Screening

The lysosomal storage diseases (LSDs) are inherited disorders; genetic counsellors should be involved in screening family members.[90]

Neonatal diagnosis of metabolic diseases is possible by screening of blood spots that are taken from all infants during the first weeks of life in Western Europe and in North America; these samples are used to diagnose phenylketonuria, hypothyroidism, and haemoglobinopathies. Neonatal screening programmes aimed at whole populations have not generally been adopted for the LSDs. Pilot screening programmes have begun in several US states and in various countries worldwide.[91][92]​ Screening is available in some countries for newborns with laboratory results or family history suggestive of an LSD.[93]

Pre-symptomatic diagnosis of LSDs is entirely feasible but is not universally practised. There are strong arguments in favour of implementing programmes for diseases such as Pompe, where early diagnosis is important to allow timely institution of specific therapy.[36]​ Several US states, Taiwan, Austria, Italy, Hungary, and Japan are piloting newborn screening for Pompe disease.[91]

There are significant ethical considerations for other LSDs: for example, Gaucher disease, where neonatal screening would lead to detection of large numbers of people who may only become symptomatic in middle age, if at all.[78][94]​​​ A neonatal screening study of Fabry disease showed an incidence of 1 in 3200, but only 1 of 12 children detected had a mutation that has previously been shown to be associated with disease; the remainder were mutations of unknown clinical significance.[15]

The technology (e.g., using blood spots) is well developed for mucopolysaccharidosis (MPS) disorders, Fabry, and Gaucher diseases. Tandem mass spectrometry is available for Pompe disease and MPS II. A 6-month nationwide screening study in Austria found a higher than expected number of infants with a mutation for a lysosomal storage disorder, suggesting that population screening might pose challenges for the healthcare system.[95]

Screening in high-risk populations

Informal screening programmes are already offered by some communities. The Ashkenazi Jewish communities in New York and London offer a service screening potential partners for Gaucher and Tay-Sachs diseases.

Some experts advise that a more comprehensive screening panel should be undertaken particularly in those of Ashkenazi descent, to include less common conditions including Gaucher disease and Niemann-Pick's disease.[96]​

Screening for Fabry disease in high-risk populations is also advocated.[97]​ Various studies have screened for Fabry disease among high-risk populations (e.g., patients undergoing dialysis, those with cryptogenic stroke, and those with left ventricular hypertrophy).[44]​​

Detection of carriers

Family screening should only be undertaken after appropriate consultation with a clinical geneticist. Carriers may be diagnosed by DNA and/or enzyme assay; in X-linked LSDs, female heterozygotes can only be reliably diagnosed by DNA tests. Clinical assessment is necessary to distinguish late-onset homozygous sufferers from carriers, and consultant referral may be required.

If an individual is found to be a carrier for a specific condition, the individual’s reproductive partner should be offered appropriate counselling regarding potential outcomes, and genetic testing.[96]​ If both partners are found to be carriers of a genetic condition, genetic counselling should be offered. Antenatal diagnosis and reproductive techniques should be discussed to reduce the risk of an affected offspring.[96]

The American College of Obstetrics and Gynecologists (ACOG) recommends offering screening in the Ashkenazi Jewish population when considering pregnancy or during pregnancy for certain genetic conditions, including Tay-Sachs disease.[96] ACOG also recommends screening for Tay-Sachs disease if either member of a couple is French-Canadian or Cajun descent.[96]​​​

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