NOVA - Genetic Screening Test for Newborns and Children

NOVA – Genetic Screening Test for Newborns and Children

We know how important early detection and accurate diagnosis is when it comes to rare diseases in children. That’s why we’re proud to offer the Nova test – a state-of-the-art genetic screening solution for children that provides comprehensive insights into your clinical picture. Using next-generation sequencing (NGS) technology, our test goes beyond the standard offerings of the Ministry of Health.

The Nova test has been carefully designed to identify a wide range of rare genetic disorders and equip individuals and families with the knowledge they need to make informed decisions for their health. This innovative approach not only improves detection capabilities, but also provides greater depth of analysis to ensure the highest quality testing.

With its commitment to excellence and appropriate patient care, the Nova test combines advanced science with compassionate support. Thanks to the Nova test, the future of personal and preventative medicine is in your hands.

Discover the benefits of the Nova Test and take proactive steps to understand your health and the health of your loved ones today!

We have collected the most frequently asked questions about the Nova test for you. Our answers will help you understand what Nova is and
why it is performed. At the same time, we present the broader context of screening tests.

List of questions:

What are rare diseases?
What is a diagnostic odyssey?
What is the Nova test?
Why is this test important?
Is newborn screening a new concept?
How many diseases is my child tested for?
What if my child seems completely healthy and children in our family have never had these problems?
How is the test done?
When will I get my results?
What should I do to have my child tested with the Nova test?
Does a repeat test mean my child may have a disease?
What if my child has one of these conditions?
My child is sick. Will my future children have this disease too?
What are the contraindications to performing the test?

Answers:

What are rare diseases?

A rare disease is a disease that occurs with a frequency of less than 1 in 2,000 people (5 in 10,000 people) in the European population. Due to the large number of rare diseases, up to 6-8% of the population is affected by them. About 350 million people worldwide live with a rare disease, about 30 million in the European Union and 2-3 million in Poland.

The clinical diversity of rare diseases is very wide: they can be syndromes and isolated developmental disorders, mental disabilities, neurological, cardiological, nephrological, endocrine, gastroenterological, dermatological, ophthalmological, oncological, immunological or infectious diseases. 80% of rare diseases are genetic, and over 50% (up to 70%) affect children.

What is a diagnostic odyssey?

The diagnosis of a rare disease is difficult. Many patients are condemned to a years-long diagnostic odyssey before a correct diagnosis is made. This is a problem for rare disease patients all over the world. Even in countries where medical care is at a very high level, before the introduction of modern genetic diagnostics, the correct diagnosis of a patient with a rare disease was (on average) only made by the eighth specialist, and by then the patient had already had 2-3 misdiagnoses.

What is the Nova test?

After birth, during hospitalization, blood is taken from the newborn for screening tests offered by the Ministry of Health of the Republic of Poland as part of its pro-health policy. The newborns are tested for possible rare diseases, of which the list in the 2019-2026 program includes 30 (including 11 genes that are tested for mutations).

An extension of these screening tests is the NOVA test, which is even more comprehensive.

1) Nova is a new screening test on the Polish market, which represents an almost fourfold expansion of the screening tests offered as part of the government’s newborn screening program in Poland for 2019-2026.
2) Nova uses next-generation sequencing (NGS) to detect 254 disease entities in 112 rare disease categories by analyzing 264 genes.
3) Nova is primarily intended for children up to 5 years of age (including newborns immediately after birth, without the mother having to start breastfeeding). In justified cases, older children and even adults can also use the test.
4) Nova analyzes the DNA isolated from a dry drop of blood. For a complete analysis, 3-4 drops of blood collected on a tissue paper are sufficient after a painless puncture of the child’s heel or finger.

The aim of the test is to make a quick diagnosis and initiate appropriate prevention or treatment. The result of the NOVA test provides information on whether the child has a mutation in any of the genes tested. In the case of a mutation, it is determined whether it affects the child’s current health or whether the child is only a carrier of the mutation (the disease does not cause symptoms but can be passed on to offspring).

Why is this test important?

Many congenital diseases are very insidious. Their symptoms may not appear immediately, and they do not cause any changes in the appearance of the child. A newborn may therefore receive a score of 10 on the Apgar scale, and symptoms appear slowly over the following months or even years and may include immunological problems, diarrhea, excessive vomiting, drowsiness, skin rashes, seizures, epilepsy, delayed mental and physical development. These symptoms are so non-specific that it can take a long time for the correct diagnosis to be made, by which time it may be too late for effective treatment. This can be avoided, as many congenital diseases can be treated before dangerous symptoms appear.

Thanks to modern medicine, many children can develop normally, provided the disease is detected early. Thanks to our tests, we are able to determine whether a child has a genetic mutation that is characteristic of the disease area we are testing for and inform the doctor about the need for additional tests and special care for the child. In most cases, it is very important to start treatment before the child develops symptoms or becomes ill. Diseases detected by the test have a genetic basis and are inherited from parents who may be carriers of the disease and do not have to show symptoms of the disease due to two sets of genes.

Note: Not all diseases can be completely prevented by early treatment. However, in most cases, prompt treatment allows the affected child to develop normally. In recent decades, the life expectancy of patients with incurable diseases has increased spectacularly, and thanks to new causal therapies, the disease has a chance of turning from incurable to chronic. Therefore, early diagnosis, treatment and prevention are a chance for a long life for the patient.

Is newborn screening a new concept?

No. The concept of screening dates back to the 1950s , and the first analyses that formed the basis of these studies date back to the 1930s and Dr. Asbjorn Folling laboratory, a physician and biochemist working at the Medical Academy in Oslo. He was the first to isolate phenylpyruvic acid, which occurs in elevated concentrations in patients with phenylketonuria. Dr. Folling’s discovery increased the interest of doctors in this disease. In subsequent years, Dr. George Jervis from New York discovered that patients inherit a defect in which the liver is unable to break down phenylalanine (one of the basic amino acids found in all protein-containing foods) into tyrosine and other substances needed for the proper functioning of the body. Dr. Jervis discovered that the result of this defect is the accumulation of phenylalanine in the blood and the secretion of pyruvic acid in the urine, which in turn causes a significant slowdown in the development of the sick child, leading to profound mental retardation.

These beginnings laid the foundation for current screening tests for rare diseases, the list of which continues to grow. Depending on the country and region, screening tests offered as part of local health policies of ministries of health check for from a dozen to several dozen diseases. Screening tests are performed because the detected developmental defects are practically unrecognizable during a medical examination, and left untreated lead to impaired mental and physical development. Only early treatment can save a child from severe mental retardation or numerous hospitalizations without establishing the correct diagnosis.

How many diseases is my child tested for?

The NOVA test offers much more than the government’s newborn screening program in Poland for the years 2019-2026. The Nova test examines 264 genes for mutations leading to 254 disease entities, classified into 112 disease categories.

It is important to remember that detecting a mutation in a gene does not always lead to disease. If a mutation occurs, it is determined whether it affects the child’s current health or whether the child is only a carrier of the mutation (the disease does not cause any symptoms but can be passed on to offspring).

What if my child seems completely healthy and children in our family have never had these problems?

Most babies detected in newborn screening programs show no symptoms at birth and appear healthy. With the Nova test, we can expand the standard screening offer by almost four times and determine if a child may have one of these rare diseases, inform the doctor about the need for additional testing and provide special care for the child.

All of the diseases on the Nova test panel are genetic and are inherited from parents. Every child has two sets of genes – one from mom and one from dad. Sometimes the problem is with just one set of genes, but because the other is fine, the child is not sick. Such children are called carriers. Although the child does not get sick, it means that at least one parent (and sometimes both) is also a carrier. In general, newborn screening tests can identify carriers of some genetic conditions in specific cases, but the program is not designed to detect all carriers. If your child is a carrier, genetic counseling should be sought, as most parents who are carriers are unaware of this. Seeing a doctor will help you understand the information you get.

A negative screening result in one child does not guarantee that subsequent children will be negative. Children and parents can be carriers of diseases even if no one in the family has the disease. Each of these diseases is very rare and there is a good chance that the child will be healthy, but it cannot be ruled out that the disease will occur in another child.

How is the test done?

A referral for testing is prescribed by a physician who is knowledgeable about Nova. Why is it organized this way? We want the doctor to know the possibilities and limitations of the Nova test, and to consciously conduct a conversation with the parents/guardians of the child who is to be tested. During this conversation, the doctor will first confirm whether the child can undergo the Nova test (there are several contraindications, which we write about below), inform what the test involves, present important information related to the results, fill out the test order form and familiarize with the Nova test documentation.

The child will then be referred to a healthcare facility where specialized staff will take a blood sample. Three-four drops are enough to be transferred to a special card with blood-absorbing paper. Blood will be taken from a finger or heel. The puncture is performed using a special lancet or needle that painlessly and extremely quickly cuts the skin (we have tested this many times and we know that it does not hurt). The Nova test documentation will also be completed, and one copy will be given to the parents/guardians. The sample will be sent by courier to the laboratory on the same day (in justified cases samples can be sent within a few days – don’t worry, a dry blood drop is very stable and is protected against degradation, which is why we allow samples to be sent within a few days after the sample has been taken). The shipment is marked as ‘ Medical Express ‘ and the sample is delivered to the laboratory very quickly.

After receiving the sample, the laboratory isolates DNA from a dry blood drop and performs an analysis using next-generation sequencing (NGS). 264 genes are analyzed, and a report is prepared based on the results, which is sent to the doctor who ordered the test. The doctor then discusses the results and presents solutions, if necessary.

When will I get my results?

The laboratory will prepare the report within 25 business days of receiving the sample. This time can be shortened, but you still need to be patient. The
comprehensive gene analysis, the scale of the study, and the expected high quality of the analysis mean that there is no need to rush. After the report is generated,
you should add a few more days to provide the doctor with the full data. The doctor will inform you about the results and consult them.

What should I do to have my child tested with the Nova test?

You should contact a doctor who works with the Nova test (e.g. by asking your pediatrician, geneticist or neonatologist). If you do not have the contact details of such a doctor, please contact us by sending information to contact@pti-ls.com that you express your willingness to perform the Nova test together including your email address and telephone number. We will call you back or write back. The administrator of your personal data will be PTI Life Sciences sp. z o. o.

The list of doctors who work with Nova is not publicly available (we are trying to change this), however, after you contact us, we are able to suggest a specialist who
will help you with the test. Please note that the Nova test is a new offer on the market, so it will not be available in every region of Poland immediately. The list of
doctors working with Nova will grow over time.

Our concern for the quality of services provided means that we provide doctors with comprehensive information about the Nova test, so that both the doctor and the
patient they consult feel comfortable with the knowledge they have acquired on this subject.

Does a repeat test mean my child may have a disease?

No. There may be other reasons why a repeat test is necessary. This could be due to incorrect placement of the blood on the absorption paper, damage, or poor quality of the sample. In such cases, simply take another blood sample as soon as possible.

What if my child has one of these conditions?

First of all, a positive screening test result does not predetermine the disease. The child can only be a carrier, and the disease does not necessarily have to appear. However, if it turns out that the risk associated with a given mutation suggests the possibility of a disease, a genetic consultation with a specialist and additional diagnostic tests for the disease will be recommended. It is worth remembering that the results of tests conducted as part of screening tests do not constitute a diagnosis. They only require referring the patient for further, more advanced and specialized tests.

All diseases listed in the test are subject to treatment, which can alleviate their effects. If treatment is started early enough, symptoms can be completely prevented or alleviated, improving the quality of life. Early treatment cannot completely prevent the effects of all diseases, but it can allow the child to develop normally. Medical care should be coordinated by a doctor who specializes in the disease in question.

My child is sick. Will my future children have this disease too?

It depends on the disease and the mutated gene. All diseases in the Nova test are genetic and are inherited by children from their parents. A positive screening result does not necessarily mean that subsequent children will also have the disease, just as a negative result does not guarantee that subsequent children will be healthy.

Carriers have one gene mutation but are healthy. Children and their parents can be carriers even though no one in their family has had the disease. It is worth seeking genetic counseling to better understand how the child got the disease and to learn about the risks of the disease and being a carrier for their future children and other family members.

What are the contraindications to performing the test?

The Nova test should not be performed on children who have undergone an allogeneic transplant, i.e. the donor and recipient are different people (NB an autologous transplant, i.e. the donor is also the recipient, does not disqualify the test). If the person being tested has experienced any other situation that could have led to the presence of another person’s DNA in their blood, the test results may be inaccurate. In the case of a blood transfusion, the waiting period before performing the test should be at least 6 months.

It is not recommended to perform these tests on clinical patients or on infants in the neonatal intensive care unit (NICU).
This test is also not performed for the clinical confirmation of any genetic disease. It is important to remember that the screening tests offered have a defined and limited scope in terms of the diseases and genes they can detect and analyze. These are pathogenic and suspected pathogenic gene variants that have been included in the current version of the database of hereditary diseases of newborns. If the patient wants to determine the cause of a specific disease through genetic testing, it is recommended to perform chromosomal or whole exome sequencing studies that correspond to the clinically suspected disease.

Before performing the examination, the doctor will conduct an interview and assess whether there are any contraindications.

List of conditions

AR – autosomal recessive	XLR – X-linked recessive	XL – XLR or XLD
AD – autosomal dominant	XLD – X-linked dominant	Mi – Mitochondrial

#	Disease categories	Condition name	Gene	Type
1	Hyperphenylalaninemia	Phenylketonuria	PAH	AR
		BH4-Deficient Hyperphenylalaninemia A	PTS	AR
		BH4-Deficient Hyperphenylalaninemia B	GCH1	AR
		BH4-Deficient Hyperphenylalaninemia C	QDPR	AR
		BH4-Deficient Hyperphenylalaninemia D	PCBD1	AR
		Mild non-BH4-deficient Hyperphenylalaninemia	DNAJC12	AR
1	Carbamoylphosphate Synthetase Deficiency	Carbamoylphosphate Synthetase I Deficiency	CPS1	AR
2	Maple Syrup Urine Disease	Maple Syrup Urine Disease,type Ia	BCKDHA	AR
		Maple Syrup Urine Disease,type Ib	BCKDHB	AR
		Maple Syrup Urine Disease,type II	DBT	AR
		Mild Variant Maple Syrup Urine Disease	PPM1K	AR
3	Glycine Encephalopathy	Glycine Encephalopathy	AMT	AR
		Glycine Encephalopathy	GLDC	AR
		Glycine Encephalopathy	GCSH	AR
4	Hypermethioninemia	Hypermethioninemia	MAT1A	AR
		Hypermethioninemia with S-Adenosylhomocysteine Hydrolase Deficiency	AHCY	AR
		Hypermethioninemia due to Adenosine Kinase Deficiency	ADK	AR
		Glycine N-Methyltransferase Deficiency	GNMT	AR
5	Hyperornithinemia- Hyperammonemia- Homocitrullinuria Syndrome	Hyperornithinemia-Hyperammonemia- Homocitrullinuria Syndrome	SLC25A15	AR
6	Hyperprolinemia	Hyperprolinemia Type I	PRODH	AR
6	Hyperprolinemia	Hyperprolinemia Type II	ALDH4A1	AR
7	Homocystinuria	Homocystinuria Due to Cystathionine Beta-Synthase Deficiency	CBS	AR
		Homocystinuria Due to MTHFR Deficiency	MTHFR	AR
		Homocystinuria-Megaloblastic Anemia CblG type	MTR	AR
		Homocystinuria-Megaloblastic Anemia CblE type	MTRR	AR
8	Citrullinemia	Citrullinemia, Type II, Neonatal-Onset	SLC25A13	AR
8	Citrullinemia	Citrullinemia, Type I	ASS1	AR
9	Argininosuccinic Aciduria	Argininosuccinic Aciduria	ASL	AR
10	Argininemia	Argininemia	ARG1	AR
11	Tyrosinemia Type	Tyrosinemia Type I	FAH	AR
		Tyrosinemia Type II	TAT	AR
		Tyrosinemia Type III	HPD	AR
12	Ornithine Transcarbamylase Deficiency	Ornithine Transcarbamylase Deficiency	OTC	XL
13	N-acetylglutamate Synthase Deficiency	N-Acetylglutamate Synthase Deficiency	NAGS	AR
14	Hypervalinemia	Hypervalinemia	BCAT1	AR
14	Hypervalinemia	Hypervalinemia	BCAT2	AR
15	Histidinemia	Histidinemia	HAL	AD, AR
16	2-Methylbutyryl Glycinuria	2-Methylbutyryl Glycinuria	ACADSB	AR
17	3-Methylcrotonyl-CoA Carboxylase Deficiency	3-Methylcrotonyl-CoA Carboxylase 1 Deficiency	MCCC1	AR
17	3-Methylcrotonyl-CoA Carboxylase Deficiency	3-Methylcrotonyl-CoA Carboxylase 2 Deficiency	MCCC2	AR
18	3-Methylglutaconic Aciduria	3-Methylglutaconic Aciduria Type 1	AUH	AR
		3-Methylglutaconic Aciduria Type 2 (Barth syndrome)	TAFAZZIN	XLR
		3-Methylglutaconic Aciduria Type 3	OPA3	AR
		3-Methylglutaconic Aciduria Type 5	DNAJC19	AR
		3-Methylglutaconic Aciduria Type 7B	CLPB	AR
		3-Methylglutaconic Aciduria with Deafness, Encephalopathy, and Leigh-like Syndrome	SERAC1	AR
19	3-hydroxy-3-methylglutaryl-CoA Lyase Deficiency	3-Hydroxy-3-Methylglutaryl-CoA Lyase Deficiency	HMGCL	AR
20	3-Hydroxy-3- Methylglutaryl-CoA Synthase 2 Deficiency	3-Hydroxy-3-Methylglutaryl-CoA Synthase 2 Deficiency	HMGCS2	AR
21	Beta-Ketothiolase Deficiency	Beta-Ketothiolase Deficiency	ACAT1	AR
22	Malonyl-Coa Decarboxylase Deficiency (Malonic aciduria)	Malonyl-Coa Decarboxylase Deficiency (Malonic aciduria)	MLYCD	AR
23	Propionic Acidemia	Propionic Acidemia	PCCA	AR
23	Propionic Acidemia	Propionic Acidemia	PCCB	AR
24	Succinic Semialdehyde Dehydrogenase Deficiency	Succinic Semialdehyde Dehydrogenase Deficiency	ALDH5A1	AR
25	Methylmalonic Acidemia	Methylmalonic Aciduria, mut (0) Type	MMUT	AR
		Methylmalonyl-Coa Epimerase Deficiency	MCEE	AR
		Methylmalonic Acidemia, CblA Type	MMAA	AR
		Methylmalonic Acidemia, CblB Type	MMAB	AR
		Methylmalonic Aciduria and Homocystinuria CblC Type	MMACHC	AR
		Methylmalonic Aciduria and Homocystinuria CblD Type	MMADHC	AR
		Methylmalonic Aciduria and Homocystinuria CblC Type	PRDX1	AR
		Methylmalonic Aciduria and Homocystinuria, cblJ Type	ABCD4	AR
		Methylmalonic Acidemia with Homocystinuria CblX Type	HCFC1	XLR
		Methylmalonic Aciduria and Homocystinuria CblF Type	LMBRD1	AR
		Combined Malonic and Methylmalonic Aciduria	ACSF3	AR
		Methylmalonic Aciduria due to Transcobalamin Receptor Defect	CD320	AR
		Mitochondrial DNA Depletion Syndrome 5 (with methylmalonic aciduria)	SUCLA2	AR
		Mitochondrial DNA Depletion Syndrome 9 (with methylmalonic aciduria)	SUCLG1	AR
26	Multiple Carboxylase Deficiency (Holocarboxylase synthetase deficiency)	Multiple Carboxylase Deficiency (Holocarboxylase synthetase deficiency)	HLCS	AR
27	Biotinidase Deficiency	Biotinidase Deficiency	BTD	AR
28	Glutaric Acidemia I	Glutaric Acidemia I	GCDH	AR
29	2-Methyl-3- Hydroxybutyryl-CoA Dehydrogenase Deficiency (HSD10 disease) (2-methyl-3-hydroxybutyric aciduria)	2-Methyl-3- Hydroxybutyryl-CoA Dehydrogenase Deficiency (HSD10 disease) (2-methyl-3-hydroxybutyric aciduria)	HSD17B10	XLD
30	Isobutyryl-CoA Dehydrogenase Deficiency	Isobutyryl-CoA Dehydrogenase Deficiency	ACAD8	AR
31	Isovaleric Acidemia	Isovaleric Acidemia	IVD	AR
32	2,4-Dienoyl-CoA Reductase Deficiency	2,4-Dienoyl-CoA Reductase Deficiency	NADK2	AR
33	Short Chain Acyl-CoA Dehydrogenase Deficiency	Short Chain Acyl-CoA Dehydrogenase Deficiency	ACADS	AR
34	Glutaric Acidemia II	Glutaric Acidemia IIA	ETFA	AR
		Glutaric Acidemia IIB	ETFB	AR
		Glutaric Acidemia IIC	ETFDH	AR
35	Acyl-CoA Dehydrogenase Deficiency, Very Long-Chain	Acyl-CoA Dehydrogenase Deficiency, Very Long-Chain	ACADVL	AR
36	Carnitine-Acylcarnitine Translocase Deficiency	Carnitine-Acylcarnitine Translocase Deficiency	SLC25A20	AR
37	Carnitine Palmitoyl Transferase Deficiency	Carnitine Palmitoyl Transferase I Deficiency	CPT1A	AR
37	Carnitine Palmitoyl Transferase Deficiency	Carnitine Palmitoyl Transferase II Deficiency	CPT2	AR
38	Trifunctional Protein Deficiency	Trifunctional Protein Deficiency	HADHA	AR
38	Trifunctional Protein Deficiency	Trifunctional Protein Deficiency	HADHB	AR
39	Primary Carnitine Deficiency	Primary Carnitine Deficiency	SLC22A5	AR
40	Long-Chain 3- Hydroxyacyl-CoA Dehydrogenase Deficiency	Long-Chain 3-Hydroxyacyl-Coa Dehydrogenase Deficiency	HADHA	AR
41	Medium-Chain Acyl- Coenzyme A Dehydrogenase Deficiency	Medium-Chain Acyl-Coenzyme A Dehydrogenase Deficiency	ACADM	AR
42	Medium chain 3- ketoacyl-CoA thiolase Deficiency	Medium Chain 3-Ketoacyl-CoA Thiolase Deficiency	ACAA1	AR
42	Medium chain 3- ketoacyl-CoA thiolase Deficiency	Medium Chain 3-Ketoacyl-CoA Thiolase Deficiency	ACAA2	AR
43	3-Hydroxyacyl-Coa Dehydrogenase Deficiency	3-Hydroxyacyl-CoA Dehydrogenase Deficiency	HADH	AR
44	Ethylmalonic Encephalopathy	Ethylmalonic Encephalopathy	ETHE1	AR
45	Krabbe Disease	Krabbe Disease	GALC	AR
46	Fabry Disease	Fabry Disease	GLA	XL
47	Niemann-Pick Disease	Niemann-Pick Disease A/B	SMPD1	AR
		Niemann-Pick Disease Type C1	NPC1	AR
		Niemann-Pick Disease Type C2	NPC2	AR
48	Mucopolysaccharidosis	Mucopolysaccharidosis Type I	IDUA	AR
		Mucopolysaccharidosis II	IDS	XLR
		Mucopolysaccharidosis Type IIIA	SGSH	AR
		Mucopolysaccharidosis Type IIIB	NAGLU	AR
		Mucopolysaccharidosis Type IIIC	HGSNAT	AR
		Mucopolysaccharidosis Type IVA	GALNS	AR
		Mucopolysaccharidosis Type IVB	GLB1	AR
		Mucopolysaccharidosis Type VI	ARSB	AR
		Mucopolysaccharidosis Type VII	GUSB	AR
		Mucopolysaccharidosis Type IX	HYAL1	AR
49	Metachromatic Leukodystrophy	Metachromatic Leukodystrophy	ARSA	AR
50	Gangliosidosis	GM1-gangliosidosis, Type I	GLB1	AR
		GM1-gangliosidosis, Type II	GLB1	AR
		GM1-gangliosidosis, Type III	GLB1	AR
		Tay-Sachs Disease	HEXA	AR
		Sandhoff Disease	HEXB	AR
		GM2-gangliosidosis, AB variant	GM2A	AR
51	Galactosemia	Galactokinase Deficiency	GALK1	AR
		Galactosemia	GALT	AR
		Epimerase Deficiency Galactosemia	GALE	AR
52	Glycogen Storage Disease	Glycogen Storage Disease Type Ia	G6PC	AR
		Glycogen Storage Disease Type Ib/Ic	SLC37A4	AR
		Glycogen Storage Disease Type II	GAA	AR
		Glycogen Storage Disease Type III	AGL	AR
		Glycogen Storage Disease Type IV	GBE1	AR
		Glycogen Storage Disease Type V	PYGM	AR
		Glycogen Storage Disease Type VI	PYGL	AR
		Glycogen Storage Disease Type IXa1	PHKA2	XLR
		Glycogen Storage Disease Type IXb	PHKB	AR
		Glycogen Storage Disease Type IXc	PHKG2	AR
		Glycogen Storage Disease Type IXd	PHKA1	XLR
		Glycogen Storage Disease Type XIV	PGM1	AR
53	Hereditary Fructose Intolerance	Hereditary Fructose Intolerance	ALDOB	AR
54	Peroxisome Biogenesis Disorder	Peroxisome Biogenesis Disorder 1A (Zellweger)	PEX1	AR
		Peroxisome Biogenesis Disorder 1B	PEX1	AR
		Peroxisome Biogenesis Disorder 3A (Zellweger)	PEX12	AR
		Peroxisome Biogenesis Disorder 3B	PEX12	AR
		Peroxisome Biogenesis Disorder 4A	PEX6	AR
		Peroxisome Biogenesis Disorder 4B	PEX6	AD, AR
		Peroxisome Biogenesis Disorder 5A	PEX2	AR
		Peroxisome Biogenesis Disorder 5B	PEX2	AR
		Peroxisome Biogenesis Disorder 6A (Zellweger)	PEX10	AR
		Peroxisome Biogenesis Disorder 6B	PEX10	AR
		Peroxisome Biogenesis Disorder 7A	PEX26	AR
		Peroxisome Biogenesis Disorder 7B	PEX26	AR
		Heimler Syndrome 1	PEX1	AR
		Heimler Syndrome 2	PEX6	AR
55	Primary Hyperoxaluria	Primary Hyperoxaluria Type I	AGXT	AR
		Primary Hyperoxaluria Type II	GRHPR	AR
		Primary Hyperoxaluria Type III	HOGA1	AR
56	Glutaric Aciduria III	Glutaric Aciduria III	SUGCT	AR
57	Sitosterolemia	Sitosterolemia 1	ABCG8	AR
57	Sitosterolemia	Sitosterolemia 2	ABCG5	AR
58	Hypercholesterolemia, Familial	Hypercholesterolemia, Familial,1	LDLR	AD, AR
59	Cerebrotendinous Xanthomatosis	Cerebrotendinous Xanthomatosis	CYP27A1	AR
60	Menkes Disease	Menkes Disease	ATP7A	XLR
61	Hypophosphatemia	X-Linked Hypophosphatemia	PHEX	XLD
62	Wilson Disease	Wilson Disease	ATP7B	AR
63	Progressive Familial Intrahepatic Cholestasis	Progressive Familial Intrahepatic Cholestasis 1	ATP8B1	AR
		Progressive Familial Intrahepatic Cholestasis 2	ABCB11	AR
		Progressive Familial Intrahepatic Cholestasis 3	ABCB4	AR
64	Glucose-6-Phosphate Dehydrogenase Deficiency	Glucose-6-Phosphate Dehydrogenase Deficiency	G6PD	XLD
65	Congenital Bile Acid Synthesis Defect	Congenital Bile Acid Synthesis Defect 1	HSD3B7	AR
66	Hypophosphatasia	Hypophosphatasia	ALPL	AR
67	Dihydrolipoamide Dehydrogenase Deficiency	Dihydrolipoamide Dehydrogenase Deficiency	DLD	AR
68	Cerebral Creatine Deficiency Syndrome	Cerebral Creatine Deficiency Syndrome 1	SLC6A8	XLR
68	Cerebral Creatine Deficiency Syndrome	Cerebral Creatine Deficiency Syndrome 2	GAMT	AR
69	Alagille Syndrome	Alagille Syndrome 1	JAG1	AD
69	Alagille Syndrome	Alagille Syndrome 2	NOTCH2	AD
70	Crigler-Najjar Syndrome	Crigler-Najjar Syndrome type 1	UGT1A1	AR
70	Crigler-Najjar Syndrome	Crigler-Najjar Syndrome type 2	UGT1A1	AR
71	Pendred Syndrome	Pendred Syndrome	SLC26A4	AR
72	Usher Syndrome	Usher Syndrome Type IB	MYO7A	AR
		Usher Syndrome Type IC	USH1C	AR
		Usher Syndrome Type IF	PCDH15	AR
		Usher Syndrome Type IIA	USH2A	AR
		Usher Syndrome Type IIC	ADGRV1	AR
73	Aminoglycoside-Induced Deafness	Maternally Inherited Hearing Impairment	MT-RNR1	Mi
74	Autosomal Recessive Deafness	Autosomal Recessive Deafness 1A	GJB2	AR
		Autosomal Recessive Deafness 3	MYO15A	AR
		Autosomal Recessive Deafness 4 with Enlarged Vestibular Aqueduct	SLC26A4	AR
		Autosomal Recessive Deafness 7	TMC1	AR
		Autosomal Recessive Deafness 8	TMPRSS3	AR
		Autosomal Recessive Deafness 9	OTOF	AR
		Autosomal Recessive Deafness 12	CDH23	AR
		Autosomal Recessive Deafness 21	TECTA	AR
		Autosomal Recessive Deafness 22	OTOA	AR
		Autosomal Recessive Deafness 23	PCDH15	AR
		Autosomal Recessive Deafness 36	ESPN	AR
		Autosomal Recessive Deafness 42	ILDR1	AR
		Autosomal Recessive Deafness 49	MARVELD2	AR
		Autosomal Recessive Deafness 63	LRTOMT	AR
75	Autosomal Dominant Deafness	Autosomal Dominant Deafness 2B	GJB3	AD
75	Autosomal Dominant Deafness	Autosomal Dominant Deafness 5	GSDME	AD
76	Waardenburg Syndrome	Waardenburg Syndrome	MITF	AD
		Waardenburg Syndrome	PAX3	AD
		Waardenburg Syndrome	SOX10	AD
77	Wiskott-Aldrich Syndrome	Wiskott-Aldrich Syndrome 1	WAS	XLR
78	X-Linked Lymphoproliferative Syndrome	X-Linked Lymphoproliferative Syndrome 1	SH2D1A	XLR
78	X-Linked Lymphoproliferative Syndrome	X-Linked Lymphoproliferative Syndrome 2	XIAP	XLR
79	X-Linked Agammaglobulinemia	X-Linked Agammaglobulinemia 1	BTK	XLR
80	Chronic Granulomatous Disease	X-linked Chronic Granulomatous Disease	CYBB	XLR
81	Severe Combined Immunodeficiency	X-Linked Severe Combined Immunodeficiency	IL2RG	XLR
		Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, NK Cell-Positive	RAG1	AR
		Severe Combined Immunodeficiency, Autosomal Recessive, T Cell-Negative, B Cell-Negative, NK Cell-Positive	RAG2	AR
		Severe Combined Immunodeficiency Due to ADA Deficiency	ADA	AR
		Severe Combined Immunodeficiency, T cell-negative, B-cell/natural killer-cell positive	IL7R	AR
		Autosomal Recessive T Cell-Negative, B Cell-Positive, NK Cell-Negative Severe Combined Immunodeficiency	JAK3	AR
82	Familial Mediterranean Fever	Familial Mediterranean Fever	MEFV	AR
83	Immunodeficiency with Hyper-IgM	Immunodeficiency with Hyper-IgM, type 1	CD40LG	XLR
84	Severe Congenital Neutropenia	Neutropenia, Severe Congenital 1, Autosomal Dominant	ELANE	AD
85	Congenital Adrenal Hyperplasia	Congenital Adrenal Hyperplasia due to 11-Beta- Hydroxylase-Deficiency	CYP11B1	AR
		Congenital Adrenal Hyperplasia due to 17-Alpha Hydroxylase Deficiency	CYP17A1	AR
		Adrenal Hyperplasia, Congenital, due to 3-Beta- Hydroxysteroid Dehydrogenase 2 Deficiency	HSD3B2	AR
		Lipoid Congenital Adrenal Hyperplasia	STAR	AR
86	Kallmann Syndrome	Hypogonadotropic Hypogonadism 1 with or without Anosmia (Kallmann Syndrome 1)	ANOS1	XLR
		Hypogonadotropic Hypogonadism 2 with or without Anosmia	FGFR1	AD
		Kallmann Syndrome 3	PROKR2	AD
		Hypogonadotropic Hypogonadism 5 with or without Anosmia	CHD7	AD
87	Congenita Adrenal Hypoplasia	X-Linked Adrenal Hypoplasia Congenita	NR0B1	XLR
88	Hypothyroidism Congenital	Thyroid Dyshormonogenesis 2A	TPO	AR
		Thyroid Dyshormonogenesis 3	TG	AR
		Thyroid Dyshormonogenesis 5	DUOXA2	AR
		Thyroid Dyshormonogenesis 6	DUOX2	AR
		Combined Pituitary Hormone Deficiency 2	PROP1	AR
		Hypothyroidism Congenital Nongoitrous 1	TSHR	AR
		Hypothyroidism Congenital Nongoitrous 2	PAX8	AD
89	Diabetes Mellitus, Permanent Neonatal	Diabetes, Permanent Neonatal 2, with or without Neurologic Features	KCNJ11	AD
89	Diabetes Mellitus, Permanent Neonatal	Diabetes Mellitus, Permanent Neonatal 3, with or without Neurologic Features	ABCC8	AD, AR
90	Familial Hyperinsulinemic Hypoglycemia	Familial Hyperinsulinemic Hypoglycemia 1	ABCC8	AD, AR
		Familial Hyperinsulinemic Hypoglycemia 2	KCNJ11	AR
		Familial Hyperinsulinemic Hypoglycemia 4	HADH	AR
		Familial Hyperinsulinemic Hypoglycemia 5	INSR	AD
91	Pyridoxine-Dependent Epilepsy	Pyridoxine-Dependent Epilepsy	ALDH7A1	AR
92	Hereditary Spastic Paraplegia	Autosomal Dominant Spastic Paraplegia 31	REEP1	AD
		Autosomal Dominant Spastic Paraplegia 3A	ATL1	AD
		Autosomal Dominant Spastic Paraplegia 4	SPAST	AD
		Autosomal Recessive Spastic Paraplegia Type 11	SPG11	AR
93	Autosomal Dominate Myotonia Congenita	Autosomal Dominate Myotonia Congenita	CLCN1	AD, AR
94	Progressive Muscular Dystrophy	Duchenne Muscular Dystrophy	DMD	XLR
95	Spinal Muscular Atrophy, Type I	Spinal Muscular Atrophy, Type I	SMN1	AR
96	Dopa-responsive Dystonia	Tyrosine Hydroxylase Deficiency	TH	AR
96	Dopa-responsive Dystonia	Dopa-Responsive Dystonia due to Sepiapterin Reductase Deficiency	SPR	AR
97	Glucose Transporter Type 1 Deficiency Syndrome	Glucose Transporter Type 1 Deficiency Syndrome	SLC2A1	AD, AR
98	Early Infantile Epileptic Encephalopathy	Early Infantile Epileptic Encephalopathy 6	SCN1A	AD
98	Early Infantile Epileptic Encephalopathy	Early Infantile Epileptic Encephalopathy 9	PCDH19	XL
99	Brown-Vialetto-Van Laere Syndrome	Brown-Vialetto-Van Laere Syndrome 1	SLC52A3	AR
99	Brown-Vialetto-Van Laere Syndrome	Brown-Vialetto-Van Laere Syndrome 2	SLC52A2	AR
100	Diamond-Blackfan Anemia	Diamond-Blackfan Anemia 10	RPS26	AD
		Diamond-Blackfan Anemia 1	RPS19	AD
		Diamond-Blackfan Anemia 7	RPL11	AD
101	Thalassemia	Alpha-Thalassemia	HBA1	AR
		Alpha-Thalassemia	HBA2	AR
		Beta-Thalassemia	HBB	AR
102	Fanconi Anemia	Fanconi Anemia, Complementation Group A	FANCA	AR
103	Familial Hemophagocytic Lymphohistiocytosis	Familial Hemophagocytic Lymphohistiocytosis 2	PRF1	AR
103	Familial Hemophagocytic Lymphohistiocytosis	Familial Hemophagocytic Lymphohistiocytosis 3	UNC13D	AR
104	Transcobalamin II Deficiency	Transcobalamin II Deficiency	TCN2	AR
105	Gitelman syndrome	Gitelman Syndrome	SLC12A3	AR
106	Leber Hereditary Optic Neuropathy	Leber Hereditary Optic Neuropathy	MT-ND4	Mi
107	Alport Syndrome	Alport Syndrome 1, X-linked	COL4A5	XLD
		Alport Syndrome, COL4A3-related	COL4A3	AD, AR
		Alport Syndrome, COL4A4-related	COL4A4	AR
108	Tuberous Sclerosis	Tuberous Sclerosis 1	TSC1	AD
108	Tuberous Sclerosis	Tuberous Sclerosis-2	TSC2	AD
109	Cystic Fibrosis	Cystic Fibrosis	CFTR	AR
110	Retinoblastoma	Retinoblastoma	RB1	AD
111	Primary Coenzyme Q10 Deficiency	Primary Coenzyme Q10 Deficiency 7	COQ4	AR