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David P Bick, MD @DavidPBick

Clinical & lab geneticist using genomics to help families find answers. Now @genomicsengland working on screening newborns for treatable genetic disorders.

Joined November 2021
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Will parents want newborn screening for a condition such as hypophosphatasia that may not affect their child before the child is an adult? It is treated with asfotase alfa. Treatment for the condition is expensive. ncbi.nlm.nih.gov/books/NBK47…

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Which genetic conditions should be screened for in newborns? Hypophosphatasia is a condition resulting in easily broken bones and other problems. A severe, sometimes lethal form occurs at birth. Milder forms occur in children and adults. pubmed.ncbi.nlm.nih.gov/3488…

Hypophosphatasia - PubMed

Hypophosphatasia (HPP) is an inherited metabolic disease caused by loss-of-function mutations in the tissue non-specific alkaline phosphatase (TNAP) gene. Reduced activity of TNAP leads to the...

pubmed.ncbi.nlm.nih.gov
Hyperprolinemia type II due to ALDH4A1 is treated with vitamin B6 (pyridoxine). Newborn screening would allow families to prevent the seizures associated with this illness rather than wait for them to occur. pubmed.ncbi.nlm.nih.gov/3403…

Metabolic epilepsy in hyperprolinemia type II due to a novel nonsense ALDH4A1 gene variant - PubMed

Hyperprolinemia type II (HPII) is a rare autosomal recessive disorder of proline degradation pathway due to deficiency of delta-1-pyrroline-5-carboxylate dehydrogenase. Pathogenic variants in the...

pubmed.ncbi.nlm.nih.gov
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Newborn screening finds genetic disorders needing immediate treatment. Families also find it valuable to uncover and treat conditions that appear in the first few years. For example, hyperprolinemia type II due to changes in ALDH4A1 starts months after birth, with seizures.
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GOT2 deficiency is treated with vitamin B6 (pyridoxine) and the amino acid, serine. It was only recently discovered so not a lot is known about long-term outcome. pubmed.ncbi.nlm.nih.gov/3399…

Inborn disorders of the malate aspartate shuttle - PubMed

Over the last few years, various inborn disorders have been reported in the malate aspartate shuttle (MAS). The MAS consists of four metabolic enzymes and two transporters, one of them having two...

pubmed.ncbi.nlm.nih.gov
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Glutamic-oxaloacetic transaminase 2 deficiency due to changes in the gene GOT2 affects brain development, causing severely impaired intellectual development, spasticity and seizures. Specific treatment very early appears to help.
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Pyridoxine-dependent epilepsy (PDE) due to errors in the gene PNPO is treated with pyridoxine (vitamin B6) like 2 other genes, PLPBP & ALDH7A1. PDE ranges from 1/20,000 to 1/783,000 live births. orpha.net/consor/cgi-bin/OC_…
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Pyridoxine-dependent epilepsy due to errors in the gene PNPO is a genetic condition that needs to be treated immediately, soon after birth. Untreated it leads to brain damage.
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Children with pyridoxine-dependent epilepsy due to errors in the gene PLPBP need to be treated right away because left untreated they will have brain damage. For some, unfortunately, early treatment does not always work. We still have lots to learn. pubmed.ncbi.nlm.nih.gov/3342…

Vitamin B6-dependent epilepsy due to pyridoxal phosphate-binding protein (PLPBP) defect - First...

Vitamin B6-dependent epilepsy due to PLPBP defect is an important differential diagnosis to consider in patients with biochemical features suggestive of pyridoxamine 5'-phosphate Oxidase (PNPO)...

pubmed.ncbi.nlm.nih.gov
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Different genetic conditions that need urgent treatment soon after birth sometimes use the same treatment. Pyridoxine-dependent epilepsy due the gene ALDH7A1 is treated with pyridoxine (vitamin B6). This is true for pyridoxine-dependent epilepsy due to the gene PLPBP, as well.
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Children with pyridoxine-dependent epilepsy develop seizures that can start very soon after birth. Left untreated this leads to brain damage. Treatment, as early as possible, with pyridoxine (vitamin B6) and diet is essential for the best outcome. pubmed.ncbi.nlm.nih.gov/3320…

Consensus guidelines for the diagnosis and management of pyridoxine-dependent epilepsy due to...

Pyridoxine-dependent epilepsy (PDE-ALDH7A1) is an autosomal recessive condition due to a deficiency of α-aminoadipic semialdehyde dehydrogenase, which is a key enzyme in lysine oxidation. PDE-ALDH7A1...

pubmed.ncbi.nlm.nih.gov
There are a number of genetic disorders that may require urgent treatment in a newborn very soon after birth. Not all are part of a newborn screening at present. One example is pyridoxine-dependent epilepsy due to errors in a gene, ALDH7A1.
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MCADD is a problem of fat metabolism. Between meals our body uses fat to provide energy but in MCADD the individual can't convert fat to energy fast enough. So, with infections or prolonged fasting these children become ill. Treatment is simple: give extra sugar (glucose).
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Some of the genetic disorders sought by newborn screening have a very simple treatment. Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency or MCADD for short is an example. nhs.uk/conditions/mcadd/. About 1 in 10K children have this.

MCADD: detailed information

gov.uk
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Hematopoietic stem cell transplantation slows but does not stop Krabbe disease progression, even when used in asymptomatic newborns.
Treatment for the infantile onset form of Krabbe disease is hematopoietic stem cell transplantation (bone marrow transplant), a procedure that can be associated with serious complications. www-sciencedirect-com.ezprox…
Krabbe disease is a neurodegenerative disease that results from a deficit of the galactosylceramidase enzyme. About 1 in 100K children are born with this.
The purpose of newborn screening is to provide a treatment when it will be most helpful. But some treatments are more risky than others.
This is why some newborn programs screen for Pompe disease and some do not. pompediseasenews.com/2020/02….
The screening test finds children who will develop disease quickly. They need treatment. But it also finds some children who will not have disease until they are adults. They may not need treatment right away. ncbi.nlm.nih.gov/pmc/article…

Variable clinical features and genotype-phenotype correlations in 18 patients with late-onset Pompe...

Pompe disease is a lysosomal storage disorder caused by the deficiency of enzyme acid alpha-glucosidase (GAA) which results in accumulation of glycogen, particularly in the skeletal, cardiac, and...

pmc.ncbi.nlm.nih.gov
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