Amino acid and carbohydrate metabolism disorders
This group includes pathologies associated with genetic defects in enzyme systems. Metabolic blockade leads to the accumulation of toxic intermediate products.
Phenylketonuria (PKU) Occurs in approximately one in 10,000 children. It is caused by a deficiency of the enzyme phenylalanine 4-hydroxylase. The amino acid phenylalanine cannot be converted into tyrosine, causing its excess to accumulate in the blood and body tissues. This is a neurotoxic condition that, without intervention, leads to severe organic CNS damage, seizures, and profound intellectual disability.
- Marker: elevated phenylalanine level.
- Treatment: a strict lifelong diet with the complete exclusion of this amino acid, which must be implemented starting from the first month of life.
Galactosemia The rarest pathology in the standard panel (about 1:20,000). The problem lies in the deficiency of enzymes that break down galactose (GALT, GALK, or GALE). Toxic galactose-1-phosphate causes an acute reaction to breast milk (containing lactose).
- Symptoms: profuse diarrhea, vomiting, rapidly progressive hypotrophy, and prolonged jaundice. Without treatment, liver failure, ascites, and hemorrhagic syndrome due to decreased prothrombin develop by 2–3 months of age, and cataracts by six months. There is a high risk of sepsis and mortality.
- Marker: total galactose level.
- Management: emergency switch to specialized dairy-free nutrition (soy, casein hydrolysates).
Endocrine disorders
Timely diagnosis of hormonal defects allows for the prescription of hormone replacement therapy and ensures normal child development.
Congenital hypothyroidism A common pathology (ranging from 1:3000 to 1:6000) associated with a partial or complete lack of thyroid hormones. The lesion can be located at the level of the thyroid gland itself (primary), the pituitary gland (secondary), or the hypothalamus (tertiary). Early clinical signs include fetal macrosomia, post-term pregnancy, edema, enlarged tongue (macroglossia), a coarse voice, and prolonged jaundice. Without hormone therapy, a pronounced delay in psychomotor and physical development occurs.
- Marker: thyroid-stimulating hormone (TSH) and thyroid hormone levels.
Congenital adrenal hyperplasia (CAH) Frequency reaches 1:10,000 – 1:15,000. In 95% of cases, the syndrome is caused by 21-hydroxylase deficiency. This enzymatic block disrupts the production of cortisol and aldosterone. In response, the pituitary gland produces large amounts of ACTH in an attempt to stimulate the adrenal glands. As a result, the reaction substrate (17-OHP) massively accumulates and androgen synthesis is activated.
- Risks: life-threatening salt-wasting crises, misassignment of sex due to virilization in girls, and future infertility.
- Marker: 17-hydroxyprogesterone (17-OHP), determined by enzyme-linked immunosorbent assay (ELISA).
Cystic fibrosis
The disease occurs with a frequency of 1:3000. The main cause is a defect in the gene encoding a specific CFTR protein. The disease causes systemic damage to exocrine glands. The main impact falls on the respiratory system and the gastrointestinal tract (pancreatic insufficiency, severe chronic bronchitis, male infertility).
The primary marker is immunoreactive trypsinogen (IRT). This indicator has high sensitivity (about 85–90%), but its specificity is low. If the IRT level remains high after a retest, the infant is referred to a geneticist by the 28th day of life for final confirmation of the diagnosis via DNA analysis.
| Disease | Diagnostic marker | Approximate frequency |
|---|---|---|
| PKU | Phenylalanine | 1:10 000 |
| Hypothyroidism | TSH / Thyroid hormones | 1:3000 – 1:6000 |
| Cystic fibrosis | IRT (immunoreactive trypsinogen) | 1:3000 |
| CAH | 17-OHP (17-hydroxyprogesterone) | 1:10 000 – 1:15 000 |
| Galactosemia | Total galactose | 1:20 000 |
To understand the pathogenesis of CAH: imagine the biochemical pathway as a river with a dam. The enzyme (21-hydroxylase) is the dam, which is closed. Water (the 17-OHP substrate) massively accumulates in front of it, and it is this excess that we see in the laboratory tests.
Class and exam questions
Why might screening for hypothyroidism be false-negative in premature infants?
In low-birth-weight (less than 2000 g) and premature newborns, the level of thyroid-stimulating hormone rises much more slowly. Because of this, the standard testing timeframe is not always informative, and they must undergo a retest at 2–4 weeks of age.
What causes a false-positive result in the cystic fibrosis test (IRT)?
The level of immunoreactive trypsinogen does not have high specificity and may increase due to severe stress in the infant. Such conditions include birth asphyxia and various intrauterine infections.
Can hypothyroidism be temporary?
Yes, a transient form of hypothyroidism exists in newborns. Most of the time, this condition is caused by the mother taking antithyroid drugs during pregnancy.
What else to study on this topic
- Mechanism of negative feedback in the pituitary-adrenal axis in 21-hydroxylase deficiency
- Differential diagnosis of primary, secondary, and tertiary congenital hypothyroidism
- Features of interpreting 17-OHP levels in premature newborns
- Clinical forms of adrenogenital syndrome: salt-wasting, virilizing, and non-classic
- Stages of complication development in galactosemia during the first months of life
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