Late-onset symptomatic hyperprolactinemia in 6-pyruvoyl-tetrahydropterin synthase deficiency
Abstract Background Tetrahydrobiopterin (BH4) deficiency caused by 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is a rare disorder that is one of the major causes of hyperphenylalaninemia in Taiwan. Methods In this study, we reviewed the clinical courses of 12 adolescent and adult patients...
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| Format: | Article |
| Language: | English |
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BMC
2023-11-01
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| Series: | Orphanet Journal of Rare Diseases |
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| Online Access: | https://doi.org/10.1186/s13023-023-02963-4 |
| _version_ | 1797629984620150784 |
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| author | Rai-Hseng Hsu Ni-Chung Lee Hui-An Chen Wuh-Liang Hwu Tung-Ming Chang Yin-Hsiu Chien |
| author_facet | Rai-Hseng Hsu Ni-Chung Lee Hui-An Chen Wuh-Liang Hwu Tung-Ming Chang Yin-Hsiu Chien |
| author_sort | Rai-Hseng Hsu |
| collection | DOAJ |
| description | Abstract Background Tetrahydrobiopterin (BH4) deficiency caused by 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is a rare disorder that is one of the major causes of hyperphenylalaninemia in Taiwan. Methods In this study, we reviewed the clinical courses of 12 adolescent and adult patients (7 females and 5 males) with PTPS deficiency. Results The patients were treated shortly after diagnosis through newborn screening with a combination of BH4, levodopa/carbidopa, and 5-OH-tryptophan. Their plasma phenylalanine and tyrosine levels were well controlled, and their prolactin levels were also decreased after treatment. However, their prolactin levels gradually rose as they grew into puberty, and at a current age of 27.5 [interquartile range (IQR 7.9)] years, five of the 12 patients had either highly elevated prolactin levels (> 100 ng/mL in one male patient, normal reference values, male < 11 ng/mL, female < 17 ng/mL) or symptoms, including irregular menstruation, amenorrhea, and breast swelling (in four female patients). The dosage of levodopa in these five patients (14.3 (IQR 3.0) mg/kg/day) was slightly higher than that in the other patients (p = 0.05). Magnetic resonance imaging studies did not reveal an increase in the size of the anterior pituitary gland, although a Rathke cleft cyst was found in one patient. Two patients received cabergoline treatment, which promptly lowered prolactin levels and relieved symptoms. Conclusions Hyperprolactinemia is common in female patients with PTPS deficiency, especially after puberty. A long-acting dopamine agonist, such as cabergoline, may be a necessary adjunctive treatment for most patients with BH4 deficiency. |
| first_indexed | 2024-03-11T11:01:36Z |
| format | Article |
| id | doaj.art-d898d3715bb7457cb12fc0c21b3d1e54 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-03-11T11:01:36Z |
| publishDate | 2023-11-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-d898d3715bb7457cb12fc0c21b3d1e542023-11-12T12:29:59ZengBMCOrphanet Journal of Rare Diseases1750-11722023-11-011811710.1186/s13023-023-02963-4Late-onset symptomatic hyperprolactinemia in 6-pyruvoyl-tetrahydropterin synthase deficiencyRai-Hseng Hsu0Ni-Chung Lee1Hui-An Chen2Wuh-Liang Hwu3Tung-Ming Chang4Yin-Hsiu Chien5Department of Pediatrics, National Taiwan University HospitalDepartment of Pediatrics, National Taiwan University HospitalDepartment of Pediatrics, National Taiwan University HospitalDepartment of Pediatrics, National Taiwan University HospitalDepartment of Pediatric Neurology, Changhua Christian Children’s HospitalDepartment of Pediatrics, National Taiwan University HospitalAbstract Background Tetrahydrobiopterin (BH4) deficiency caused by 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency is a rare disorder that is one of the major causes of hyperphenylalaninemia in Taiwan. Methods In this study, we reviewed the clinical courses of 12 adolescent and adult patients (7 females and 5 males) with PTPS deficiency. Results The patients were treated shortly after diagnosis through newborn screening with a combination of BH4, levodopa/carbidopa, and 5-OH-tryptophan. Their plasma phenylalanine and tyrosine levels were well controlled, and their prolactin levels were also decreased after treatment. However, their prolactin levels gradually rose as they grew into puberty, and at a current age of 27.5 [interquartile range (IQR 7.9)] years, five of the 12 patients had either highly elevated prolactin levels (> 100 ng/mL in one male patient, normal reference values, male < 11 ng/mL, female < 17 ng/mL) or symptoms, including irregular menstruation, amenorrhea, and breast swelling (in four female patients). The dosage of levodopa in these five patients (14.3 (IQR 3.0) mg/kg/day) was slightly higher than that in the other patients (p = 0.05). Magnetic resonance imaging studies did not reveal an increase in the size of the anterior pituitary gland, although a Rathke cleft cyst was found in one patient. Two patients received cabergoline treatment, which promptly lowered prolactin levels and relieved symptoms. Conclusions Hyperprolactinemia is common in female patients with PTPS deficiency, especially after puberty. A long-acting dopamine agonist, such as cabergoline, may be a necessary adjunctive treatment for most patients with BH4 deficiency.https://doi.org/10.1186/s13023-023-02963-4Tetrahydrobiopterin deficiencyBH46-Pyruvoyl-tetrahydropterin synthase deficiencyPTPSHyperphenylalaninemiaHyperprolactinemia |
| spellingShingle | Rai-Hseng Hsu Ni-Chung Lee Hui-An Chen Wuh-Liang Hwu Tung-Ming Chang Yin-Hsiu Chien Late-onset symptomatic hyperprolactinemia in 6-pyruvoyl-tetrahydropterin synthase deficiency Orphanet Journal of Rare Diseases Tetrahydrobiopterin deficiency BH4 6-Pyruvoyl-tetrahydropterin synthase deficiency PTPS Hyperphenylalaninemia Hyperprolactinemia |
| title | Late-onset symptomatic hyperprolactinemia in 6-pyruvoyl-tetrahydropterin synthase deficiency |
| title_full | Late-onset symptomatic hyperprolactinemia in 6-pyruvoyl-tetrahydropterin synthase deficiency |
| title_fullStr | Late-onset symptomatic hyperprolactinemia in 6-pyruvoyl-tetrahydropterin synthase deficiency |
| title_full_unstemmed | Late-onset symptomatic hyperprolactinemia in 6-pyruvoyl-tetrahydropterin synthase deficiency |
| title_short | Late-onset symptomatic hyperprolactinemia in 6-pyruvoyl-tetrahydropterin synthase deficiency |
| title_sort | late onset symptomatic hyperprolactinemia in 6 pyruvoyl tetrahydropterin synthase deficiency |
| topic | Tetrahydrobiopterin deficiency BH4 6-Pyruvoyl-tetrahydropterin synthase deficiency PTPS Hyperphenylalaninemia Hyperprolactinemia |
| url | https://doi.org/10.1186/s13023-023-02963-4 |
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