Screening For Congenital Hypothyroidism Research Articles

What is the ideal thyroid-stimulating hormone (TSH) threshold value in congenital hypothyroidism screening? Twin study.

Congenital hypothyroidism is the most common preventable cause of intellectual disability. Therefore, the majority of developed countries have aimed to diagnose cases early through screening programs. In these screening programs, levels of thyroid-stimulating hormone (TSH) and free thyroxine are examined in dried blood spots taken between days 3 and 5 of life. While many countries accept TSH threshold value of 8 mU/L, there is still no consensus on the ideal TSH threshold value. As no twin studies on the TSH threshold value have been conducted previously, this study was planned. Eight pairs of twins were included in the study, with one of the twins having plasma TSH value ≥8 mU/L and the other <8 mU/L, measured between days 3 and 5 of life. The study aimed to investigate whether determining threshold TSH value of 8 mU/L would be beneficial by comparing somatic growth, mental development, and neuromotor development between twins. The age, gender, gestational weeks, birth weights, height, weight, and initial TSH values taken between days 3 and 5 of all cases were recorded. The patients' plasma Vitamin B12, folate, 25-OH Vitamin D, ferritin, and hemoglobin levels were measured. After that, they were evaluated by a child and adolescent psychiatry. Finally, the Denver Developmental Test was applied to the cases. There was no significant impairment in somatic growth, mental development, and neuromotor development in the long-term outcomes of cases with plasma TSH ≥ 8 mU/L compared to those with plasma TSH < 8 mU/L among the twins participating in our study.

CONGENITAL HYPOTHYROIDISM IN NEWBORN AND ASSOCIATION WITH SOCIODEMOGRAPHIC PARAMETERS AMONG NEONATE DELIVERED AT MILITARY HOSPITAL IN A CITY OF CENTRAL INDIA

Objectives: The present study aims to assess the incidence of congenital hypothyroidism (CH) among neonates in a tertiary care hospital in central India, examining its association with various sociodemographic parameters. Methods: This cross-sectional study, conducted between January and December 2022, included all live births at a tertiary care center in Jabalpur, Madhya Pradesh. Cord blood thyroid-stimulating hormone (TSH) levels were measured for all newborns as part of routine screening. Sociodemographic data, including maternal age, gestational age, birth order, and newborn sex, were collected. Universal sampling was employed, encompassing all consenting parents and their neonates. Results: Among 388 live births, TSH values ranged from 0.23 to 35.59 mIU/L, with a mean TSH of 8.76±5.92 mIU/L. Of the neonates, 95.9% had normal TSH levels, while 4.1% exhibited elevated levels. Subsequent follow-up identified CH in two neonates (5.2 per thousand live births). Analysis revealed no significant association between elevated TSH levels and maternal age or newborn sex. However, a significant association was observed with gestational age. Birth order also displayed significance, with the third birth order having a higher proportion of neonates with raised TSH levels. Conclusion: This study highlights the importance of CH screening in preventing long-term complications and the various sociodemographic factors linked to CH, such as maternal age, gestational age, and birth order.

The Relationship Between TSH and Indirect Bilirubin Levels in Neonates Suspected of Having Jaundice

Background: Congenital hypothyroidism (CH) is a condition of thyroid hormone deficiency that occurs at birth. The TSH (thyroid-stimulating hormone) test is crucial for diagnosing hypothyroidism. CH is known to cause prolonged unconjugated hyperbilirubinemia. Therefore, this study aimed to analyze the relationship between TSH and indirect bilirubin levels in neonates suspected of having jaundice. Methods: This is a non-experimental, retrospective study conducted at Lombok Dua Dua Lontar Mother and Child Hospital in Surabaya. The study involved data collection on neonates aged 2–7 days suspected of jaundice, whose TSH and indirect bilirubin levels were measured between November 2022 to April 2024. Results: Among 100 neonates, 62% were aged 2-4 days, while 38% were aged 5-7 days. The majority were male (56%), with female comprising 44%. Of the 100 neonates, only 1 (1%) had borderline TSH levels, while 99% had normal TSH levels. Hyperbilirubinemia was observed in 94% of the neonates, while 6% had normal indirect bilirubin levels. Statistical analysis using the Spearman correlation showed no significant link between TSH and indirect bilirubin levels (p = 0.802). Conclusions: While this study did not find a clear connection between TSH and indirect bilirubin levels in neonates suspected of having jaundice, one case of borderline TSH was identified. This neonate required referral to pediatric endocrinology, as untreated congenital hypothyroidism can lead to mental retardation. Despite limited research linking TSH and bilirubin levels in jaundiced neonates, routine screening for congenital hypothyroidism using TSH testing should be reconsidered. Future studies could benefit from focusing on specific causes of neonatal jaundice to help narrow down research questions in this area.

Congenital Hypothyroidism and School Achievement in Adolescence: A Population-Based Sibling Control Study

To study school achievement in grade 9 of compulsory school in children with congenital hypothyroidism (CH), both those detected by the national screening program and those with a normal screening result and thus diagnosed later. Nationwide study of children in the Swedish Medical Birth Register (n=1 547 927) from 1982 through 1997, linked to the neonatal screening CH cohort and the National School Register. Dried blood spot (DBS) samples are collected from all newborn infants, according to the neonatal screening program. Thyroid-stimulating hormone was used for CH screening. CH was defined as either having an abnormal screening result (DBS+) and treatment with levothyroxine (LT4+) or having a normal screening result but a CH diagnosis in the National Patient Register and treatment with LT4 (DBS-/ICD+/LT4+). Regression models were used to study school performance, which as measured as grade point sum and national test results. Sibling analysis also was performed to account for unmeasured familial factors. There were 448 children who were DBS+/LT4+ and 475 children who were DBS-/ICD+/LT4+. Children with CH had lower grade point sum, adjusted β=- 6.34 (95% CI -11.7 to -1.01) and adjusted β=-10.3 (95% CI -15.5 to -5.20) for those with abnormal (DBS+/LT4+) and normal screening (DBS-/ICD+/LT4+) results, respectively. CH also was associated with lower result on the national tests, especially in mathematics. These associations remained in the sibling analyses. Youth with CH had slightly lower school achievements compared with those without CH and compared with their siblings. CH children with a normal screening result, and thus diagnosed later, presented the lowest results on grade point sum and national tests.

Impact of Lowering TSH Cut-Off on Neonatal Screening for Congenital Hypothyroidism in Minas Gerais, Brazil.

A higher incidence of primary congenital hypothyroidism (CH) has been related to increased sensitivity in neonatal screening tests. The benefit of treatment in mild cases remains a topic of debate. We evaluated the impact of reducing the blood-spot TSH cut-off (b-TSH) from 10 (Group 2) to 6 mIU/L (Group 1) in a public neonatal screening program. During the study period, 40% of 123 newborns with CH (n = 162,729; incidence = 1:1323) had b-TSH between 6 and 10 mIU/L. Group 1 patients had fewer clinical signs (p = 0.02), lower serum TSH (p < 0.01), and higher free T4 (p < 0.01) compared to those in Group 2 at diagnosis. Reducing the b-TSH cut-off from 10 to 6 mIU/L increased screening sensitivity, allowing a third of diagnoses, mainly mild cases, not being missed. However, when evaluating the performances of b-TSH cut-offs (6, 7, 8, 9, and 10 mIU/L), the lower values were associated with low positive predictive values (PPVs) and unacceptable increased recall rates (0.57%) for a public health care program. A proposed strategy is to adopt a higher b-TSH cut-off in the first sample and a lower one in the subsequent samples from the same child, which yields a greater number of diagnoses with an acceptable PPV.

An insight into Indonesia's progress for newborn screening program: What is currently going on

ObjectivesIn this literature review, we describe the progress of Indonesia's NBS program (which is heavily centered on CH screening), its current pilot projects, and what lies ahead for this program. SettingSince its conception began with congenital hypothyroidism (CH) screening, Indonesia has experienced plodding progress in NBS. There is a shortage of literature discussing the history, or the lack of, and journey of NBS in Indonesia. MethodsWe searched for literature in Pubmed and Google Scholar with keywords such as “Newborn Screening, “Neonatal Screening," “Indonesia," “Asia Pacific," “Congenital Hypothyroidism," “Congenital Adrenal Hyperplasia,””Critical Congenital Heart Disease,” “Hearing Loss,” and “Inborn Error of Metabolism.” ResultsThe only mandatory and regulated NBS program in Indonesia is congenital hypothyroid (CH) screening, with some pilot projects being conducted on screening for congenital adrenal hyperplasia (CAH), critical congenital heart disease (CCHD), hearing loss, and to a lesser extent, inborn error of metabolisms (IEMs). ConclusionDespite the evidence and benefits, the government does not mandate or regulate newborn diseases such as CHD, CAH, hearing loss, and IEMs. The lack of regulation exists despite multiple pilot projects and studies showing a benefit in at least trying to screen newborns for those conditions.

Evaluation of the First Three Years of Treatment of Children with Congenital Hypothyroidism Identified through the Alberta Newborn Screening Program.

The effectiveness of newborn screening (NBS) for congenital hypothyroidism (CH) relies on timely screening, confirmation of diagnosis, and initiation and ongoing monitoring of treatment. The objective of this study was to ascertain the extent to which infants with CH have received timely and appropriate management within the first 3 years of life, following diagnosis through NBS in Alberta, Canada. Deidentified laboratory data were extracted between 1 April 2014 and 31 March 2019 from Alberta Health administrative databases for infants born in this time frame. Time to lab collection was anchored from date of birth. Timeliness was assessed as the frequency of monitoring of Thyroid Stimulating Hormone (TSH) and appropriateness as the frequency of children maintaining biochemical euthyroidism. Among 160 term infants, 95% had confirmation of diagnosis by 16 days of age. The cohort had a median of 2 (range 0-5) TSH measurements performed in the time interval from 0 to 1 month, 4 (0-12) from 1 to 6 months, 2 (0-10) from 6 to 12 months, and 7 (0-21) from 12 to 36 months. Approximately half were still biochemically hypothyroid (TSH > 7 mU/L) at 1 month of age. After becoming euthyroid, at least some period of hypo- (60%) or hyperthyroidism (TSH < 0.2 mU/L) (39%) was experienced. More work needs to be performed to discern factors contributing to prolonged periods of hypothyroidism or infrequent lab monitoring.

Newborn screening for congenital hypothyroidism and the time influence on the sampling

Newborn screening for congenital hypothyroidism and the time influence on the sampling

Neonatal Screening for Congenital Hypothyroidism: A Study Conducted in a Tertiary Care Hospital of Gujarat

Neonatal Screening for Congenital Hypothyroidism: A Study Conducted in a Tertiary Care Hospital of Gujarat

The Influence of Health Education on the Interest of TM III Pregnant Women in Screening for Congenital Hypothyroidism in Newborn Babies

Congenital hypothyroidism screening is a screening to select babies who suffer from congenital hypothyroidism from babies who are not sufferers by taking 2-3 drops of blood from the baby's heel. A preliminary study at PMB Midwife Endang in December 2023 found data on the number of normal births of 32 people who underwent congenital hypothyroidism screening with 11 people. It shows that mothers still have low interest in doing Congenital hypothyroidism screening because, on average, they do not know about Congenital hypothyroidism screening, so they are less motivated. Mothers have never been given health education about Congenital hypothyroidism screening. This study aimed to determine the influence of health education on the interest of the third semester of pregnant women in screening for congenital hypothyroidism in newborns. This study used Pre-experimental with one group pre and post-test design. The population was 36 in the third semester of pregnant women at PMB Endang Yuniyati Napitupulu in January, with a sample of 30 people taken using a total sampling technique. The instrument was a questionnaire. Data analysis used the Wilcoxon test. This study showed that before being given health education, most respondents were not interested in doing congenital hypothyroidism screening on their babies (73.3%), and after being given health education, most respondents were interested in doing Congenital hypothyroidism screening on their babies (76.7% ). There was an influence of health education on the interest of the third-semester of pregnant women in screening for congenital hypothyroidism in newborns (p-value = 0.000 &lt; ?: 0.05).

Screening T4 and TSH in Early Detection of Congenital Hypothyroidism in Newborns: What’s the Dilemma?

Untreated congenital hypothyroidism (CH) leads to intellectual disability. Newborn screening (NBS) for CH should be done on all infants. Prompt diagnosis by NBS leads to early and adequate treatment outcomes in very normal neurocognitive outcomes in adulthood. Newborn screening (NBS) for congenital hypothyroidism (CH) is one of the major achievements in preventive medicine. Most neonates born with CH have a normal appearance and no detectable physical signs. Blood spot thyroid stimulating hormone (TSH), thyroxine (T4), or both can be used for CH screening. The latter is more sensitive but not cost-effective, so screening by TSH or T4 is used in various programs worldwide. TSH screening is more specific in the diagnosis of CH. T4 screening is more sensitive in detecting newborns with rare hypothalamic-pituitary-hypothyroidism, but it’s less specific with a high frequency of false positives especially in low birth weight and premature infants. NBS alone is not sufficient to prevent adverse outcomes from CH in a pediatric population. In addition to NBS, the management of CH requires timely confirmation of the diagnosis and accurate interpretation of thyroid function testing, effective treatment, and consistent follow-up. Doctors need to consider hypothyroidism in the face of clinical symptoms, even if NBS thyroid test results are normal. When clinical symptoms and signs of hypothyroidism appear (such as large posterior fontanelles, large tongue, umbilical hernia, prolonged jaundice, constipation, lethargy, and/or hypothermia), measurement of serum thyroid hormone and free thyroxine is indicated, regardless of NBS results. So all these babies should be treated as having CH during the first 3 years of life, taking into account the risk of mental retardation. Re-evaluation after 3 years is required in such patients.

History of Neonatal Screening of Congenital Hypothyroidism in Portugal.

Congenital hypothyroidism (CH) leads to growth and development delays and is preventable with early treatment. Neonatal screening for CH was initiated in Portugal in 1981. This study examines the history of CH screening in the country. Data were obtained from annual reports and from the national database of neonatal screening laboratory. The CH screening strategy primarily relies on the thyroid-stimulating hormone (TSH), followed by total thyroxine measurement as the second tier for confirmation. The TSH cutoff started at 90 mIU/L, decreasing to the actual 10 mIU/L. The coverage of the screening program has increased rapidly; although voluntary, it reached about 90% in 6 years and became universal in 10 years. Guideline and cutoff updates led to the identification of over 200 additional cases, resulting in specific retesting protocols for preterm and very-low-birth-weight babies. The actual decision tree considers CH when TSH levels are above 40 mIU/L. Data from the CH screening also provide an indication of the iodine status of the population, which is presently indicative of iodine insufficiency. The Portuguese neonatal screening for CH is a history of success. It has rapidly and continuously adapted to changes in knowledge and has become a universal voluntary practice within a few years.

When bones deceive: Beyond skeletal dysplasia

Congenital hypothyroidism results from a partial or complete loss of thyroid function. It is the most common treatable cause of mental retardation. Thyroid hormone facilitates the growth and development of the skeleton through its direct effects on chondrocyte proliferation and differentiation and its permissive effects on the growth hormone. Due to the congenital hypothyroidism screening programs, congenital hypothyroidism is rare, and hence, other differential diagnoses are often considered in children presenting later in life with short stature and coarse facies such as storage disorders, genetic disorders, and skeletal dysplasia. This article aims to assess and discuss the value of radiology, especially plain radiography and ultrasonography in the diagnosis of congenital hypothyroidism and prevent long-term mental retardation and neurological dysfunction.

Experiences and Challenges with Congenital Hypothyroidism Newborn Screening in Indonesia: A National Cross-Sectional Survey.

The expansion of newborn screening (NBS) for congenital hypothyroidism (CH) is essential to reducing the number of preventable intellectual disabilities in children. Because of logistical issues, including geographic extremes, distinct cultures, and 4.8 million births annually, Indonesia has struggled to achieve universal NBS coverage. A national cross-sectional electronic survey was conducted to explore challenges in CH NBS. Responses from 423 healthcare professionals and program administrators across 30 provinces in Indonesia were collected. The major challenges reported were refusal from families (39.2%), newborns being discharged <24 h (38.3%), and limited availability of filter paper (35.9%). The respondents considered refusal from families to be due to fear, while others did not understand the necessity of CH NBS. The vast majority of respondents believed that parents do not have sufficient understanding regarding CH NBS (96.5%). Our study found that only 38.5% of respondents had received formal CH NBS training, with pediatric endocrinologists being the only profession in which all respondents had been trained. Concerted efforts are needed to improve the access to and availability of resources, increase the capacity for sample collection and analysis, empower healthcare professionals, and develop educational resources to promote understanding and acceptance of NBS amongst families.

Concurrent &lt;i&gt;THRB&lt;/i&gt; and &lt;i&gt;DUOX2&lt;/i&gt; variants in a patient detected via newborn screening for congenital hypothyroidism: a case of resistance to thyroid hormone

Concurrent &lt;i&gt;THRB&lt;/i&gt; and &lt;i&gt;DUOX2&lt;/i&gt; variants in a patient detected via newborn screening for congenital hypothyroidism: a case of resistance to thyroid hormone

IMPLEMENTASI PELAKSANAAN PROGRAM SKRINING HIPOTIROID KONGENITAL (SHK): LITERATURE REVIEW

Hypothyroidism has a major impact on cardiovascular, neurological, gastrointestinal function, metabolic function and growth disorders. Congenital Hypothyroidism Screening (SCH) is an effort to improve the quality of life and prevent growth and development disorders in toddlers. In implementing SHK, problems often arise, including a lack of retraining for health workers, a lack of an appropriate information technology system, a mix-up in the distribution of logistical needs, national health policy guarantees, applicable SOPs and patients who are less cooperative. The aim of this research is to study the implementation of The SHK program in various countries. The research used a literature review method, data sources were collected Through the PubMed database with the keywords Congenital Hypothyroidism. Inclusion criteria are research articles published in 2017-2023, using Indonesian and English, articles regarding the implementation of the SHK program and the research location has an SHK program. A total of 150 articles were collected, 8 articles were described. Results Most countries carry out SHK along with screening for other diseases in newborns. The success of SHK can extend The life expectancy of sufferers. Treatment side effect prevention programs are being developed in countries that have successfully implemented SHK.

Knowledge and perception on expanded newborn screening in Sri Lanka among pregnant women attending antenatal clinics in Teaching Hospital Mahamodara

Introduction: Unlike in developed countries, there is no established expanded newborn screening (eNBS) in resource-limited settings. In Sri Lanka, the Ministry of Health has adopted screening only for congenital hypothyroidism, critical congenital heart diseases and congenital deafness as a policy in all newborns. Hence, there is a requirement to assess the need for eNBS in Sri Lanka. This requires epidemiological studies of the inherited metabolic disorders (IMDs) before investment to ensure costeffectiveness of the programme and reflections on acceptance by beneficiaries.Objectives: To evaluate the pregnant women's knowledge, attitudes and willingness towards eNBS.Method: A descriptive cross-sectional study was conducted at the Mahamodara Maternity Hospital antenatal clinics, Galle, Southern Province, Sri Lanka. A convenient sample was obtained from the antenatal clinics. A pre-tested intervieweradministered questionnaire was used to assess basic socio-demographic details, knowledge and perception of eNBSResults: A total of 602 pregnant women took part in the study. The mean age was 29±5.7 years; 67% were in the 25-40-year age group; 37.2% were primigravida and 60% were in the third trimester. More than 50% of the study participants knew about the heel prick test done at birth. However, only 34.8% and 28% were aware of the screening for congenital hypothyroidism and congenital heart disease, respectively; 93.6% of mothers had not heard of the term IMD, and only seven were aware of the term eNBS. Nevertheless, more than 80% of participants were willing to screen their babies at birth for underlying IMDs, even if it is available on payment, as the current programme was free of charge to the family. Similarly, 96.2% were willing to screen their babies for incurable diseases.Conclusions: Though most women were aware of the heel prick test done at birth, only a suboptimal proportion of them was aware of the disease/s checked using the test. In addition, there was poor knowledge about the IMDs and eNBS. However, there were positive attitudes towards eNBS.

Progress of newborn screening in China.

Newborn screening (NBS) plays a significant role in reducing the risk of birth defects. NBS in China began in the early 1980s. Under the protection of laws and regulations and the leadership of the national health administration, approved screening centers in public hospitals took the responsibility for publicity, screening, diagnosis, treatment, follow-up and management of birth defects. As of 2022, 31 provinces (autonomous regions and municipalities directly under the central government) have carried out NBS for phenylketonuria, congenital hypothyroidism, and hearing loss, 23 provinces have carried out screening for glucose-6-phosphate dehydrogenase (with a screening rate of 89.24%), and 24 provinces have carried out screening for congenital adrenal cortical hyperplasia (91.45% screening rate). Over the past four decades, screening techniques have evolved from bacterial inhibition, fluorescence analysis, and tandem mass spectrometry for the detection of biochemical markers to genetic testing, which has greatly contributed to the expansion of the types of diseases screened for. The combined use of metabolomics and genomics is currently being explored. Effective management and rigorous quality control of NBS are prerequisites for improving the quality and ensuring the accuracy of screening. The Quality Management System for Newborn Screening System Network (QMS-NBS), established by the National Center for Clinical Laboratories, covers all screening centers and related blood collection agencies. The operation of the QMS-NBS allows the quality and performance of screening to be transparent and measurable, ensuring the quality and efficiency of screening. This article provides an overview of the history of NBS, especially the evolution of policies for the NBS in China, the construction of screening institutions, the number of newborns screened, the incidence rates of screened diseases, the changes in screening technology, the expansion of new diseases screened for, and the quality control of NBS. Overall, the progress in NBS in China has not only benefited from the development and standardization at the technological level, but also benefited from the construction of policies, regulations and ethics.

Newborn screening for congenital hypothyroidism, congenital adrenal hyperplasia and glucose-6-phosphate dehydrogenase deficiency in Bihar: A pressing priority in today's time.

Newborn screening (NBS) aims towards early detection of congenital disorders or prevention of intellectual and physical defects and life-threatening illness. Three disorders namely congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and glucose-6-phosphate dehydrogenase deficiency (G-6-PDD) were selected for a preliminary study for NBS. The study aimed to establish NBS in the Indian scenario that could lay a framework for future such initiatives. A screening programme was conducted at a tertiary care hospital for 1 year. All the neonates born at All India Institute of Medical Sciences (AIIMS), Patna, were screened for their blood levels of glucose-6-phosphate dehydrogenase (G-6-PD), 17-hydroxyprogesterone (17-OHP) and thyroid-stimulating hormone (TSH). Heel-prick blood samples were collected within 48-72 h of birth, and the level of these parameters was accessed by enzyme immunoassay (EIA). A total of 492 neonates were born from January 2020 to December 2020, of which 369 newborns were screened for CAH, CH and G-6-PDD. Of 369 neonates, one case (male) had an increased level of TSH, six cases (all males) had an increased level of 17-OHP and no case was found with G-6-PDD. Preliminary data on the prevalence of various genetic disorders revealed that CAH is the most prevalent disorder followed by CH in the population of Bihar. More efforts need to be undertaken to create awareness and to make screening a successful programme in India. A cost-effective nationwide screening programme is highly recommended for the detection of such cases at the earliest to avoid their future complication.

Results of neonatal screening for congenital hypothyroidism and hyperphenylalaninemia in Zhejiang province from 1999 to 2022.

To analyze the results of neonatal screening for congenital hypothyroidism (CH) and hyperphenylalaninemia (HPA) in Zhejiang province from 1999 to 2022. A total of 11 922 318 newborns were screened from September 1999 and December 2022 in Zhejiang province. The blood thyroid stimulating hormone (TSH) levels were measured by a fluorescence method and blood phenylalanine (Phe) levels were measured by fluorescence method or tandem mass spectrometry. TSH≥9 μIU/mL was considered positive for CH, while Phe>120 μmol/L and/or Phe/Tyr ratio>2.0 were considered positive for HPA. The positive newborns in screening were recalled, and the gene variations were detected by high-throughput sequencing and MassARRAY tests. The overall neonatal screening rate during 1999-2022 was 89.41% (11 922 318/13 333 929) and the screening rate was increased from 6.46% in 1999 to 100.0% in 2022. A total of 8924 cases of CH were diagnosed among screened newborns with an incidence rate of 1/1336. A total of 563 cases of HPA were diagnosed, including 508 cases of classic phenylketonuria (cPKU) and 55 cases of tetrahydrobiopterin deficiency (BH4D), with an incidence rate of 1/21 176. Ninety-seven out of 8924 cases of CH underwent genetic analysis. Gene mutations were detected in 9 CH related genes, the highest frequency mutations were found in DUOX2 gene (69.0%) with c.3329G>A (p.R1110Q) (18.2%) and c.1588A>T (p.K530X) (17.3%) as the hotspot mutations. There were 81 PAH gene variants detected in a total of 250 cases of cPKU, and c728G>A (p.R243Q) (24.4%), c.721C>T (p.R241C) (15.0%) were the hotspot mutations. Meanwhile 7 novel variants in PAH gene were detected: c.107C>A (p.S36*), c.137G>T (p.G46V), c.148A>G(p.K50E), c.285C>T (p.I95I), c.843-10delTTCC, exon4-7del and c.1066-2A>G. There were 12 PTS gene variants detected in 36 cases of BH4D, and c.259C>T (p.P87S) (31.9%) was the hotspot mutation. The incident of CH has increased from 1999 to 2022 in Zhejiang province, and it is higher than that of national and global levels; while the incidence of HPA is similar to the national average. DUOX2 gene variation is the most common in CH patients; c.728G>A (p.R243Q) is the hotspot mutation in cPKU patients, while c.259C>T (p.P87S) is the hotspot mutation in BH4D patients.