COMBO 13 MYSTERIOUS DISEASE

Up to now, about 5000 genetic disorders/diseases are known to be inherited in a Mendelian fashion. Mainly among them are autosomal recessive mutations and X-linked disorders.

More than 80% of children with inherited diseases are born to healthy parents with no history of disease.

In particular, there are genetic disorders with extremely serious symptoms and symptoms that greatly affect the quality of life.

From there, medicine needs:

• Providing solutions to help detect health problems, especially early detection of genetic mutations that cause serious diseases, is extremely necessary.
• Help doctors provide appropriate treatment orientation for patients, thereby improving and improving the quality of life and community health.

=> At that time, the Hidden Disease Gene Screening Test (Recessive Genetic Disease) was born and developed, updated to all people.

A recessive or recessive genetic disease is a disease caused by abnormalities in both genes. Both parents must be carriers of the abnormal gene to pass it on to their children.

• Patients are carriers of both copies of the mutated gene or a male carrier of a mutated gene on the X chromosome, these individuals present with typical clinical symptoms.
• Healthy carriers are carriers of 1 copy of the mutated gene, often with no symptoms or mild clinical symptoms.

• Check each individual is a healthy carrier of the disease gene
• Assess the possibility of inheriting disease genes to children if parents carry disease genes
• Actively choose assisted reproductive solutions to eliminate disease-causing genes for the next generation
• Help doctors give appropriate treatment orientation for patients; thereby improving and improving the quality of life and community health.

• Patient is diagnosed/suspected to have one or more of the 13 diseases in the description list
• Having a close family member with one or more of the 13 illnesses on the list described
• Couples who want to be screened for pre-pregnancy or are about to get married need to undergo pre-marital screening for the best pregnancy plan.

Early detection of genetic mutations that cause serious recessive diseases

• Discovered 13 common genetic diseases in Asians
• Help doctors give appropriate treatment orientation for patients
• Assess the possibility of inheriting disease genes from parents to children
• Help choose assisted reproductive solutions to remove disease-causing genes for the next generation Pre-marital, prenatal, family history of genetic diseases

It is a test that simultaneously detects mutations in 14 genes associated with 13 inherited diseases according to the following list:

Autosomal recessive inheritance:

X-linked inheritance:

1. Sample used: 2 - 3ml whole blood (collected in EDTA tube)

2. Methods used: Amplify all exons of the genes to be investigated. Library generation and sequencing using Illumina's next-generation sequencing and chemistry systems (USA)

3. Time to return results: 15 days (excluding public holidays)

1. Pompe symptoms (PD)

Pompe disease (PD) is an inherited metabolic disorder caused by acid α-glucosidase (GAA) deficiency, resulting in glycogen accumulation in lysosomes, mainly in skeletal and cardiac muscle as well as in the nervous system. PD can be classified into two classical forms, namely infant-onset PD (IOPD) and late-onset PD (LOPD).

Prevalence: PD is estimated at 1 in 40 000 live births (varies by ethnicity and geographic region)

Cause: due to a mutation in the GAA gene on chromosome 17

Symptoms: Symptoms that appear soon after birth include: weak muscle tone, difficulty eating, slow weight gain, heart defects, shortness of breath, swollen tongue, enlarged liver, impaired liver function, loss Hearing,…

Treatment: Dietary interventions, fat-soluble vitamins, lactose-free milk and medium-chain triglycerides. Delayed treatment, especially in IOPD, will lead to significant organ damage and premature death. Prognosis is good if diagnosed and treated promptly.

2.Phenylketouria (PKU)

Phenylketouria (inability to use protein) is a disorder of the conversion of Phenylalanin (Phe) to Tyrosine (Tyr) in humans, caused by a deficiency of the enzyme phenylalanine hydroxylase. This disorder causes a deficiency of Tyrosine - an important precursor for the production of serotonin, the neurotransmitter catecholoamine, melanin and thyroid hormones.

Incidence: about 1 in 20,000 - 1 in 10,000 live births.

Cause: PAH gene mutation on chromosome 12

Clinical manifestations: normal at birth. Developmental symptoms include hyperactivity, psychosis, body odor, etc. Patients who are not detected and treated in time cannot live more than 30 years.

Treatment:

Follow a strict diet consisting of 4 main principles:

1. Exclude foods with high protein / High Phe such as meat, fish, eggs, cheese, bread, flour, nuts
2. Phe amount is measured according to individual tolerance from food sources such as potatoes and peas
3. Replace natural protein with medical protein and vitamins and minerals
4. Use very low protein foods from fruits, some vegetables, butter, oils, sugar and special foods with low protein content.   

3. Glucose metabolism disorder

This is a disease that causes a disorder in the metabolism of galactose into glucose, which prevents the child from converting this sugar into usable energy but accumulates in the blood.

Incidence: is 1/50,000- 1/30 000

Cause: Due to mutations in GALT and GALK1 . genes

Manifestations: early manifestations in the first few weeks after birth such as poor sucking or aborting, diarrhea, vomiting, coma, clinical examination reveals jaundice, subcutaneous hemorrhage, hepatomegaly, cataracts

Treatment:

- Limit complications by building a diet, foods that do not contain galactose sugar.

- Change the diet with a free-lactose nutritional formula.

- For children with cataracts caused by galactosemia, surgery is needed in severe cases.

4. Congenital hypothyroidism (Pendred syndrome)

Congenital hypothyroidism is a deficiency of thyroid hormone due to a problem with thyroid development or a disorder in thyroid hormone biosynthesis.

Incidence: about 1/4000 - 1/3000

Cause: SLC26A4 gene mutation located on chromosome 7

Clinical manifestations: little or no at birth Neonatal stage: common: decreased activity, sleep a lot, difficulty suckling, prolonged jaundice, ..

Post-infancy and early childhood:

+ Slow physical development: slow weight gain, slow height growth

+ Mentally underdeveloped: less flexible, slow to learn, leading to poorer academic performance than friends

Treatment: only recovery and normal development when detected and treated early within 2-3 weeks after birth.

Treatment with synthetic thyroid hormone

+ Untreatable disease

5. Smith-Lemi-Opitz Syndrome (SLOS)

Smith Lemli Opitz syndrome is a disease that disrupts cholesterol biosynthesis (reduces)

Incidence: about 1/60 000 - 1/20 000 live births

Cause: due to a mutation in the DHCR7 gene on chromosome 11

Manifestations:

- Mental retardation (100%)

- Microcephaly - Microcephaly (90%).

- Cleft palate, small jaw, heart defects

- Underdeveloped external genitalia in males

- Musculoskeletal deformities including extra fingers or toes or adhesions of fingers or toes

Treatment: There is no specific treatment for SLOS syndrome, mainly aimed at improving symptoms and correcting defects.

- Surgical treatment of birth defects, genitals in men

- Monitor heart, eye, neurological, neuromuscular, digestive, urinary defects

- Supplementing hormones and cholesterol

6. Congenital deafness

Incidence: from 3-4/1000 newborns to the highest 1-2/100

60% of children with bilateral congenital defects are hereditary. And the abnormality of GJB2 is the most common cause of congenital hearing loss in children.

Screening methods:

- Measurement of sound emitted from the cochlea

- Assess the negative response of the brain stem

Recommendations from the American Academy of Pediatrics:

Screening for hearing loss no later than 1 month of age to detect and intervene early to limit the impact on children's language development

Diagnosis: Single-gene genetic testing combined with CT or MRI of the temporal bone

Treatment:

- Use hearing aids

- Cochlear electrode implantation

7. Wilson's disease

It is a genetic disorder that causes the body to not be able to eliminate excess copper, leading to accumulation of copper in body tissues (liver, brain, eyes and other organs) and toxic to patients. , even life-threatening.

Incidence: frequency 1/30 000 to 1/50,000. In Vietnam, there are more than 2000 patients with this disease.

Reason:

The disease is inherited in an autosomal recessive gene. This means that in Wilson's disease, the body must receive 2 abnormal ATP7B genes (1 from the father and 1 from the mother).

In Wilson's disease, part of the gene located on chromosome 13 is inactive, (ATP7B). The gene helps control the release of copper by liver cells into the bile. However, due to a gene error that does not work, copper accumulates in liver cells, when the amount of copper is exceeded, it will spill into the blood and be deposited in other organs of the body (brain, eyes and other organs). other).

Treatment:

- Treatment of copper depletion with drugs such as D-penicillamine, Trientine

- Reduced absorption of copper salts of zinc

- Supportive treatment: vitamin E, vitamin B6 supplements, copper-restricted diet counseling, liver function support treatment and symptomatic treatment.

=> Timely diagnosis and treatment help to limit complications and improve the patient's quality of life.

8. Hypochromic white matter brain dystrophy

Leukopenia myelodysplasia (MLD) is one of a number of diseases related to lipid storage that causes a toxic accumulation of abnormal lipids that interfere with normal lipids and proteins in the myelin sheath. There are three forms of MLD: late infant, adolescent, and adult.

Incidence: about 1.4–1.8 per 100 000 live births

Cause: a mutation in the ARSA gene located on chromosome 22

Manifestations:

- Starting from 1-2 years old with unsteady gait, weakness followed by decreased muscle tone, impaired behavior, later spastic paralysis, visual atrophy.

- Rarely seizures and less redness of the skin.

- Precocious puberty: starting from 5 to 10 years old, cerebellar staggers, spastic paralysis, epilepsy, death after 10-20 years.

Treatment:

Enzyme replacement therapy (ERT)

- Bone marrow transplant (BMT)

Gene therapy by ex vivo transplantation of genetically modified hematopoietic stem cells (HSCs)

9. Citrine deficiency

Citrin deficiency is also known as jaundice, cholestasis

Incidence: 1/ 50 000 – 1/ 19 000

Cause: due to mutation in gene SLC25A13

Manifestations: jaundice, cholestasis in newborns. Children under 1 year of age with a history of low birth weight, growth restriction After 1 year of age, children have manifestations such as hypoglycemia, pancreatitis, severe fatigue, anorexia, impaired quality of life. suddenly in adulthood. Occurrence of neurological symptoms.

Treatment: Dietary interventions, fat-soluble vitamins, lactose-free milk and high triglycerides.- With appropriate treatment, symptoms usually resolve after 1 year of age, in rare cases need a liver transplant.

10. Adrenal leukoencephalopathy

Adrenal leukodystrophy is an inherited disorder that occurs mainly in men, affecting the nervous system and adrenal glands. This is the most common peroxisome genetic disease, caused by mutations in the gene on chromosome Xq28, more than 200 mutations have been isolated.

Incidence: about 1/14,000 in men.

Symptoms: Signs of the disease can appear soon after birth, in some cases, develop during childhood or adulthood. Signs and symptoms can vary, depending on the type of disease and the extent of white matter damage. However, the common symptom in all cases is an abnormal growth of the myelin sheath in the brain.

Treatment: Pay attention to a high-fat diet, eat lorepos oil. Currently, medicine has not found an effective treatment for diseases related to this genetic disorder. Studies have shown that bone marrow transplants and stem cell therapy have worked in some cases, helping to slow disease progression.

11. Deficiency of G6PD

11 million babies born each year worldwide are deficient in the enzyme G6PD.

Incidence: 2/100

The most common enzyme disease, X-linked recessive. Boys are more susceptible than girls. The enzyme G6PD is produced by red blood cells to help protect red blood cells from oxidative damage. Lack of G6PD enzyme, red blood cells will be destroyed, causing hemolytic anemia, mental and motor retardation.

Clinical manifestations: jaundice, dark urine

Diagnosis: Comprehensive clinical examinationG6PD . enzyme activity test

Treatment: Eliminate triggers

- Do not use food, foods capable of oxidizing (legumes)

- Do not use drugs, foods that cause hemolysis

- The mother must also follow the G6PD deficiency diet.

12. Fabry's disease

Fabry disease is an inherited metabolic disorder, characterized by alpha-Galactosidase deficiency causing a number of pathological conditions such as keratosis pilaris, corneal opacities, paresthesias of the extremities, renal failure, heart failure...

Incidence: 1 in 117 000 people may be affected (women are less affected by this disease)

Cause: due to a mutation in the GLA gene that results in the enzyme unable to effectively break down the fat globotriaosylceramide. This fat builds up in the body's cells, especially the cells that line the blood vessels in the skin, and the cells in the kidneys, heart, and nervous system. Globotriaosylceramide gradually builds up to the point of damaging cells, leading to various signs and symptoms of Fabry disease.

Treatment:

- Medical: Some drugs are used to treat the symptoms of Fabry disease as follows:

+ Anticonvulsant drugs, treat numbness of hands and feet in patients: Carbamazepine, Phenytoin

+ Drugs to treat gastrointestinal symptoms: Metoclopramide

+ Drugs to stabilize the amount of alpha-Gal A enzyme to combat dysfunction: Migalastate

- Enzyme replacement therapy

13. Ornithine transcarbamylase (OTC) deficiency

Ornithine transcarbamylase (OTC) deficiency is an inherited disorder that causes ammonia to build up in the blood. Infants with the OTC form of deficiency may lack energy (lethargy) or have no desire to eat, and have poorly controlled breathing rates or body temperature. Complications from ornithine transcarbamylase deficiency can include developmental delays and intellectual disability. Progressive liver damage may also occur.

Incidence: 1/14,000 to 1/77,000 people.

Cause: A mutation in the OTC gene causes an OTC transcarbamylase deficiency.

Treatment: Assimilation and removal of nitrogen

Genetic counseling: Ornithine transcarbamylase deficiency is inherited in a recessive gene located on the X chromosome. A mother who carries the gene can pass this gene on to the next generation with a rate of 50%. Family members should be screened for early detection of OTC gene carriers or deficiencies.

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