# NEWBORN SCREENING PILOT STUDY FOR EXPANDED GROUP OF HOMOCYSTINURIA (HCU)-RELATED DISORDERS (TERNED "EXPANDED HCU")

> **NIH NIH N01** · EMORY UNIVERSITY · 2020 · $926,734

## Abstract

The goal of newborn screening (NBS) is to detect potentially fatal or disabling conditions in 
newborns, thereby providing a window of opportunity for early treatment, often while the child is 
still asymptomatic. Such early detection and treatment can have a profound impact on the clinical 
severity of the condition in the  affected child. If left undiagnosed and untreated, the 
consequences of the targeted disorders can be dire,   many causing irreversible neurological 
damage, intellectual, developmental and physical disabilities, and   even death. In 2006, the 
American College of Medical Genetics (ACMG) developed newborn screening  guidelines that recommend 
that all newborn infants be screened for 29 "core conditions" and that 26  secondary conditions 
identified during the core evaluations be reported as part of the Recommended Uniform Screening 
Panel (RUSP). These recommendations have   been accepted by the HHS Secretary's Advisory Committee 
on Heritable Disorders in Newborns and  Children (ACHDNC) (authorized by the Children's Health Act 
of 2000), and by the Secretary of HHS. Since acceptance of the core conditions, 6 additional 
conditions have been added. Most states now use this or very similar panels for newborn screening. 
Currently, there are thousands of  rare disorders that have been identified and hundreds that could 
potentially benefit from newborn  screening.

Classic homocystinuria (often abbreviated as HCU) is the most common genetic disorder of sulfur 
metabolism and is inherited in an autosomal recessive manner. This disorder is caused by deficiency 
of the cystathionine beta-synthase enzyme and is characterized by visual changes, skeletal 
problems, vascular changes, and problems in the central nervous system. Its metabolic hallmark is 
an increased excretion of homocysteine in the urine and elevated levels of homocysteine (HCY) in 
the plasma and other tissues.
Treatment includes the dietary protein/methionine restriction, and supplementation with B vitamins 
and/or betaine. Early intervention appears to make a significant difference in reducing 
complications and improving outcomes. There is a milder and later-onset form, associated with less 
severe mutations in the causative gene, characterized as pyridoxine-responsive. Although known to 
be rare, the prevalence of HCU ranges from 1/20,000-1/344,000; however, due to a founder effect and 
high rates of consanguinity in Qatar, the prevalence rate is 1/1800 in that country, and the 
disease is a classic severe form. HCU is a primary condition that was adopted at the inception of 
the RUSP. Each state in the United States screens for classic homocystinuria in newborns, typically 
by measuring elevated methionine (Met) using tandem mass spectrometry (TMS) on dried blood spots. 
However, Met is a surrogate metabolite for HCY, and may not be elevated in the immediate postnatal 
period depending on the age and nutritional status of the infant; if a baby has had minimal di...

## Key facts

- **NIH application ID:** 10271525
- **Project number:** 275201500001I-0-759402000001-1
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** WILLIAM WILCOX
- **Activity code:** N01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $926,734
- **Award type:** —
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271525

## Citation

> US National Institutes of Health, RePORTER application 10271525, NEWBORN SCREENING PILOT STUDY FOR EXPANDED GROUP OF HOMOCYSTINURIA (HCU)-RELATED DISORDERS (TERNED "EXPANDED HCU") (275201500001I-0-759402000001-1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10271525. Licensed CC0.

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