Case Report: Hyperprolinemia type II in a child with autism spectrum disorder and ALDH4A1 gene variant in a consanguineous family.
PMID 41602883 | PMCID PMC12832875 | DOI 10.3389/fped.2025.1726800 · Frontiers in pediatrics · 2025
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.
Validated evidence
| Type | Entity | Source evidence | Confidence | Extractor |
|---|---|---|---|---|
| gene | ALDH4A1 | “Case Report: Hyperprolinemia type II in a child with autism spectrum disorder and ALDH4A1 gene variant in a consanguineous family.” | 0.98 | hgnc_dict_v1 |
| phenotype | autism spectrum disorder | “Case Report: Hyperprolinemia type II in a child with autism spectrum disorder and ALDH4A1 gene variant in a consanguineous family.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | developmental delay | “Herein, we report a case of a preschool-aged Saudi girl who was born from consanguineous parents and presented with global developmental delay.” | 0.98 | phenotype_alias_lexicon_v2 |
| phenotype | inborn error of metabolism | “Hyperprolinemia type II (HPII) is a rare inherited metabolic disorder caused by the ALDH4A1 gene variant.” | 0.93 | phenotype_alias_lexicon_v2 |
| phenotype | neurodevelopmental disorder | “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.” | 0.93 | phenotype_alias_lexicon_v2 |
| population | Saudi Arabia | “Case Report: Hyperprolinemia type II in a child with autism spectrum disorder and ALDH4A1 gene variant in a consanguineous family. Herein, we report a case of a preschool-aged Saudi girl who was born from consanguineous parents and presented with global developmental delay.” | 0.95 | saudi_context_rules_v1 |