagnostic evidence. Untreated PUCDs have a significant burden with considerable developmental delay and mortality that may improve with early treatment. Tandem mass spectrometry can be used for NBS for PUCDs; however, citrulline and glutamine alone are not specific. Medical treatments currently available for PUCDs meet existing medical, diagnostic, treatment, and public health rationales. Improvement in NBS algorithms to increase sensitivity and specificity will allow earlier diagnosis and treatment to potentially improve disability and mortality rates.

Highlights

Newborn screening (NBS) is a population-based, preventive public health approach aimed at the early identification and treatment of certain diseases that otherwise are lethal or chronic and disabling [1]
We report our findings from a retrospective review of currently available literature relating to Proximal urea cycle disorders (PUCDs) and their inclusion in NBS—using the principles and rationale from Washington State as proof of concept
Ornithine transcarbamylase deficiency (OTCD) is the most common PUCD having an approximate incidence of 1:56,500 (Table S3), making it similar in order, or more common, than many other commonly accepted distal Urea cycle disorders (UCDs) and non-UCD NBS conditions currently in many NBS panels [13]

Summary

Introduction

Newborn screening (NBS) is a population-based, preventive public health approach aimed at the early identification and treatment of certain diseases that otherwise are lethal or chronic and disabling [1]. In Washington State, the Board of Health oversees which diseases are included in the NBS panel in compliance with the Revised Code of Washington (RCW 70.83.050). In this way, it nominates an Advisory Committee for the evaluation of each candidate condition. It nominates an Advisory Committee for the evaluation of each candidate condition This evaluation is guided by three main principles: (1) the decision should be supported by evidence; (2) there should be universal accessibility to diagnostic and therapeutic services; and (3) the advantages of screening for a disease should exceed the potential harms to children, their families, and society.

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