A large-scale cytogenetic study of the causes of intellectual disability (ID) in children from special schools and institutions was made in Taiwan between 1991 and 1996. The screening methods and the identification of subjects with ID consisted of both clinical evaluation (i.e. photographs, questionnaires on family, pre-, peri- and postnatal history, and hospital records, including IQ) and further laboratory studies for diagnosis (i.e. standard chromosome analysis, and if indicated, high-resolution banding, cytogenetic fragile-X study or molecular techniques). A total of 11,892 patients were enrolled in this study. After excluding the acquired causes of ID, such as infections and the sequelae of brain insults, or the well-known single-gene disorders and other multifactorial diseases, 4372 (36.8%) cumulative cases were recruited for karyotyping studies according to their phenotypes and medical records. Abnormal karyotypes were noted in 1889 children (43.2% of all selected children). Thus, the overall incidence of chromosomal aberrations in subjects with ID was estimated as 15.9%. Down's syndrome, the most common cause of ID, accounted for 82.4% of all patients with abnormal karyotypes. The causes of ID were considered to be prenatal in 55.2% (n = 6564) of cases, perinatal in 9.5% (n = 1130), postnatal in 3.3% (n = 392) and unknown in 32.0% (n = 3805) of cases. Two large groups were classified: (1) serious ID (37%), including profound, severe and moderate categories; and (2) mild ID (63%). The causes (pre-, peri- and postnatal, and unknown) in these two populations were: 70%, 10.5%, 5.4% and 14.1%, and 46.5%, 8.9%, 2.1% and 42.5%, respectively. Genetic causes accounted for 38.5% (n = 4578) of all cases in this study, including 1557 with Down's syndrome, 233 with fragile-X syndrome, 199 with other various chromosomal abnormalities (i.e. unbalanced translocation, supernumerary markers and structural rearrangements), 238 with a defined or presumed single-gene defect, and 98 with a recognized contiguous gene syndrome (Prader-Willi, 56; Angelman, 34; Williams, 5; and Kallmann, 3); 2120 cases had familial ID. Multiple anomalies of undefined pattern, but without chromosomal aberration, infantile autism, ID of normal phenotype or family history, were of the other categories. Patients with a single-gene disorder or chromosomal aberration, especially those with unbalanced translocated or rearranged chromosomes, had genetic counselling and family studies. Pre-screening with photographs and questionnaires may give a better costbenefit than blind mass cytogenetic studies for each individual with ID.

Ten cases of tetrahydrobiopterin (BH4) deficiency were identified in 1,337,490 newborns screened in a Chinese population in Taiwan. The high incidence of BH4 deficiency in the Taiwanese population may be explained by a founder effect, since all of the patients revealed 6-pyruvoyltetrahydropterin synthase gene mutations, and grouping N52S and P87S mutations together constituted 88.9% of the disease alleles. BH4 supplementation with restriction of high-protein foods gave control of plasma phenylalanine within normal range, and levodopa itself prevented seizure. However, the average intelligence quotient (IQ) score of these patients was only 76 +/- 14 (56-98). Statistically, the age of starting medication, including 5-hydroxytryptophan (5-HTP), was inversely correlated to IQ scores of these patients. We suggest the combination of BH4, levodopa and 5-HTP as the standard protocol to commence the treatment of BH4 deficiency as early as possible, although prenatal brain damage could have existed.

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BackgroundHypothalamic hamartoma (HH) is a rare intracranial disease whose manifestations include gelastic seizures and precocious puberty. The diagnosis and treatment of HH have changed substantially over the past three decades as medical care has improved. Bibliometrics can reveal the evolution and development of a scientific field.MethodsDocuments on HH were retrieved from the Web of Science Core Collection (WoSCC) database on September 8, 2022. The search terms were as follows: “hypothalamic hamartoma” or “hamartoma of the hypothalamus” or “hypothalamic hamartomas.” The types of documents were restricted to articles, case reports, and reviews. VOSviewer, CiteSpace, and the R package “bibliometrix” were used for a bibliometric analysis.ResultsA total of 667 independent documents on HH were obtained from the WoSCC database. The most common types of documents were articles (n = 498, 75%) and reviews (n = 103, 15%). The number of annual publications fluctuated but showed an upward trend overall, and the annual growth rate was 6.85%. The cumulative publication data indicated that the most influential journals in the HH field include Epilepsia, Epileptic Disorders, Child’s Nervous System, Neurosurgery, and the Journal of Neurosurgery. Kerrigan JF, Ng YT, Rekate HL, Regis J, and Kameyama S were among the most prominent authors in the field of HH, with numerous publications and citations. American research institutions, especially the Barrow Neurological Institute, occupied a pivotal position in HH research. Other countries and institutions were catching up and producing considerable research results. Research on HH has steadily switched its emphasis from Pallister-Hall syndrome (PHS) and precocious puberty to epilepsy and new diagnostic and therapeutic techniques, including Gamma Knife, laser ablation, and interstitial thermal therapy.ConclusionHH remains a special neurological disease with significant research prospects. The development of novel technologies, including MRI-guided laser-induced thermal therapy (MRg-LiTT) and stereotactic radiofrequency thermocoagulation (RF-TC), has enabled the efficient treatment of gelastic seizures in HH while minimizing the risks associated with craniotomies. Through bibliometric analysis, this study points out the direction for future HH research.