A rare cause of hyperphenylalaninemia: four cases from a single family with DNAJC12 deficiency
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Dilek Gunes
and
Leyli Senturk
Abstract
Objectives
DNAJC12 deficiency (OMIM# 617384) is a new cause of hyperphenylalaninemia (HPA). The deficiency of the co-chaperone protein DNAJC12 was identified in 2017. To date, only 43 patients have been reported. Here, we report four patients from a single family with DNAJC12 deficiency while being followed up with a diagnosis of HPA.
Case presentation
Two of the patients, who were cousins, were diagnosed with HPA by newborn screening. And the other two patients were siblings of these patients. Neurological examinations were normal except for one patient with mild learning disability. A c.158-2A>T p.(?) biallelic pathogenic variant was detected in intron 2 of the DNAJC12 gene. In the 24 h tetrahydrobiopterin (BH4) challenge test, there was a significant decrease in phenylalanine levels, especially at the 16th hour. Three patients had decreased homovalinic acid (HVA) and 5-hydroxyindoleacetic acid (5HIAA) in cerebrospinal fluid (CSF), while only one had decreased 5HIAA. In treatment, sapropterin, levodopa/carbidopa and 5-OH tryptophan were started.
Conclusions
We propose that it will be beneficial to evaluate the patients who have unexplained hyperphenylalaninemia for DNAJC12 deficiency. Patients with early diagnosis of neurotransmitter deficiency may be given a chance to be treated before clinical symptoms begin.
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Research funding: This study did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors.
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Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
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Conflicts of interests: All authors do not have any potential, perceived or real conflicts of interest.
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Informed consent: All clinical data were obtained with written informed consent from the parents of all investigated subjects.
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Ethical approval: The study is in agreement with the Declaration of Helsinki and was approved by the Ethical Committees of the Centers participating in this study. The study was approved by the Ethics Committee of Bezmialem Vakif University Hospital (Ethics Board number2022/402).
References
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Articles in the same Issue
- Frontmatter
- Original Articles
- Metabolic risk factors in prepubertal and pubertal patients with overweight and obesity
- Blood pressure in girls with central precocious puberty receiving GnRH analogue therapy
- Norethindrone dosing for adequate menstrual suppression in adolescents
- Apparent diffusion coefficient (ADC) measurements and morphometric evaluation of the cranium in age-matched children with central precocious puberty
- Characteristics of vitamin D deficiency hypocalcemia inpatient admissions at a single tertiary center
- Early pregnancy exposure of maternal triglyceride levels and its effects on birth weight
- Evaluation of the clinical, biochemical, and genetic presentation of neonatal and adult-onset 5,10-methylene tetrahydrofolate reductase (MTHFR) deficiency in patients from Pakistan
- Congenital hypothyroidism in Bogotá, Colombia: a current description (2015–2021)
- Case Reports
- Case report: mitochondrial diabetes mellitus in a Chinese family due to m.3243A>G
- Novel pathogenic variant of DICER1 in an adolescent with multinodular goiter, ovarian Sertoli–Leydig cell tumor and pineal parenchymal tumor of intermediate differentiation
- Fibroblast growth factor 23 levels in cord and peripheral blood during early neonatal period as possible predictors of affected offspring of X-linked hypophosphatemic rickets: report of three female cases from two pedigrees
- A rare cause of hyperphenylalaninemia: four cases from a single family with DNAJC12 deficiency
- The benefit of rhGH therapy in a Chinese child with 12q14 microdeletion syndrome: a case report
- Adjustment of octreotide dose given via insulin pump based on continuous glucose monitoring (CGM) in a child with congenital hyperinsulinism
