Patient with Phenylketonuria and Intellectual Disability—Problem Not Always Caused Exclusively by Insufficient Metabolic Control (Coexistence of PKU and Alazami Syndrome)

Michał Patalan,Hanna Romanowska,Elżbieta Krzywińska-Zdeb,Krzysztof Bernatowicz,Maria Giżewska,Alicja Leśniak,Mieczysław Walczak

doi:10.3390/ijerph19052574

Abstract

The authors present a case report of a boy with a classical form of phenylketonuria and Alazami syndrome. The inborn error of phenylalanine metabolism was diagnosed in the neonatal period based on population new-born screening. Despite early implementation of a low-phenylalanine diet and good biochemical control, the patient developed behavioural disorders and intellectual disability. He also presented with dysmorphic features. After long and extensive attempts to establish the genetic cause of this unusual phenotype, finally, at the age of 16 the boy was diagnosed with Alazami syndrome based on whole exome sequencing. The authors discussed the problem of neuropsychological disorders in patients with phenylketonuria and described typical clinical symptoms of Alazami syndrome. It was emphasized that the presence of one monogenic disease does not exclude the coexistence of another one.

Highlights

Accepted: 16 February 2022Phenylketonuria (PKU) [MIM #261600] is the most frequent inborn error of amino acid metabolism and is related to the disruption of the phenylalanine (Phe) metabolic pathway.In Poland, the prevalence of PKU is 1 case per 8300 live births [1]
We present a case of a boy with a classical form of PKU, dysmorphic features and developmental delay, regardless of early implementation of a low-Phe diet and good biochemical control
We present a case of a 16-year-old boy with a classical form of PKU and Alazami syndrome

Summary

Introduction

Phenylketonuria (PKU) [MIM #261600] is the most frequent inborn error of amino acid metabolism and is related to the disruption of the phenylalanine (Phe) metabolic pathway. In untreated patients with PKU or those with poor metabolic control, Phe accumulating in the blood and body fluids crosses the blood–brain barrier leading to multidirectional damage of the central nervous system (CNS). Such patients present intellectual disability and other neuropsychological deficits [2]. Alazami syndrome [OMIM #615071] is an autosomal recessive developmental disorder, manifesting itself in intellectual disability, short stature and distinctive dysmorphic features [5]. We present a case of a boy with a classical form of PKU, dysmorphic features and developmental delay, regardless of early implementation of a low-Phe diet and good biochemical control. The following case details some unusual, not previously described, phenotypic presentations of Alazami syndrome

A Case Report

Discussion

Conclusions