CASE REPORT article
Front. Pediatr.
Sec. Genetics of Common and Rare Diseases
Case Report: Hyperprolinemia Type II in a Child with Autism Spectrum Disorder and ALDH4A1 Gene Variant in a Consanguineous Family
Provisionally accepted
- 1King Fahd University Hospital, Imam Abdulrahman Bin Faisal University, Al Khobar, Saudi Arabia
- 2Imam Abdulrahman Bin Faisal University, Dammam, Saudi Arabia
- 32. Laboratory Medicine Department, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University, Al Khobar, Saudi Arabia, khober, Saudi Arabia
- 43. Lifera Omics, Riyadh, Saudi Arabia, Riyadh, Saudi Arabia
- 5Qatif Central Hospital, Al Qatif, Saudi Arabia
- 6Royal College of Physicians of Ireland, Dublin, Ireland
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Hyperprolinemia type II (HPII) is a rare inherited metabolic disorder caused by the ALDH4A1 gene variant. Herein, we report a case of a preschool-aged Saudi girl who was born from consanguineous parents and presented with global developmental delay. The patient was clinically diagnosed with autism spectrum disorder with associated disruptive behaviors. Metabolic investigations revealed markedly elevated plasma and urinary proline levels, suggestive of a proline metabolism disorder. Whole-exome sequencing identified a homozygous variant of uncertain significance in the ALDH4A1 gene, which is associated with autosomal recessive HPII. Genetic testing of the patient's family members showed that all individuals had carrier status with varying zygosity. This case underscores the importance of metabolic and genetic evaluation in children with neurodevelopmental disorders and highlights that HPII can present with a clinical phenotype that overlaps substantially with ASD.
Keywords: ALDH4A14, Autism Spectrum Disorders 3, Global developmental delay5, hyperprolinemia type 22, Hyperprolinemia type II 1, proline6
Received: 16 Oct 2025; Accepted: 19 Dec 2025.
Copyright: © 2025 AlQurashi, Al-Awam, Alhaddad and Alrebh. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Faisal AlQurashi
Zahra A. Alrebh
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